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•We explored the impact of ALC on the survival outcomes of myeloma patients treated with commercial idecabtagene vicleucel.•We created a new ALC profile and included 3 groups: Normal pre-lymphodepletion (LD) ALC, low pre-LD ALC + percent reduction (%R) from pre-apheresis to pre-LD of <37.5 and low pre-LD ALC + %R ≥37.5.•Low pre-LD ALC with high %R from pre-apheresis to pre-LD was associated with inferior survival outcomes.

⁃The novel EHA/EBMT grading of ICAHT closely reflects the extent of hematological toxicity following BCMA and CD19-directed CAR-T therapy.⁃Severe ICAHT was associated with transfusion use, an increased rate of severe infections and adverse treatment outcomes with high NRM.

Introduction

Background:CD19-directed chimeric antigen receptor T-cell (CAR T) therapy with axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel) are FDA-approved for relapsed and/or refractory (r/r) large B-cell lymphoma (LBCL) after ≥2 prior lines of systemic therapy (all 3) or earlier after 1 line (axi-cel and liso-cel) based on durable remissions of 30-40%. Pivotal trials and real-world data demonstrated notable heterogeneity in toxicity and efficacy between CAR T products. To account for such differences, we have established a novel composite endpoint of toxicity-free, progression-free survival within 6 months (TPFS6) after CAR T-cell therapy. We also studied factors associated with TPFS6 across CAR T-cell products and its impact on long-term success of CAR T-cell therapy.

Introduction: Idecabtagene vicleucel (ide-cel) was the first FDA approved BCMA targeted CAR-T cell therapy for the treatment of relapsed/refractory multiple myeloma (RRMM). However, clinical trials are highly selective with stringent eligibility criteria. The objective of this study was to evaluate the safety and efficacy of standard of care ide-cel.

Introduction.Idecabtagene vicleucel (ide-cel) is a chimeric antigen receptor T-cell therapy (CAR-T) approved for patients with triple-class exposed relapsed/refractory multiple myeloma (TCE RRMM) (Munshi NC, et al. N Engl J Med2021;384:705-716). Treatment-related toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are prevalent and common to all CAR T-cell therapies. We examined the association of serum cytokines and pre-CAR-T bone marrow composition with toxicity and early response among patients with TCE RRMM treated with ide-cel.

Introduction:Daratumumab, lenalidomide, and dexamethasone (DRd) and bortezomib, lenalidomide, and dexamethasone (VRd) are the only two regimens that are considered as preferred per the National Comprehensive Care Network for transplant ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). While there are no head-to-head studies comparing clinical outcomes of DRd and VRd in this population, an indirect comparison (PEGASUS study [Durie et al., 2020]) has shown that DRd was associated with significantly lower risk of disease progression or death compared with VRd and Rd. This study aims at supplementing this information by comparing real-world time-to-next-treatment (TTNT) or death between NDMM TIE patients treated with front-line (FL) DRd or VRd.

Introduction:The rapid evolution of novel chimeric antigen receptor T-cell (CAR-T) therapies, including Carvykti (ciltacabtagene autoleucel) and Abecma (idecabtagene vicleucel), have revolutionized the treatment landscape for multiple myeloma (MM) patients. These cutting-edge therapies have demonstrated remarkable efficacy in clinical trials, representing a significant advancement in the field. However, their real-world impact on patient and physician experiences, and perceptions remain important topics of ongoing investigation. In recent years, social media platforms have emerged as valuable sources of real-time data and patient perspectives, providing an unprecedented opportunity for researchers to gain insights into physician and patient perceptions around these emerging CAR-T therapies. This study aims to perform a comprehensive digital analysis to measure sentiment expression by different health care stakeholders and to identify health information needs related to MM CAR-T therapies.

Background:The use of CAR-T cell therapy has transformed treatment paradigms in B-cell malignancies. Ciltacabtagene autoleucel (cilta-cel) was approved for use in RRMM after four or more prior lines of therapy in 2022. While the pivotal studies exclusively treated patients in an inpatient setting, robust infrastructure planning at some centers across US has fostered outpatient administration of the commercially available product. Outpatient administration of CAR-T is more desirable due to superior financial sustainability, lower healthcare resource utilization, and greater patient autonomy during the treatment. Hence, we conducted a qualitative study to evaluate clinical and administrative perspectives and trends in outpatient administration of commercialized cilta-cel with an aim to understand best practices from certified CAR-T centers in the USA.

Background:Hematological toxicity is a frequent side effect of CAR-T therapy and predisposes for severe infectious complications. Recently, the EHA/EBMT consensus grading for Immune Effector Cell Associated HematoToxicity (ICAHT) was developed ( Rejeski et al. Blood 2023). In contrast to existing grading systems such as the CTCAE, the novel ICAHT grading integrates both the depth and duration of neutropenia. We hypothesized that ICAHT severity is associated with key clinical sequelae such as transfusion requirements, hospitalization, severe infections, and adverse treatment outcomes.

Introduction

Introduction:Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor-T cell (CAR-T) immunotherapy approved for patients with relapsed or refractory multiple myeloma (RRMM). In the phase 3 trial, CARTITUDE-4 (NCT04181827), cilta-cel demonstrated better efficacy than physician's choice (daratumumab plus pomalidomide and dexamethasone [DPd] or pomalidomide plus bortezomib and dexamethasone [PVd]) with an overall response rate (ORR) of 84.6% versus 67.3% and ≥complete response (CR) of 73.1% versus 21.8% (San-Miguel et al. New Engl J Med. 2023). The present analysis assessed the value of cilta-cel and physician's choice treatments within the CARTITUDE-4 trial from a US combined commercial and Medicare payer perspective using a novel cost per responder (CPR) model that incorporates efficacy and total treatment costs.

