Rahul Banerjee

Immune effector cell-associated hematotoxicity (ICAHT) is associated with morbidity and mortality after chimeric antigen receptor (CAR) T-cell therapy. To date, the factors associated with ICAHT are poorly characterized, and there is no validated predictive model of ICAHT specifically. We trained (n = 483) and validated (n = 208) two Early ICAHT Prediction Models (eIPM): eIPMPre including pre-infusion factors only (disease type and pre-LD ANC, platelet count, LDH, and ferritin) and eIPMPost… Show more

Immune effector cell-associated hematotoxicity (ICAHT) is associated with morbidity and mortality after chimeric antigen receptor (CAR) T-cell therapy. To date, the factors associated with ICAHT are poorly characterized, and there is no validated predictive model of ICAHT specifically. We trained (n = 483) and validated (n = 208) two Early ICAHT Prediction Models (eIPM): eIPMPre including pre-infusion factors only (disease type and pre-LD ANC, platelet count, LDH, and ferritin) and eIPMPost containing both pre- (disease type and pre-LD ANC, platelet count, and LDH) and post-infusion (day +3 ferritin) factors. Both models generated calibrated predictions and high discrimination. Show less

We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% for ciltacabtagene autoleucel). IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy typically beginning 1-3 months after infusion. Thorough diagnostic workup is essential, including evaluation for potential T-cell malignancies. The early use… Show more

We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% for ciltacabtagene autoleucel). IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy typically beginning 1-3 months after infusion. Thorough diagnostic workup is essential, including evaluation for potential T-cell malignancies. The early use of infliximab or vedolizumab may potentially hasten symptom resolution and lower reliance on high-dose corticosteroids during the post-CAR-T period. Show less

The innovative pilot study herein demonstrates the practicality of integrating smartwatch-derived biometric data into provider-facing platforms including the institutional electronic medical record during radiation therapy. The first step toward integrating these data into routine clinical decision making is making sure that these data can be integrated into routine clinical decision making: namely, by accurate transmission of biometric information into a medium and format that clinicians can… Show more

The innovative pilot study herein demonstrates the practicality of integrating smartwatch-derived biometric data into provider-facing platforms including the institutional electronic medical record during radiation therapy. The first step toward integrating these data into routine clinical decision making is making sure that these data can be integrated into routine clinical decision making: namely, by accurate transmission of biometric information into a medium and format that clinicians can (and would) readily access. This approach is clearly feasible, and more work in coming years will solidify the role of this technology along PS determinations and traditional VS measurements as key components of longitudinal cancer care. Show less

Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM) despite common toxicities including hyperglycemia and insomnia. We conducted a secondary pooled analysis of the S0777 and S1211 SWOG studies of NDMM, with patients categorized as FD-DEX (full-dose dexamethasone maintained throughout induction) or LD-DEX (lowered-dose dexamethasone or discontinuation; only permitted for Grade 3+ toxicities per both study protocols). Of 541 evaluated patients, the LD-DEX… Show more

Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM) despite common toxicities including hyperglycemia and insomnia. We conducted a secondary pooled analysis of the S0777 and S1211 SWOG studies of NDMM, with patients categorized as FD-DEX (full-dose dexamethasone maintained throughout induction) or LD-DEX (lowered-dose dexamethasone or discontinuation; only permitted for Grade 3+ toxicities per both study protocols). Of 541 evaluated patients, the LD-DEX group comprised 373 patients (69%). There was no difference in PFS or OS between the FD-DEX or LD-DEX groups, which were balanced in terms of age, stage, and performance status. Given dexamethasone's many toxicities and unclear benefit in the era of modern treatment regimens, dexamethasone dose reduction during NDMM induction warrants further prospective study. Show less

Many studies have documented racial, socioeconomic, geographic, and other disparities for United States patients with multiple myeloma pertaining to diagnosis and frontline management. In contrast, very little is known about disparities in the management of relapsed/refractory multiple myeloma (RRMM) despite a plethora of novel treatment options. In this review, we discuss the manifestations of disparities in RRMM and strategies to mitigate their impact. We discuss the rationales and evidence… Show more

Many studies have documented racial, socioeconomic, geographic, and other disparities for United States patients with multiple myeloma pertaining to diagnosis and frontline management. In contrast, very little is known about disparities in the management of relapsed/refractory multiple myeloma (RRMM) despite a plethora of novel treatment options. In this review, we discuss the manifestations of disparities in RRMM and strategies to mitigate their impact. We discuss the rationales and evidence base for several solutions aimed at mitigating these disparities: for example, (1) bidirectional co-management with community-based oncologists, (2) screening for risk factors based on social determinants of health, (3) strategies to build patient trust with regard to clinical trials, and (4) longitudinal access to a primary care provider. As the treatment landscape for RRMM continues to expand, these types of efforts by the field will help ensure that this landscape is equally accessible and traversable for all US patients. Show less

Intensive chemomobilization (ICM) can be used as a salvage regimen for stem cell collection ahead of autologous peripheral blood stem cell transplantation (ASCT) in multiple myeloma. In our single-center retrospective study, ICM was associated with significantly improved event-free survival but not improved overall survival compared to standard stem cell collection. ICM was associated with longer post-ASCT inpatient duration and bacteremia. Our findings suggest that ICM could be considered for… Show more

Intensive chemomobilization (ICM) can be used as a salvage regimen for stem cell collection ahead of autologous peripheral blood stem cell transplantation (ASCT) in multiple myeloma. In our single-center retrospective study, ICM was associated with significantly improved event-free survival but not improved overall survival compared to standard stem cell collection. ICM was associated with longer post-ASCT inpatient duration and bacteremia. Our findings suggest that ICM could be considered for a subset of MM patients, but its use must be weighed carefully against additional toxicity. Show less

We present a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome who had a dramatic and sustained elevation in plasma vascular endothelial growth factor (VEGF) levels from 182 to 740 pg/mL while on lenalidomide‐dexamethasone therapy. Given his biochemical evidence of progression, second‐line daratumumab was added. In hindsight, a concurrent influenza A infection was the likely driver of his VEGF elevation rather than his underlying… Show more

We present a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome who had a dramatic and sustained elevation in plasma vascular endothelial growth factor (VEGF) levels from 182 to 740 pg/mL while on lenalidomide‐dexamethasone therapy. Given his biochemical evidence of progression, second‐line daratumumab was added. In hindsight, a concurrent influenza A infection was the likely driver of his VEGF elevation rather than his underlying POEMS syndrome. Given the importance of longitudinal VEGF monitoring and the infectious risks of plasma cell therapies, our case highlights the need for caution with POEMS response assessments in the setting of a respiratory viral infection. Show less

Patients with multiple myeloma (MM) can be on therapy for years, which may lead to financial toxicity (FinTox) or time toxicity (TimeTox). We conducted a single-center cross-sectional survey of patients with MM who had undergone transplantation. Of 252 patients, 22% and 40% met FinTox+ and TimeTox+ criteria respectively. Respective FinTox+ and TimeTox+ proportions were 22%/37% for patients on maintenance, 22%/82% with active therapy, and 20%/14% with observation. FinTox+ was associated with a… Show more

