Safety and Efficacy of BCMA directed Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Plasma Cell Leukemia.

Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL treated with the B-cell Maturation Antigen (BCMA)-directed Chimeric Antigen Receptor T-Cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients, 19 patients received ide-cel and 15 received cilta-cel.

Immune-MRD status informs tumor-MRD outcome prognostication in patients with multiple myeloma on lenalidomide maintenance.

Purpose: Lenalidomide maintenance is the most frequently utilized approach for newly diagnosed multiple myeloma (MM) patients following induction therapy with/without consolidative high-dose melphalan and autologous stem cell transplantation. Baseline and longitudinal measurable residual disease (MRD) negative status is a well-established positive predictive sign in lenalidomide maintenance patients. However, the clinical utility of serial MRD assessments remains uncertain, as there is no consensus on the clinical management of MRD-resurgence (MRDres) or stable remissions in patients positive for MRD.

New Comorbidity Index Associated with Survival After Chimeric Antigen Receptor T Cell Therapy for Large B-Cell Lymphoma.

The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T cell (CAR-T) therapy is not well-established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017-2020 were selected from the CIBMTR registry.

Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: A CIBMTR Analysis.

Relapsed and/or refractory Richter transformation (RT) is generally associated with poor response to available therapies and a short survival time. As RT patients were excluded from participating in the pivotal studies of chimeric antigen receptor T cell therapy (CAR-T) for large B-cell lymphoma, there is a paucity of information about the efficacy of CAR-T in RT. Therefore, through the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed data from 140 RT patients who received anti-CD19 CAR-T between 2018 and 2023.

Real-World Outcomes of Sequential BCMA-directed therapies in Relapsed Refractory Multiple Myeloma After Belantamab Exposure.

Background: While B-cell maturation antigen (BCMA) directed therapies are increasingly utilized for multiple myeloma, outcomes with sequential treatments with BCMA-directed therapies remain an area of active investigation.

Methods: In this multicenter retrospective analysis, we evaluated the real-world outcomes of patients treated with BCMA-directed therapies including CAR T and bispecific antibody (BsAb) following progression on the antibody-drug conjugate belantamab mafodotin. A total of 23 patients (14 CAR T, 9 BsAb) were included in the analysis.

Outcomes in frail patients receiving BCMA-directed bispecific antibodies for relapsed/refractory multiple myeloma.

Patients with relapsed/refractory (R/R) multiple myeloma (MM) are often frail with preexisting comorbidities and poor performance status (PS). To evaluate clinical characteristics and outcomes based on frailty, we conducted a single-center retrospective study of patients with R/R MM who received B-cell maturation antigen (BCMA)-directed bispecific antibodies (BsAbs). Frailty was defined using the simplified frailty index based on age, Eastern Cooperative Oncology Group (ECOG) PS, and Charlson comorbidity index (CCI; nonfrail score 0-1 and frail score ≥2).

Cytokine Release Syndrome and Neurotoxicity Following CD19 CAR-T in B-Cell Lymphoma.

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns. Analyze temporal trends, risk factors, and associations between these toxicities and their severity.

T-ICAHT: grading and prognostic impact of thrombocytopenia after CAR T-cell therapy.

Immune effector cell-associated hematotoxicity (ICAHT) was recently introduced as a distinct toxicity category of chimeric antigen receptor (CAR) T-cell (CAR-T) therapy. Although a grading system based solely on neutrophil counts was proposed (hereafter termed N-ICAHT), the prevalence and prognostic impact of thrombocytopenia remain poorly defined. In this multicenter observational study, we systematically examined patterns of thrombocytopenia in 744 patients treated with commercial CD19 CAR-T for B-cell non-Hodgkin lymphoma (B-NHL).

Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel) was the first US Food and Drug Administration-approved chimeric antigen receptor T-cell (CAR-T) therapy for multiple myeloma (MM). However, because clinical trials are highly selective with stringent eligibility criteria, the objective of this study was to evaluate the safety and effectiveness of standard-of-care (SOC) ide-cel in the real world. Using the Center for International Blood and Marrow Transplant Research registry, we evaluated 821 patients who received SOC ide-cel.