Introduction:Ide-cel is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy associated with deep and durable responses and improved quality of life among triple-class exposed (TCE) patients with relapsed/refractory multiple myeloma (RRMM) (Munshi NC, et al. N Engl J Med2021;384:705-716; Delforge M, et al. Blood Adv2022;6:1309-1318). An analysis of 2-year post-infusion facility-related HCRU (fHCRU) associated with ide-cel treatment in the phase 2 KarMMa clinical trial (NCT03361748) found that most facility costs were incurred within the first month following infusion where the median hospital length of stay (LOS) was 19.5 days which included the clinical trial requirement of hospitalization for monitoring and 20% of the patients had intensive care unit (ICU) stays (McGarvey N, et al. Blood2022;140(suppl 1):10947-10948). In this study, we estimated fHCRU and associated costs for patients with TCE RRMM receiving ide-cel in RW clinical practice.

Introduction

Introduction: Multiple myeloma (MM), remains an incurable, but treatable, malignancy that has benefitted from the integration of novel immunologic agents in clinical use, such as monoclonal antibody, bispecific T cell engager (TCE) and chimeric antigen receptor T (CAR-T) cell and antibody-drug conjugate based therapies. While these agents have shown great promise in treating relapsed/refractory MM patients, there is heterogeneity in response to therapy due to differences in patients' immune tumor microenvironments (iTME) and immunogenicity of the tumor cells. Previously (Sudalagunta et. al., ASH 2021), we used functional genomic screening of 53 MM samples to characterize the transcriptomic profile associated with sensitivity to the selective nuclear export inhibitor, selinexor (SELI), which was shown to be inversely correlated with the transcriptomic profile associated with sensitivity to an anti-CD38 monoclonal antibody in 106 MM samples. In this study, we investigate the cellular mechanisms of SELI resistance leading to an immunogenic cell state.

Introduction:BCMA-directed chimeric antigen receptor T-cell therapy (CAR T), idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), are approved for patients with relapsed and/or refractory (R/R) multiple myeloma (MM). Pivotal KaRMMA and CARTITUDE-1 trials as well as real-world data demonstrated heterogeneity in toxicity and efficacy between ide-cel and cilta-cel. To account for such differences, we have established a novel composite endpoint of toxicity-free, progression-free survival within 3 months (TPFS3) after anti-BCMA CAR T therapy. We also studied factors associated with TPFS3 across ide-cel and cilta-cel and the impact of TPFS3 on overall survival (OS) after CAR T.

Introduction:Lymphodepletion (LD) chemotherapy is critical for the efficacy of CAR-T therapy by eradicating immunosuppressive cells, inducing costimulatory molecules, and promoting expansion and persistence of CAR-T cells. It also can contribute to an increased risk of infections, cytopenia, and other toxicities. We evaluated the utilization of varying LD regimens used in standard-of-care (SOC) autologous B-cell maturation antigen-directed (BCMA) CAR-T therapy with ide-cel or cilta-cel for relapsed/refractory multiple myeloma (RRMM) and the effect on outcomes and toxicity.

Introduction: Teclistamab (TEC) received regulatory approval for the treatment of patients with Relapsed/Refractory Multiple Myeloma (RRMM) after ≥ 3 prior lines of therapy based on the results of the pivotal MajesTEC-1 trial in which such patients achieved an overall response rate (ORR) of 63%, ≥ complete response (CR) of 39%, and median progression free survival (PFS) of 11.3 months (Moreau et al. N Engl J Med2022). Patients who had received a prior B-cell maturation antigen-targeted therapy (BCMA-TT) were excluded from MajesTEC-1 trial. Data on the efficacy of TEC in patients who have received and relapsed after prior BCMA targeted therapy is lacking. Several studies have shown reduced efficacy of both FDA approved BCMA targeted chimeric antigen receptor T cell therapies (CAR-T) for myeloma, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), when administered after BCMA targeted bi-specific antibodies. There is a paucity of data on the efficacy of TEC when administered in patients who progress after ide-cel or cilta-cel. We evaluated the real-world outcomes of patients treated with standard of care (SOC) TEC after having previously received a BCMA-TT.

The article titled "The 2023 Ladies' Tour" describes a trip taken by a group of women to Port Clinton, Ohio. The women participated in a candle-making party at the Island Sham Farmhouse and learned about choosing fragrance oils, pouring wax, and avoiding bubbles. Afterward, they enjoyed an Italian lunch and visited the Schedel Arboretum and Gardens in Elmore, which features the world's largest collection of lithophanes and a Bonsai Shelter with a renowned collection of sculptures. The women had a unique and enjoyable learning experience during their tour. [Extracted from the article]

We present the first reported case of Sporopachydermia cereanain the United States. The patient, a 58-year-old neutropenic woman with acute myelogenous leukemia, had blood cultures initially identified as Candidaspecie, but then identified as S. cereana. She responded to antifungal therapy concurrent with recovery of her counts.

•Increased infections and delayed CD4+T cell recovery are seen with post-transplantation cyclophosphamide (PTCy).•B cell recovery is faster with PTCy compared with conventional graft-versus host disease (GVHD) prophylaxis.•The incidence of cytomegalovirus infection is 2 to 3 times higher with PTCy.•The incidence of bacterial and viral infections, but not of fungal infection, is higher with PTCy.•Nonrelapse mortality and overall survival are similar with PTCy and conventional GVHD prophylaxis.

The article report that a group of 12 ladies toured the Milwaukee Art Museum located at the shore of Lake Michigan where they marveled at the architecture of the Santiago Calatrava-designed Quadracci Pavilion on September 4, 2015.