Patients with multiple myeloma (MM) can be on therapy for years, which may lead to financial toxicity (FinTox) or time toxicity (TimeTox). We conducted a single-center cross-sectional survey of patients with MM who had undergone transplantation. Of 252 patients, 22% and 40% met FinTox+ and TimeTox+ criteria respectively. Respective FinTox+ and TimeTox+ proportions were 22%/37% for patients on maintenance, 22%/82% with active therapy, and 20%/14% with observation. FinTox+ was associated with a clinically meaningful decrease in mental quality of life, while TimeTox+ patients were more likely to have poor functional status. In our large study, monetary status but not disease status predicted FinTox. Over a third of patients on maintenance reported TimeTox. These two toxicities may negatively impact patient wellbeing, and studies of strategies to mitigate their impact are in development. Show less

Perspectives regarding potential barriers for multiple myeloma (MM) cellular therapy from referring-center oncologists (ROs) versus treating-center oncologists (TOs) have not been reported. In our survey of ROs and TOs, the top RO-stated barrier to CAR-T was financial toxicity while the top TO-stated barrier to CAR-T was leukapheresis/manufacturing slot availability. The top RO-stated barrier to T-cell engagers (TCEs) was financial toxicity, while the top TO-stated barrier to TCE was the… Show more

Perspectives regarding potential barriers for multiple myeloma (MM) cellular therapy from referring-center oncologists (ROs) versus treating-center oncologists (TOs) have not been reported. In our survey of ROs and TOs, the top RO-stated barrier to CAR-T was financial toxicity while the top TO-stated barrier to CAR-T was leukapheresis/manufacturing slot availability. The top RO-stated barrier to T-cell engagers (TCEs) was financial toxicity, while the top TO-stated barrier to TCE was the hospitalization requirement. Interventions to lower financial toxicity during these therapies, and outreach to raise awareness of such interventions among ROs, are needed alongside strategies to streamline manufacturing (for CAR-T) and monitoring. Show less

In this issue of Blood, Touzeau et al report the results of the phase 2 IFM 2018-04 trial of quadruplet induction and double autologous stem cell transplantation (ASCT) in patients with high-risk (HR) multiple myeloma (MM). Their study demonstrates the feasibility of quadruplet therapy in HR MM and the staying power of double ASCT as an option in these scenarios. We are fortunate as a field to have a growing collection of footwear with which to stamp out HR MM. Even if prolonged induction and… Show more

In this issue of Blood, Touzeau et al report the results of the phase 2 IFM 2018-04 trial of quadruplet induction and double autologous stem cell transplantation (ASCT) in patients with high-risk (HR) multiple myeloma (MM). Their study demonstrates the feasibility of quadruplet therapy in HR MM and the staying power of double ASCT as an option in these scenarios. We are fortunate as a field to have a growing collection of footwear with which to stamp out HR MM. Even if prolonged induction and consolidation with ASCT cannot eradicate myeloma entirely, perhaps the incorporation of chimeric antigen receptor T-cell therapies and bispecific antibodies in coming years will help us discover the best way to finally give MM the boot. Show less

The concept of time toxicity in oncology refers to the presence of frequent healthcare-related interactions that can interfere with patient well-being. In this review, we examine several manifestations of time toxicity in non-Hodgkin lymphoma and multiple myeloma and discuss their impact on decision-making with patients. We outline the challenges with measuring time toxicity as a trial endpoint but discuss its importance as a consideration for patient care, both in standard-of-care settings and… Show more

The concept of time toxicity in oncology refers to the presence of frequent healthcare-related interactions that can interfere with patient well-being. In this review, we examine several manifestations of time toxicity in non-Hodgkin lymphoma and multiple myeloma and discuss their impact on decision-making with patients. We outline the challenges with measuring time toxicity as a trial endpoint but discuss its importance as a consideration for patient care, both in standard-of-care settings and in clinical trials. Throughout the review, we highlight strategies to lower the time toxicity of therapies in lymphoma and myeloma without compromising their efficacy or patient safety. Show less

For patients with relapsed/refractory multiple myeloma with relapse following chimeric antigen receptor T-cell (CAR-T) therapies, optimal treatment strategies remain unclear. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies. Among all LOTs, high response rates were observed among those receiving another BCMA-directed CAR-T (89%), BCMA-directed bispecific antibody (BsAb) (60%)… Show more

For patients with relapsed/refractory multiple myeloma with relapse following chimeric antigen receptor T-cell (CAR-T) therapies, optimal treatment strategies remain unclear. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies. Among all LOTs, high response rates were observed among those receiving another BCMA-directed CAR-T (89%), BCMA-directed bispecific antibody (BsAb) (60%), CD38-directed combinations, and alkylator-combinations (50%). Retreatment with BCMA-directed CAR-T and BsAb can be effective salvage options post-BCMA-directed CAR-T relapse; however, durations of response appear limited and further studies are warranted. Show less

We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed multiple myeloma. Progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable between twice-weekly bortezomib (n = 910) and once-weekly bortezomib (n = 1522). Peripheral neuropathy rates were higher in patients receiving… Show more

We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed multiple myeloma. Progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable between twice-weekly bortezomib (n = 910) and once-weekly bortezomib (n = 1522). Peripheral neuropathy rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM. Show less

There are limited data on the safety and efficacy of chimeric antigen T-cell receptor (CAR-T) and bispecific antibodies (bsAb) in multiple myeloma (MM) patients with a prior history of allogeneic transplantation (allo-HCT). Thirty-three MM patients with prior allo-HCT received CAR-T (n = 24) or BsAb (n = 9) therapy. CAR-T therapy demonstrated an ORR of 92% (67% ≥ CR), while BsAb therapy resulted in an ORR of 44% (44% ≥ CR). Cytokine release syndrome (CRS) occurred in 83% of CAR-T and 78% of… Show more

There are limited data on the safety and efficacy of chimeric antigen T-cell receptor (CAR-T) and bispecific antibodies (bsAb) in multiple myeloma (MM) patients with a prior history of allogeneic transplantation (allo-HCT). Thirty-three MM patients with prior allo-HCT received CAR-T (n = 24) or BsAb (n = 9) therapy. CAR-T therapy demonstrated an ORR of 92% (67% ≥ CR), while BsAb therapy resulted in an ORR of 44% (44% ≥ CR). Cytokine release syndrome (CRS) occurred in 83% of CAR-T and 78% of BsAb recipients, while neurotoxicity was observed in three CAR-T patients. No exacerbation of graft-versus-host disease occurred except in one BsAb recipient. CAR-T and BsAb therapies appear to be feasible, safe and provide deep and durable responses in MM patients with prior allo-HCT. Show less

