Chimeric antigen receptor (CAR) T cell therapy is changing the paradigm in hematologic malignancies, but disparities in access exist in the real-world setting. Efforts to address and eliminate these disparities will ensure availability of this life-saving therapy. This study aimed to determine patterns of racial/ethnic distribution, socioeconomic strata, insurance coverage, and travel time of CAR T cell recipients. We used the Vizient Clinical Database (CDB) to capture and analyze elective encounters for CAR T administration as well as encounters for any reason other than CAR T administration (non-CAR T) in patients with lymphoma, myeloma, and acute lymphoblastic leukemia. Travel time and median household income were calculated based on ZIP code of residence. We found that African Americans (AA) were less likely than other racial/ethnic groups to receive CAR T cell therapy. In addition, AA and Hispanic participants were underrepresented in clinical trials. Among the patients with myeloma, all of whom received CAR T cell therapy on a clinical trial, only 1% were African American and 5.4% were Hispanic, and only 7.3% of CAR T cell therapy-related admissions were of patients from neighborhoods with a mean income <$40,000. Almost one-third of the CAR T cell recipients lived >2 hours away from the center in which they were treated; the majority of these patients were from the higher socioeconomic stratum (P < .001). There were fewer patients with Medicare and uninsured patients in the CAR T cell group. Our data indicate that socioeconomic stratum and insurance coverage are important underlying determinants of the identified disparities. Low clinical trial enrollment of minorities also feeds the inequity. Strategies to improve access need to be framed around addressing the causes for the observed disparities.

Teclistamab is a B-cell maturation antigen (BCMA)-directed bispecific antibody approved for relapsed-refractory multiple myeloma (RRMM) on the basis of the phase I/II MajesTEC-1 trial. Herein, we report clinical outcomes with standard-of-care teclistamab in a real-world RRMM population. A total of 106 patients from five academic centers who received teclistamab from 8/2022 to 8/2023 were included in this retrospective analysis; 83% of whom would have been considered ineligible for the MajesTec-1 trial. All patients were triple-class exposed, 64% were penta-class refractory, and 53% had received prior BCMA-directed therapy. Cytokine release syndrome was observed in 64% of patients and only one event was grade ≥3, while immune effector cell-associated neurotoxicity syndrome was observed in 14% of patients (three events were grade 3-4). One-third (31%) of patients experienced at least one infection, with nearly half of these infections graded as severe (grade ≥3). The overall response rate (ORR) and complete or better response rate were 66% and 29%, respectively. The ORR was 47%, 59% and 68% for patients with extramedullary disease (EMD), prior BCMA-directed therapy, and penta-refractory disease, respectively. At a median follow-up of 3.8 months, the median progression-free survival (PFS) was 5.4 months (95% CI, 3.4 months-not reached), while median overall survival was not reached. Patients with Eastern Cooperative Oncology Group performance status ≥2, EMD, and age ≤70 years had inferior PFS on multivariable analysis. Our study demonstrates reasonable safety and good efficacy of teclistamab in patients with RRMM treated in the real-world setting.

Chimeric antigen receptor T cell (CAR T) therapy has been integrated into treatment algorithms for acute leukemia, lymphoma, and, most recently, multiple myeloma. The number of clinical trials in both hematologic and solid tumor malignancies for new products and potential indications continues to grow. The clinical toxicities of CAR T therapy include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which often warrant inpatient admission for close monitoring and treatment. Consequently, many centers have built processes around the administration of these cells in the inpatient setting. As new products gain Food and Drug Administration approval with more manageable toxicity profiles, and as institutions gain experience with the management of these toxicities, outpatient administration and monitoring should be expected. In addition, payor reimbursements for inpatient treatment have put the sustainability of inpatient CAR T therapy in jeopardy, especially for centers with a payor mix that includes a high proportion of Medicare patients. This has the serious potential to limit access to care. As the use of CAR T therapy continues to expand, changes in payment models, care settings, or both are needed to ensure the sustainability of safe, efficient, and cost-effective treatment. This review outlines the efficacy and toxicity of currently approved products, as well as best practices to optimize the management of CAR T cell therapy in the outpatient setting.

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. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p < 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p < 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p < 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion.

Despite the astonishing outcomes after chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory multiple myeloma (RRMM), most patients eventually relapse. There are only limited data available on salvage therapies following relapse after BCMA-directed CAR T-cell therapy. Here, we analyzed outcomes of post-CAR T-cell therapy relapse and impact of different salvage strategies in an international cohort of 139 patients (n = 130 ide-cel, n = 9 cilta-cel), receiving talquetamab (n = 28), teclistamab (n = 37), combinations of immunomodulating drugs (IMiDs), proteasome inhibitors (PIs) or CD38 monoclonal antibodies (n = 43), and others (n = 31). The median time to relapse after CAR T-cell therapy was 5 months, 53% had the extramedullary disease (EMD) at relapse, associated with dismal post-relapse outcome (P = 0.005). Overall response and complete response upon salvage therapies were 79% and 39% for talquetamab, 64% and 32% for teclistamab, 30% and 0% for IMiDs/PIs/CD38, and 26% and 3% for others (P < 0.001). Duration of response, as well as median survival, was significantly improved with bispecific antibodies (P < 0.001, respectively). Bispecific antibodies seemed to overcome the poor prognosis associated with early relapse and EMD, and were independent predictors for improved survival in multivariable analysis. In summary, these results suggest bispecific antibodies as the standard of care for relapse after CAR T-cell therapy for RRMM.