A real-world experience of efficacy and safety of belantamab mafodotin in relapsed refractory multiple myeloma.

While initial trials led to the accelerated approval of belantamab mafodotin, a BCMA-directed antibody-drug conjugate, confirmatory trials failed to establish benefit from this therapy for patients with relapsed refractory multiple myeloma (RRMM), eventually leading to its withdrawal from commercial use. With an imminent approval as an effective combination therapy, as seen in recent randomized trials, we report real-world clinical outcomes with belantamab mafodotin in 81 RRMM patients. With a median of 5 (range 2-15) prior lines of therapy, 92, 45, and 15% of the patients were triple-class refractory, penta-class refractory, and BCMA-refractory.

Comparison of Standard-of-Care Idecabtagene Vicleucel and Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma.

Purpose: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), two B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). We compare safety, efficacy, and survival among patients with RRMM treated with standard-of-care (SOC) ide-cel or cilta-cel.

Methods: Data were from a retrospective chart review of patients with RRMM leukapheresed by December 31, 2022, with the intent to receive SOC ide-cel or cilta-cel at 19 institutions.

Addition of Elotuzumab to Backbone Treatment Regimens for Multiple Myeloma: An Updated Meta-Analysis of Randomized Clinical Trials.

Background: The efficacy of elotuzumab, an anti-SLAMF7 monoclonal antibody, in treating relapsed/refractory multiple myeloma (RRMM) and newly-diagnosed multiple myeloma (NDMM) has varied in randomized controlled trials (RCTs). Moreover, there is limited data on its real-world application.

Patients And Methods: We conducted a systematic review and meta-analysis of RCTs investigating the addition of elotuzumab to backbone antimyeloma regimens.

: A condensed step-up dosing schedule of teclistamab for relapsed/refractory multiple myeloma.

Teclistamab is a B-cell maturation antigen (BCMA)-directed bispecific T-cell engager approved for relapsed-refractory multiple myeloma (RRMM). Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) are well-documented treatment -related adverse events of teclistamab. The prescribing information recommends step-up dosing on days 1, 4, and 7 with 48-72 h of inpatient observation after each dose to monitor for CRS.

Timing of Toxicities and Non-Relapse Mortality Following CAR T Therapy in Myeloma.

BCMA-directed chimeric antigen receptor T-cell (CAR T) therapies, including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have transformed the treatment landscape for relapsed-refractory multiple myeloma (RRMM), offering remarkable efficacy with hallmark toxicity risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The FDA mandates a 4-week monitoring period at the treatment center as part of a Risk Evaluation and Mitigation Strategy (REMS) to monitor and manage these toxicities, which, while prudent, may add unnecessary challenges related to access and socioeconomic disparities. We sought to assess CRS and ICANS onset and duration, as well as causes of non-relapse mortality (NRM) in real-world BCMA CAR T recipients in order to better inform future changes to the monitoring guidelines for CAR T recipients.

Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel.

Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions.

Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma Immunotherapy Consortium Real- World Experience.

Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.

Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy.

The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T.

Beyond BCMA: the next wave of CAR T cell therapy in multiple myeloma.

Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment landscape of relapsed/refractory multiple myeloma. The current Food and Drug Administration approved CAR T cell therapies idecabtagene vicleucel and ciltacabtagene autoleucel both target B cell maturation antigen (BCMA), which is expressed on the surface of malignant plasma cells. Despite deep initial responses in most patients, relapse after anti-BCMA CAR T cell therapy is common.

TACTUM: Trends in Access to Cellular Therapies in Multiple Myeloma, Perspectives of Treating Versus Referring Physicians.

Chimeric antigen receptor T cell therapy (CAR-T) and bispecific T cell engagers (TCE) for multiple myeloma (MM) are readily available at many large US medical centers. However, many potentially eligible patients may not be referred to the specialized centers administering these therapies. Perspectives regarding potential barriers for MM cellular therapy from referring-center oncologists (ROs) versus treating-center oncologists (TOs) have not been reported previously.