On November 28, 2023, the Food and Drug Administration (FDA) released a statement regarding T-cell malignancies in recipients of chimeric antigen receptor T-cell (CAR T) therapies for hematologic malignancies. The same week, an online-only abstract for the 2023 American Society of Hematology (ASH) meeting was published describing a case of T-cell lymphoma diagnosed 5 months after ciltacabtagene autoleucel (cilta-cel) for relapsed multiple myeloma. Many news organizations have already reported… Show more

On November 28, 2023, the Food and Drug Administration (FDA) released a statement regarding T-cell malignancies in recipients of chimeric antigen receptor T-cell (CAR T) therapies for hematologic malignancies. The same week, an online-only abstract for the 2023 American Society of Hematology (ASH) meeting was published describing a case of T-cell lymphoma diagnosed 5 months after ciltacabtagene autoleucel (cilta-cel) for relapsed multiple myeloma. Many news organizations have already reported on the FDA’s statement, with one headline in a leading newspaper declaring that an “Innovative Cancer Treatment May Sometimes Cause Cancer, FDA Says.” How can we best discuss the issue of second primary malignancies following CAR T therapy with our patients in light of these new updates? Show less

Since 2017, providers submitting claims for Medicare Part B drugs have been required to report how much (if any) of a single-unit vial has been discarded as part of the claims process. Bortezomib has been the costliest drug discarded annually based on these data; on average, over a quarter of each vial of bortezomib reimbursed by Medicare Part B is discarded. Why is bortezomib so heavily discarded, particularly since - compared with many other cancer drugs - it is typically only used for the… Show more

Since 2017, providers submitting claims for Medicare Part B drugs have been required to report how much (if any) of a single-unit vial has been discarded as part of the claims process. Bortezomib has been the costliest drug discarded annually based on these data; on average, over a quarter of each vial of bortezomib reimbursed by Medicare Part B is discarded. Why is bortezomib so heavily discarded, particularly since - compared with many other cancer drugs - it is typically only used for the relatively small population of patients receiving frontline therapy for multiple myeloma? As we describe, the answer lies in the mismatch between bortezomib 3.5-mg vial sizes and typical starting doses of 1.3 milligrams of meter squared body surface area. Show less

In many multiple myeloma (MM) regimens, dexamethasone (often 20–40 mg weekly) is continued alongside other anti-MM agents until progression. Despite the ubiquity of dexamethasone in MM regimens and its well-known link to eye toxicities, relatively few studies have investigated its association with ocular toxicities in MM. We analyzed patient-reported data around cataract timing and reported severity for 231 patients living with MM. Of patients who newly developed cataracts following their MM… Show more

In many multiple myeloma (MM) regimens, dexamethasone (often 20–40 mg weekly) is continued alongside other anti-MM agents until progression. Despite the ubiquity of dexamethasone in MM regimens and its well-known link to eye toxicities, relatively few studies have investigated its association with ocular toxicities in MM. We analyzed patient-reported data around cataract timing and reported severity for 231 patients living with MM. Of patients who newly developed cataracts following their MM diagnosis, over a third did so within 6 months of exposure to dexamethasone. We also found that total mg of dexamethasone exposure longitudinally - but not mg per cycle or total number of cycles - was a significant predictor of cataract severity. Our findings serve as the starting point for prospective research into the ocular health of patients with MM with an emphasis on dexamethasone dosing. Show less

Digital life coaching (DLC) may be able to address unmet needs in supportive care during transplantation for multiple myeloma (MM) through longitudinal wellness-related interactions with a certified health coach. We report the results of a single-center randomized Phase 2 trial of a 3-month DLC curriculum versus wellness-related handouts alone among patients with MM undergoing transplantation. Of 61 enrolled patients, 50 proceeded to study interventions (DLC n=21, control n=29). DLC was… Show more

Digital life coaching (DLC) may be able to address unmet needs in supportive care during transplantation for multiple myeloma (MM) through longitudinal wellness-related interactions with a certified health coach. We report the results of a single-center randomized Phase 2 trial of a 3-month DLC curriculum versus wellness-related handouts alone among patients with MM undergoing transplantation. Of 61 enrolled patients, 50 proceeded to study interventions (DLC n=21, control n=29). DLC was associated with meaningful longitudinal improvements in physical quality of life (QOL) and borderline improvements in emotional distress. For example, the percentages of patients with end-of-study distress were 10% (DLC) versus 28% (control). There were no differences in mental QOL or benzodiazepine usage. While limited by small n and uneven post-randomization study arm size, we conclude that DLC is an effective and scalable supportive care tool to support patients with MM during transplantation. Show less

While once-weekly bortezomib has been associated with similar efficacy and less neuropathy in multiple myeloma (MM), clinical trials largely continue to use twice-weekly bortezomib based on fears that regulatory agencies will not deem once-weekly bortezomib to constitute an adequate standard of care (SOC) regimen. In this study, we interviewed 217 physicians from 38 countries (spanning 6 continents) about their perceptions regarding SOC bortezomib. We found that once-weekly subcutaneous… Show more

While once-weekly bortezomib has been associated with similar efficacy and less neuropathy in multiple myeloma (MM), clinical trials largely continue to use twice-weekly bortezomib based on fears that regulatory agencies will not deem once-weekly bortezomib to constitute an adequate standard of care (SOC) regimen. In this study, we interviewed 217 physicians from 38 countries (spanning 6 continents) about their perceptions regarding SOC bortezomib. We found that once-weekly subcutaneous bortezomib was overwhelmingly preferred, with at least 90% of respondents preferring once-weekly dosing across countries and practice settings. Given the overwhelming consensus favoring once-weekly bortezomib in this peer-reviewed publication, we encourage future clinical trials to use the results of this study to justify once-weekly bortezomib as a SOC strategy to reduce peripheral neuropathy and to improve the patient experience during treatment for MM. Show less

Traditional prognostic models for newly diagnosed patients with multiple myeloma (MM), including International Staging System criteria and number of high-risk chromosomal abnormalities, are based on disease characteristics at diagnosis. However, the identification of patients at risk of more rapidly progressive MM is inherently a dynamic assessment. In a subset of patients with MM with functional high-risk MM (FHRMM), adverse disease biology only becomes evident after the failure of first-line… Show more

Traditional prognostic models for newly diagnosed patients with multiple myeloma (MM), including International Staging System criteria and number of high-risk chromosomal abnormalities, are based on disease characteristics at diagnosis. However, the identification of patients at risk of more rapidly progressive MM is inherently a dynamic assessment. In a subset of patients with MM with functional high-risk MM (FHRMM), adverse disease biology only becomes evident after the failure of first-line therapy. In this review, we explore potential definitions of FHRMM before delving into its underlying drivers based on genetic, transcriptomic, and immune cell profiling studies. We conclude our review by discussing ongoing and future studies that seek to identify and intervene upon patients with FHRMM preemptively. Show less

Purpose: Intratumoral hypoxia may interfere with chimeric antigen receptor T-cell (CAR-T) function in lymphoma. We conducted a single-center pilot study of [18F]fluoroazomycin arabinoside (FAZA) positron emission tomography (PET) imaging in this population. Only one patient demonstrated clear intratumoral hypoxia in an extranodal chest wall lesion (tumor-to-mediastinum ratio of 1.35 with regard to FAZA uptake). Interestingly, of all 16 scanned patients, he was the only patient with progressive… Show more

Purpose: Intratumoral hypoxia may interfere with chimeric antigen receptor T-cell (CAR-T) function in lymphoma. We conducted a single-center pilot study of [18F]fluoroazomycin arabinoside (FAZA) positron emission tomography (PET) imaging in this population. Only one patient demonstrated clear intratumoral hypoxia in an extranodal chest wall lesion (tumor-to-mediastinum ratio of 1.35 with regard to FAZA uptake). Interestingly, of all 16 scanned patients, he was the only patient with progressive disease within 1 month of CAR-T therapy. Our pilot study thus identified low-level FAZA uptake in a small number of patients with lymphoma receiving CAR-T therapy. Future plans include exploration of FAZA in a more selected patient population with bulky or aggressive disease. Show less

The historical rationale for moving to autologous stem cell transplantation (ASCT) after 4–6 cycles of induction in multiple myeloma (MM) is rooted in concerns about the toxicities of induction (dating back to the days of anthracycline-based therapy) or of impaired stem cell yield after prolonged lenalidomide exposure. For patients in the modern era who have achieved no better than a partial response (PR) with induction therapy, should we stay in this induction phase or should we go directly to… Show more

The historical rationale for moving to autologous stem cell transplantation (ASCT) after 4–6 cycles of induction in multiple myeloma (MM) is rooted in concerns about the toxicities of induction (dating back to the days of anthracycline-based therapy) or of impaired stem cell yield after prolonged lenalidomide exposure. For patients in the modern era who have achieved no better than a partial response (PR) with induction therapy, should we stay in this induction phase or should we go directly to ASCT? Show less

Physicians who are also parents have faced significant difficulties during the COVID-19 pandemic. However, most studies of the physician-parent workforce have focused on the experiences of attending physicians. In this commentary, we highlight the ways that trainee parents have uniquely experienced three major stressors during the pandemic: (1) childcare challenges, (2) scheduling difficulties, and (3) career uncertainties. We discuss potential solutions to mitigate these challenges for the… Show more

Physicians who are also parents have faced significant difficulties during the COVID-19 pandemic. However, most studies of the physician-parent workforce have focused on the experiences of attending physicians. In this commentary, we highlight the ways that trainee parents have uniquely experienced three major stressors during the pandemic: (1) childcare challenges, (2) scheduling difficulties, and (3) career uncertainties. We discuss potential solutions to mitigate these challenges for the future hematology/oncology workforce. As the pandemic continues, we hope that these steps can improve the ability of trainee parents to care both for their patients and their families. Show less

Patients receiving autologous chimeric antigen receptor T-cell (CAR-T) therapies for multiple myeloma may require bridging therapy (BT) before CAR-T infusion to maintain some level of disease control. There is no consensus around the optimal BT alkylator dose intensity. In our single-center retrospective analysis, we found that hyperfractionated cyclophosphamide-based regimens (HyperCy) did not result in superior disease control than weekly cyclophosphamide-based regimens (WeeklyCy) despite a… Show more

Patients receiving autologous chimeric antigen receptor T-cell (CAR-T) therapies for multiple myeloma may require bridging therapy (BT) before CAR-T infusion to maintain some level of disease control. There is no consensus around the optimal BT alkylator dose intensity. In our single-center retrospective analysis, we found that hyperfractionated cyclophosphamide-based regimens (HyperCy) did not result in superior disease control than weekly cyclophosphamide-based regimens (WeeklyCy) despite a threefold higher dose of Cy. Given the rarity of objective disease responses to chemotherapy in relapsed/refractory myeloma, our analysis suggests that hyperfractionated Cy regimens do not outperform once-weekly Cy regimens for most patients who require BT before CAR-T therapy. Show less

IMWG response criteria require refrigerated 24-hour urine specimens for most patients. However, the importance of maintaining urine testing options or requirements within each level of IMWG response criteria has not been investigated. We analyzed responses to induction therapy for all transplant-eligible patients with multiple myeloma at our institution over a 3-year period using traditional versus 'urine-free' IMWG response criteria (where references to urine were removed from the descriptions… Show more

IMWG response criteria require refrigerated 24-hour urine specimens for most patients. However, the importance of maintaining urine testing options or requirements within each level of IMWG response criteria has not been investigated. We analyzed responses to induction therapy for all transplant-eligible patients with multiple myeloma at our institution over a 3-year period using traditional versus 'urine-free' IMWG response criteria (where references to urine were removed from the descriptions for every depth of response). Of 281 evaluable patients, responses changed for only 4% of patients (95% confidence interval 2-7%) using urine-free criteria. Our results call into question the continued requirement for 24-hour urine measurements as part of IMWG response assessments for all patients. Show less

COVID-19 has been devastating for patients with cancer. In this commentary, we chronicle the pandemic's downstream impacts on United States hematology/oncology trainees in terms of professional development and career advancement. These include loss of access to clinical electives and protocol workshops, delays in research approval and execution, mentor shortages due to academic burnout, and obstacles with career transitions (most notably the post-fellowship job search). While certain silver… Show more

COVID-19 has been devastating for patients with cancer. In this commentary, we chronicle the pandemic's downstream impacts on United States hematology/oncology trainees in terms of professional development and career advancement. These include loss of access to clinical electives and protocol workshops, delays in research approval and execution, mentor shortages due to academic burnout, and obstacles with career transitions (most notably the post-fellowship job search). While certain silver linings from the pandemic have undoubtedly emerged, continued progress against COVID-19 will be essential to fully overcome the professional challenges it has created for the future hematology/oncology workforce. Show less

Recent guidelines have sought to establish clinical and research expectations for participants in blood and marrow transplantation (BMT) and cellular therapy (CT) fellowships. However, little is known about participants in BMT/CT fellowships and the value they find from this additional training. We developed a 27-item online survey addressing backgrounds, application processes, training experiences, and perceived benefits in this population. Of 105 respondents (44% pediatric trainees)… Show more

Recent guidelines have sought to establish clinical and research expectations for participants in blood and marrow transplantation (BMT) and cellular therapy (CT) fellowships. However, little is known about participants in BMT/CT fellowships and the value they find from this additional training. We developed a 27-item online survey addressing backgrounds, application processes, training experiences, and perceived benefits in this population. Of 105 respondents (44% pediatric trainees), respondents reported improved post-fellowship comfort with all queried BMT/CT-related competencies. Seventy percent of respondents stated that they would recommend their fellowship highly to others. While limited by recruitment methods and recall bias, our study demonstrated that BMT/CT fellowships are effective at increasing comfort with BMT/CT management and that most participants would highly recommend this BMT/CT training to others. Show less

The efficacy and safety of BCMA CAR-T therapy in the geriatric setting, including complications such as falls and delirium which may be more prevalent in older patients, have not been fully analyzed in patients with multiple myeloma (MM). We analyzed all patients with MM who received any autologous BCMA CAR-T therapy over a 5-year period at our institution. Our retrospective analysis did not demonstrate significant increases in CAR-T toxicity among older patients. This included toxicities… Show more

The efficacy and safety of BCMA CAR-T therapy in the geriatric setting, including complications such as falls and delirium which may be more prevalent in older patients, have not been fully analyzed in patients with multiple myeloma (MM). We analyzed all patients with MM who received any autologous BCMA CAR-T therapy over a 5-year period at our institution. Our retrospective analysis did not demonstrate significant increases in CAR-T toxicity among older patients. This included toxicities associated with geriatric populations such as falls and delirium. Overall, BCMA CAR-T remains a safe and effective option for older patients with MM. Show less

Responses to CD38-targeting monoclonal antibodies (CD38 mAbs) in multiple myeloma (MM) are not always deep or durable. Natural killer (NK) cells deficient in Fc epsilon receptor gamma subunits, known as g-NK cells, are found in higher numbers among individuals exposed to cytomegalovirus (CMV) and are able to potentiate the efficacy of daratumumab in vivo. Here, we present a single-centre, retrospective analysis of 136 patients with MM with known CMV serostatus who received a regimen containing… Show more

Responses to CD38-targeting monoclonal antibodies (CD38 mAbs) in multiple myeloma (MM) are not always deep or durable. Natural killer (NK) cells deficient in Fc epsilon receptor gamma subunits, known as g-NK cells, are found in higher numbers among individuals exposed to cytomegalovirus (CMV) and are able to potentiate the efficacy of daratumumab in vivo. Here, we present a single-centre, retrospective analysis of 136 patients with MM with known CMV serostatus who received a regimen containing a CD38 mAb. CMV seropositivity was associated with an increased overall response rate to treatment regimens containing a CD38 mAb but shorter time to treatment failure. Larger studies directly quantitating g-NK cells are required to fully understand their effect on CD38 mAb efficacy in MM. Show less

Clinical trials employing autologous transplantation followed by lenalidomide maintenance in multiple myeloma (MM) have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in MM patients following transplantation using CIBMTR registry data (n=3,948). At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%)… Show more

Clinical trials employing autologous transplantation followed by lenalidomide maintenance in multiple myeloma (MM) have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in MM patients following transplantation using CIBMTR registry data (n=3,948). At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% versus 30% and 53% versus 18%, respectively). Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT. Show less

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma. This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication.

Background: For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management. In this study of 299 patients, 35% had a dose reduction due to toxicity, 21% stopped lenalidomide due to disease progression, and… Show more

Background: For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management. In this study of 299 patients, 35% had a dose reduction due to toxicity, 21% stopped lenalidomide due to disease progression, and 19% stopped due to toxicity. Multivariate linear regression analyses did not identify any significant predictors of lenalidomide duration or discontinuation due to intolerable toxicity. Show less

Autologous chimeric antigen receptor T-cell (CAR-T) therapies targeting B-cell maturation antigen (BCMA) have revolutionized the field of multiple myeloma in the same way that the Ford Model T revolutionized the original CAR world a century ago. However, we are only beginning to understand how to improve the efficacy and usability of these cellular therapies. In this review, we explore three automotive analogies for innovation with BCMA CAR-T therapies: stronger engines, better mileage, and… Show more

Autologous chimeric antigen receptor T-cell (CAR-T) therapies targeting B-cell maturation antigen (BCMA) have revolutionized the field of multiple myeloma in the same way that the Ford Model T revolutionized the original CAR world a century ago. However, we are only beginning to understand how to improve the efficacy and usability of these cellular therapies. In this review, we explore three automotive analogies for innovation with BCMA CAR-T therapies: stronger engines, better mileage, and hassle-free delivery. Show less

In this issue of Cancer, Scordo, Shah, and colleagues report the results of their study of chemical gustometry assessments for patients with multiple myeloma receiving high-dose melphalan chemotherapy followed by autologous stem cell transplantation. Their study met its primary end point of feasibility, and the authors successfully integrated a wide range of secondary end points ranging from patient-reported outcome assessments to melphalan pharmacokinetic measurements. With all these points in… Show more

In this issue of Cancer, Scordo, Shah, and colleagues report the results of their study of chemical gustometry assessments for patients with multiple myeloma receiving high-dose melphalan chemotherapy followed by autologous stem cell transplantation. Their study met its primary end point of feasibility, and the authors successfully integrated a wide range of secondary end points ranging from patient-reported outcome assessments to melphalan pharmacokinetic measurements. With all these points in mind, how do we characterize the results of this feasibility study by Scordo, Shah,
et al.? Show less

In this issue of Bone Marrow Transplantation, Snowden et al. report the results of their exploratory study of single nucleotide polymorphisms (SNPs) and patient-reported outcomes (PROs) among patients with relapsed multiple myeloma. In this commentary, we explain why this research competes with several superhero movies for the title of “most ambitious crossover of all time.”

We report the first case of an acquired coagulopathy in a patient with isolated primary central nervous system lymphoma (PCNSL) demonstrating large-cell histology. In our patient, a paraneoplastic factor VII inhibitor significantly delayed a diagnostic lumbar puncture despite fresh frozen plasma and inactivated prothrombin complex concentrate. Our case highlights the importance of rapidly identifying and correcting paraneoplastic coagulopathies when PCNSL is suspected.

Renal dysfunction in patients with acute myeloid leukemia (AML) can be multifactorial. We present the case of a 72-year-old male with relapsed myelomonocytic AML who presented with transient acute kidney injury and severe persistent electrolyte derangements. In the setting of nephrotic-range proteinuria and electrolyte wasting without significant albuminuria or glucosuria, a diagnosis of lysozymuria was made. This represents the first case of lysozymuria presenting primarily with refractory… Show more

Renal dysfunction in patients with acute myeloid leukemia (AML) can be multifactorial. We present the case of a 72-year-old male with relapsed myelomonocytic AML who presented with transient acute kidney injury and severe persistent electrolyte derangements. In the setting of nephrotic-range proteinuria and electrolyte wasting without significant albuminuria or glucosuria, a diagnosis of lysozymuria was made. This represents the first case of lysozymuria presenting primarily with refractory electrolyte derangements rather than severe AKI. Lysozymuria portends a poor clinical prognosis even with aggressive management. Show less

POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) syndrome (a.k.a. osteosclerotic myeloma) is a paraneoplastic syndrome associated with an underlying plasma cell neoplasm. Multiple studies of autologous hematopoietic cell transplantation (autoHCT) in POEMS syndrome exist, however most are single-center experiences without data on long-term toxicity, including the risk of second primary malignancies. We report the outcomes of an international cohort of… Show more

POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) syndrome (a.k.a. osteosclerotic myeloma) is a paraneoplastic syndrome associated with an underlying plasma cell neoplasm. Multiple studies of autologous hematopoietic cell transplantation (autoHCT) in POEMS syndrome exist, however most are single-center experiences without data on long-term toxicity, including the risk of second primary malignancies. We report the outcomes of an international cohort of patients with POEMS syndrome undergoing autoHCT, emphasizing toxicities in comparison to multiple myeloma (MM) along with long-term safety and outcomes. Show less

Hematologic malignancy outcomes have remarkably improved in the past decade with further advancement expected in future years. However, the detrimental effects of financial toxicity (FT) on patients with hematologic malignancies, because of both diagnoses and subsequent treatments, have not been studied comprehensively. We performed a systematic review of all studies reporting FT as a primary or secondary outcome among adult or pediatric patients with hematological malignancies.

For patients with multiple myeloma receiving high-dose chemotherapy followed by autologous stem cell transplantation (SCT), acute life disruptions and symptom burden may lead to worsened quality of life and increased emotional distress. We investigated the feasibility of digital life coaching (DLC), whereby trained coaches deliver personalized wellbeing-related support via phone calls and text messages, as a tool to improve supportive care during this time. We found that patients and their… Show more

For patients with multiple myeloma receiving high-dose chemotherapy followed by autologous stem cell transplantation (SCT), acute life disruptions and symptom burden may lead to worsened quality of life and increased emotional distress. We investigated the feasibility of digital life coaching (DLC), whereby trained coaches deliver personalized wellbeing-related support via phone calls and text messages, as a tool to improve supportive care during this time. We found that patients and their coaches may communicate approximately once per week even while hospitalized for this intensive therapy. Based on the positive results of this pilot study, a larger phase 2 randomized study of DLC during SCT is under way to investigate its efficacy with regard to patient wellbeing. Show less

Plasma cell leukemia (PCL) is a rare but aggressive variant of multiple myeloma (MM) with a poor prognosis. Venetoclax has recently demonstrated antimyeloma activity in patients with relapsed/refractory MM carrying the t(11;14) translocation. We report the first case of a patient with relapsed/refractory PCL who achieved a complete response (with subsequent autologous stem cell transplant consolidation) with an all-oral regimen of venetoclax and dexamethasone.

Based on interim data from the randomized Phase III IKEMA study demonstrating a progression-free survival benefit with a combination of isatuximab (Isa, a CD38-targeted monoclonal antibody) and carfilzomib/dexamethasone (Kd) versus Kd alone, Isa-Kd recently received regulatory approval in the USA and Europe for patients with multiple myeloma who have received at least one prior line of therapy (in the USA, up to three prior lines). In this review we discuss the rationale and clinical trial… Show more

Based on interim data from the randomized Phase III IKEMA study demonstrating a progression-free survival benefit with a combination of isatuximab (Isa, a CD38-targeted monoclonal antibody) and carfilzomib/dexamethasone (Kd) versus Kd alone, Isa-Kd recently received regulatory approval in the USA and Europe for patients with multiple myeloma who have received at least one prior line of therapy (in the USA, up to three prior lines). In this review we discuss the rationale and clinical trial experience to date with Isa-Kd. Although final IKEMA results are pending, Isa-Kd has emerged as an effective and tolerable therapy for patients with relapsed multiple myeloma. Given the growing number of antibody-containing triplet regimens in this setting, potential niches and limitations for Isa-Kd are also discussed. Show less

For young adult patients with acute leukemia, both the efficacy and cardiotoxicity of anthracycline-based regimens have been documented. We report the case of a patient with severe cardiomyopathy, mechanically supported by a left ventricular assist device (LVAD), who subsequently developed Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph + ALL). To our knowledge, this is the first report of anthracycline administration in a patient with heart failure requiring mechanical… Show more

For young adult patients with acute leukemia, both the efficacy and cardiotoxicity of anthracycline-based regimens have been documented. We report the case of a patient with severe cardiomyopathy, mechanically supported by a left ventricular assist device (LVAD), who subsequently developed Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph + ALL). To our knowledge, this is the first report of anthracycline administration in a patient with heart failure requiring mechanical support. Show less

In multiple myeloma, a second AHCT (AHCT2) can improve progression-free survival and overall survival compared to conventional chemotherapy. Large amyloid centers have reported single-center series of patients who received AHCT2 for relapsed AL amyloidosis as well. However,
the extent to which this intervention is being utilized and its outcomes with respect to safety and long-term survival are unknown. We used the Center for International Blood and Marrow
Transplant Research database to… Show more

In multiple myeloma, a second AHCT (AHCT2) can improve progression-free survival and overall survival compared to conventional chemotherapy. Large amyloid centers have reported single-center series of patients who received AHCT2 for relapsed AL amyloidosis as well. However,
the extent to which this intervention is being utilized and its outcomes with respect to safety and long-term survival are unknown. We used the Center for International Blood and Marrow
Transplant Research database to evaluate the safety and outcomes associated with AHCT2 in relapsed/refractory AL amyloidosis. Show less

Bortezomib-based triplet regimens, specifically bortezomib, lenalidomide and dexamethasone (VRD) and bortezomib, cyclophosphamide and dexamethasone (VCD) are the two most common induction regimens used in transplant-eligible patients with newly diagnosed multiple myeloma (MM), with conflicting data on comparative efficacy and outcomes in this population. We compared long-term outcomes of MM patients receiving VRD vs. VCD induction prior to autologous stem cell transplant (ASCT).

Within the past year, several publications have compared the outcomes of clinical trials in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or R/R multiple myeloma (MM) against retrospective real-world datasets. When these observational datasets are compared against single-arm trials in such a manner, their use has been described as constituting a ‘synthetic control’ arm. However, synthetic control arms may be inadequate substitutes for true control arms generated via randomised… Show more

Within the past year, several publications have compared the outcomes of clinical trials in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or R/R multiple myeloma (MM) against retrospective real-world datasets. When these observational datasets are compared against single-arm trials in such a manner, their use has been described as constituting a ‘synthetic control’ arm. However, synthetic control arms may be inadequate substitutes for true control arms generated via randomised controlled trials. In this review, we analyze all trials using the SCHOLAR-1 and MAMMOTH datasets as synthetic control arms in lymphoma and myeloma. Show less

Accurate cancer staging is essential for determining prognosis and treatment. We used Quality Improvement (QI) methods, targeting oncology fellows, to improve fellow-seen new patient visit (NPV) staging rates by the end of the 2018-19 academic year. Monthly fellow-seen NPV staging rose from 47% in July 2018 to a mean of 75% in the first Plan-Do-Study-Act (PDSA) cycle and 70% during PDSA cycle 2. CCC-wide NPV staging rose from 6.1% to 16% during PDSA 1 and 13% during PDSA 2. Although fellows see… Show more

Accurate cancer staging is essential for determining prognosis and treatment. We used Quality Improvement (QI) methods, targeting oncology fellows, to improve fellow-seen new patient visit (NPV) staging rates by the end of the 2018-19 academic year. Monthly fellow-seen NPV staging rose from 47% in July 2018 to a mean of 75% in the first Plan-Do-Study-Act (PDSA) cycle and 70% during PDSA cycle 2. CCC-wide NPV staging rose from 6.1% to 16% during PDSA 1 and 13% during PDSA 2. Although fellows see only a minority of NPVs at our CCC, we found that our fellow-oriented QI initiative appeared to improve CCC-wide NPV staging rates as well (in the absence of any comparable initiatives). Future steps include the development of note templates with embedded staging tools to promote sustainability. Show less

The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry.

B-cell maturation antigen (BCMA) has become a key target for antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T-cell therapies, and other immunotherapies in multiple myeloma. Although BCMA has generally been considered to be expressed almost exclusively in plasma cells with a low likelihood of on-target off-tumor toxicity, there has been a range of unusual neurotoxicity observed across the spectrum of BCMA immunotherapies. Our review summarizes the literature in this… Show more

B-cell maturation antigen (BCMA) has become a key target for antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T-cell therapies, and other immunotherapies in multiple myeloma. Although BCMA has generally been considered to be expressed almost exclusively in plasma cells with a low likelihood of on-target off-tumor toxicity, there has been a range of unusual neurotoxicity observed across the spectrum of BCMA immunotherapies. Our review summarizes the literature in this field and highlights the possibility of on-target toxicities due to neural expression of BCMA. Show less

As the field of modern chimeric antigen receptor (CAR) therapy enters its second decade, clinical trials that demonstrate the efficacy of CAR therapies using randomized clinical trials (RCTs) and/or investigate methods to optimize patient outcomes with commercially available CAR therapies are increasingly important. This systematic review identified 1304 ongoing or upcoming CAR-related trials registered at ClinicalTrials.gov as of December 22, 2020. Of 778 relevant trials, 587 (75%) involved… Show more

As the field of modern chimeric antigen receptor (CAR) therapy enters its second decade, clinical trials that demonstrate the efficacy of CAR therapies using randomized clinical trials (RCTs) and/or investigate methods to optimize patient outcomes with commercially available CAR therapies are increasingly important. This systematic review identified 1304 ongoing or upcoming CAR-related trials registered at ClinicalTrials.gov as of December 22, 2020. Of 778 relevant trials, 587 (75%) involved blood cancers. Twenty-eight studies (4%) sought to optimize outcomes with established CAR therapies using non-CAR drugs or radiotherapy, whereas 3 studies (0.4%) sought to optimize supportive care during CAR therapy. This systematic review found that randomized and optimization-focused trials are comparatively rare within the landscape of ongoing and upcoming CAR-related trials. Show less

CRS remains a significant toxicity of CAR-T therapy for hematologic malignancies. While established guidelines exist for the management of Grade 2+ CRS with immunosuppressive agents such as tocilizumab or corticosteroids, the management of early-grade CRS (i.e. Grade 1 CRS with isolated fevers) has no such consensus beyond supportive care. In this review, we discuss early-grade CRS with an emphasis on its diagnosis, management, and prevention.

Unique toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome limit the ability of chimeric antigen receptor T-cell (CAR-T) therapy to be implemented more widely in the outpatient setting or at smaller-volume centers. In this review, we explore potential niches for digital innovations that can improve the implementation of CAR-T therapy in oncology.

The COVID-19 pandemic has had profound impacts upon scientific discourse in our field, most prominently through the abrupt transition of malignant hematology conferences to all-digital formats. These virtual components will likely be incorporated into future iterations of these conferences even as in-person attendance is reincorporated. In this review, we discuss ways in which usage of the social networking platform Twitter has expanded in the past year during virtual conferences as a method to… Show more

The COVID-19 pandemic has had profound impacts upon scientific discourse in our field, most prominently through the abrupt transition of malignant hematology conferences to all-digital formats. These virtual components will likely be incorporated into future iterations of these conferences even as in-person attendance is reincorporated. In this review, we discuss ways in which usage of the social networking platform Twitter has expanded in the past year during virtual conferences as a method to facilitate — and, in some ways, democratize — information flow and professional networking. Show less

Preemptive administration of tocilizumab (toci) to manage cytokine release syndrome (CRS) after chimeric antigen receptor T-cell (CAR-T) therapy may reduce rates of serious CRS but conversely may worsen neurotoxicity or risk of infections. Our analysis suggests that preemptive toci strategies for CRS management with BCMA-directed CAR-T therapy – specifically, toci administration within 12 hours of the first fever attributed to CRS – do not appear to increase rates of therapy-related toxicities… Show more

Preemptive administration of tocilizumab (toci) to manage cytokine release syndrome (CRS) after chimeric antigen receptor T-cell (CAR-T) therapy may reduce rates of serious CRS but conversely may worsen neurotoxicity or risk of infections. Our analysis suggests that preemptive toci strategies for CRS management with BCMA-directed CAR-T therapy – specifically, toci administration within 12 hours of the first fever attributed to CRS – do not appear to increase rates of therapy-related toxicities or compromise efficacy. However, total CRS duration may be shorter with early-toci workflows. Show less

In a recent multicenter analysis, long geographic distances predicted loss to follow‐up (LTF) among allogeneic hematopoietic cell transplantation (HCT) survivors. We hypothesized that lower frequencies of patient interactions (including in‐person appointments and telemedicine encounters) would predict LTF rather than long driving distances. However, in our retrospective single‐center analysis of 263 HCT survivors, the only predictors of LTF were residence in the furthest driving‐distance… Show more

In a recent multicenter analysis, long geographic distances predicted loss to follow‐up (LTF) among allogeneic hematopoietic cell transplantation (HCT) survivors. We hypothesized that lower frequencies of patient interactions (including in‐person appointments and telemedicine encounters) would predict LTF rather than long driving distances. However, in our retrospective single‐center analysis of 263 HCT survivors, the only predictors of LTF were residence in the furthest driving‐distance quartile and Medicaid insurance (but not annualized frequencies of patient interactions). Our findings suggest that telemedicine may not necessarily "rescue" long‐distance HCT survivors from LTF. Show less

Journeying through a global pandemic with a diagnosis of cancer has undoubtedly been stressful for patients and their caregivers. However, one silver lining of the COVID-19 pandemic - borne out of the desire to keep our patients and clinicians safe - has been a renewed emphasis on maximizing how much time patients can spend at home.

The treatment landscape for relapsed multiple myeloma has expanded considerably in recent years, as numerous agents with new mechanisms of action have been introduced, increasing responses even in advanced disease and prolonging survival. The wealth of novel regimens comes with the challenges of balancing toxicities and aligning a regimen with the biology of the myeloma and the nature of the relapse in conjunction with patient treatment history and personal preference. Herein, we provide an… Show more

The treatment landscape for relapsed multiple myeloma has expanded considerably in recent years, as numerous agents with new mechanisms of action have been introduced, increasing responses even in advanced disease and prolonging survival. The wealth of novel regimens comes with the challenges of balancing toxicities and aligning a regimen with the biology of the myeloma and the nature of the relapse in conjunction with patient treatment history and personal preference. Herein, we provide an overview of treatment options for both early and late relapsing disease as well as a discussion of the role of emerging immune-based therapies. Show less

Multiple myeloma patients undergoing autologous stem cell transplantation (ASCT) may receive benzodiazepine or zolpidem‐class (B/Z) medications despite their risks in older patients. Of 205 myeloma patients (36% aged 65+) who underwent ASCT at our institution between 2017 and 2018, we found that B/Z prescription rates for anxiety/insomnia rose significantly from 26% before ASCT to 38% at discharge and 39% at Day +100. B/Z initiation while hospitalized was a strong predictor of B/Z persistence… Show more

Multiple myeloma patients undergoing autologous stem cell transplantation (ASCT) may receive benzodiazepine or zolpidem‐class (B/Z) medications despite their risks in older patients. Of 205 myeloma patients (36% aged 65+) who underwent ASCT at our institution between 2017 and 2018, we found that B/Z prescription rates for anxiety/insomnia rose significantly from 26% before ASCT to 38% at discharge and 39% at Day +100. B/Z initiation while hospitalized was a strong predictor of B/Z persistence at Day +100. Our findings highlight the role of these potentially inappropriate medications during hospitalizations for ASCT, a period where nonpharmacologic strategies for managing anxiety/insomnia may be feasible. Show less

Post-exposure prophylaxis (PEP) for human immunodeficiency virus (HIV) is recommended to start within hours of needlestick injuries (NSIs) among healthcare workers (HCWs). Using a ‘stat’ workflow to prioritize source patient testing after NSIs, we achieved a modest decrease in order-result intervals and a dramatic decrease in HIV PEP dispensing rates. This simple intervention may improve HCWs’ physical and psychological health during a traumatic time.

Randomized controlled trials designed to test cancer therapies often fail to clarify effectiveness in real-world settings. Herein, we explore lessons for trial development in oncology that can be learnt from the large-cohort, pragmatic RECOVERY trial involving patients hospitalized with COVID-19.

One casualty of the COVID-19 pandemic was in-person professional conferences. However, what may have felt catastrophic has revealed unique opportunities to engage individuals in professional offerings, including those who, because of cost or travel, may not have previously participated. In this article, the authors present insights into how to optimize virtual learning experiences during the COVID-19 pandemic and beyond.

Long driving distances to transplantation centers may impede access to care for hematopoietic cell transplantation (HCT) survivors. However, in our multicenter analysis, we found no impact of driving distance on psychosocial distress and physical function among HCT survivors. In contrast, predictors of both elevated distress and impaired physical function included a lack of Internet access. Our results have implications for how long-term follow-up care is delivered after HCT, both with regard… Show more

Long driving distances to transplantation centers may impede access to care for hematopoietic cell transplantation (HCT) survivors. However, in our multicenter analysis, we found no impact of driving distance on psychosocial distress and physical function among HCT survivors. In contrast, predictors of both elevated distress and impaired physical function included a lack of Internet access. Our results have implications for how long-term follow-up care is delivered after HCT, both with regard to the negligible impact of driving distances on patient wellness and also the risk of a 'digital divide' worsening outcomes among HCT survivors. Show less

Retrospective analyses of observational registries are used to justify a wider range of treatments, including the delivery of radiotherapy and surgery. However, a key question remains: when a physician relies on an observational study to make a therapeutic recommendation, how often is that recommendation correct?

Profanities and promises start similarly as words, but they end quite differently. Profanities exist to express the emotions of their sender, while promises exist to elicit emotions from their receiver. At Ms. D’s bedside, though, the two always felt strikingly similar: she loved using both of them as much as we hated them.

Once upon a time, discharges were easy to categorize: good, bad, or ugly. Good discharges allowed the patient to leave before noon, while bad discharges allowed the patient to leave without follow-up appointments. The worst discharges were defined by the two ugly cousins of acute care re-escalation: return ED visits and readmissions. Recently, however, much of this conventional wisdom has been turned on its head.

We appreciated Inamoto and Lee’s thoughtful review summarizing the late effects of hematopoietic stem cell transplantation (HCT), particularly their dual emphasis on both the prevention and treatment of potential complications. In the interest of broadening the scope of their review, we wish to draw attention to two additional and frequently overlooked complications of HCT: female sexuality and financial toxicity.

Postdischarge follow-up visits (PDFVs) are widely recommended to improve inpatient-outpatient transitions of care. In our health system, PDFVs were scheduled for more than half of hospitalizations but 25% resulted in no-shows or same-day cancellations. New strategies are needed to improve PDFV attendance.

In the medical intensive care unit (MICU), death is simultaneously everywhere and nowhere. When patients die, they disappear from our census, and their rooms are quickly repopulated by other critically ill patients. MICU patients who die are ostensibly forgotten - not today, though. Today is Grieving Rounds.

Health literacy means understanding one’s health, but substitute health with patient… Now I myself have patient illiteracy, for which patience is the only treatment.

Ibrutinib dose reduction may not affect clinical outcomes. Weight-based dosing and pharmacoeconomic analyses should be considered in future studies of ibrutinib.

Thinking back to Mr. H's case... a laryngectomy is as life-altering as it is life-saving, and paper provides a poor substitute for the inflection inherent to the human voice.

Patients treated for a hematologic malignancy are at risk for treatment-related complications. The risk for each complication is dictated by patient characteristics including age, co-morbidities, and genetic predispositions, as well as the specifics of therapy.

Despite increasing awareness, fertility is not universally discussed with premenopausal breast cancer patients at the time of diagnosis. Even when such discussions are documented, only about half of patients recall the conversation. Patient-reported barriers to fertility preservation include lack of education, financial costs, and perceived treatment toxicities.

In a multicenter survey of 557 medical students, almost one third of students expressed an interest in careers related to clinical informatics (CI). Students, even those with career interest in CI, were generally unaware of CI training and mentoring opportunities available to them.

Ms. G was a 64-year-old homeless female, a longtime smoker, who had been diagnosed with metastatic lung cancer after presenting to the hospital for new-onset voice hoarseness. I was a 24-year-old student, newly starting my third year of medical school, who had been assigned to Ms. G after presenting to the same hospital for my first clerkship.

Progressive Multifocal Leukoencephalopathy (PML) is a fatal disease with limited treatment options caused by the JC polyomavirus (JCPyV). We show that the human defensin HD5 blocks JCPyV by blocking viral uncoating in the Endoplasmic Reticulum and by stabilizing the viral capsid.

A 44-year-old male with no past psychiatric or neurological history was admitted after multiple suicide attempts in 6 months. After minimal response to standard therapy, a medical workup resulted in the surprising diagnosis of neuroborreliosis. The patient recovered entirely (both by subjective and objective measures) after treatment with intravenous antibiotics.

Polyomaviruses such as the BK virus are a family of viruses that are able to transform cells and promote tumor formation. In this study, we used immunofluorescent techniques, FACS analysis, and luciferase assays to determine that the BK virus can efficiently infect the pulmonary carcinoid H727 cell line.