Real-World Treatment Patterns and Outcomes of Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (BiTE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM) at the Yale Cancer Center Network (YCCN)

Introduction:

The advances in T-cell redirection therapies (TRT) are changing the treatment paradigm in RRMM with unprecedented response rate and progression free survival (PFS) observed in clinical trials. Data on treatment patterns, efficacy and safety of TRT in the real-world setting are still limited. This study examined the real-world treatment patterns and compared clinical outcomes of CART and BiTE therapies in patients (pts) with RRMM at the YCCN.

Methods:

We conducted a retrospective observational study of all pts, age ≥18, with MM who were treated with commercial CART or BiTE within the YCCN between October 2021 and April 2024. Pts’ demographics and clinical characteristics were manually reviewed. Response was assessed by the International Myeloma Working Group criteria. Response to treatment was defined as ≥partial response. Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) were graded using the American Society for Transplantation & Cellular Therapy system. Severe cytopenias were defined as ≥grade 3 for ≥1 month (mo) and severe infections were defined as those resulting in sepsis. Timely treatment was defined as TRT at ≤5 line of therapy (LOT). Student t tests for continuous variables and χ² tests for categorical variables were used to compare difference between groups. We used multivariable logistic regression model to identify factors that impact timely treatment. Multivariable Cox proportional hazard models were used to assess factors associated with overall survival (OS) and PFS.

Results:

We identified 92 pts with a median age of 66.4 years (y) (interquartile range [IQR] 59-71.3). Most pts were male (60.9%), non-Hispanic white (70.7%), IgG isotype (53.3%), R-ISS stage 2-3 (47.8%), had commercial insurance (57.6%), high-risk cytogenetics (57.6%) and ECOG 0-1 (73.9%). 43.5% had extramedullary disease (EMD). Non-Hispanic black pts had reasonable access to TRT within the YCCN (14.1% of all pts).

46 pts received CART (39 idecabtagene vicleucel, 7 ciltacabtagene autoleucel) and 46 received BiTE (36 teclistamab-cqyv, 10 talquetamab-tgvs). CART was given to pts with younger age compared to BiTE (mean age at CART was 62.9 y vs BiTE was 67.9 y, p<0.01).

73.9% received CART and 78.3% received BiTE at ≥LOT6. Median prior LOT was 6 (range 3-16). Cyclophosphamide+etoposide+dexamethasone (+/-cisplatin) was the most common CART bridging regimen. 65.2% had transplant prior to TRT. After a year of 1^st FDA approval of each TRT, 35.9% of CART pts and 42.1% of BiTE pts received TRT at ≥LOT8. The multivariable logistic regression model showed older age (≥65 y) was more likely to receive timely TRT (odds ratio 4.38, 95% confidence interval CI 1.16-16.49, p=0.03).

After a median follow-up of 10.8 mos (IQR 6.2-16.2), 89.1% CART (87.2% idecabtagene, 100% ciltacabtagene) and 63% BiTE (58.3% teclistamab, 80% talquetamab) pts responded (p<0.01). 80.4% CART and 60.9% BiTE pts had ≥very good partial response. Median response duration was 9.4 mos (IQR 4.9-13.6) in CART and 7 mos (IQR 5.1-9.2) in BiTE.

52.2% of CART and 52.2% of BiTE progressed with median time to progression of 5.8 mos (IQR 2.8-9.4) in CART and 0.9 mos (IQR 0.5-5.3) in BiTE (p=0.02). 82.6% in CART and 50% in BiTE had CRS (0% grade ≥3 in CART and 4.3% in BiTE, p<0.01). 37% in CART and 13% in BiTE had ICANS (29.4% grade ≥3 in CART and 0% in BiTE, p=0.01). More CART pts (67.4%) had severe cytopenias than BiTE pts (32.6%, p<0.01). Only 2.2% in CART and 6.5% in BiTE had severe infections.

23.9% of CART pts and 26.1% of BiTE pts died (none attributed to TRT adverse events (AE)). Median PFS in CART was 12.9 mos (95% CI, 6.4-NE) and in BiTE was 6.7 mos (95% CI, 2.1-13.1). EMD was associated with PFS with adjusted hazard ratio (HR) 2.03 (95% CI, 1.09-3.79), p=0.03. OS did not reach median though ECOG 2-4 was associated with OS with adjusted HR 3.53 (95% CI, 1.35-9.22), p=0.01.

Conclusion:

This analysis highlighted that when compared to BiTE, CART showed statistically significant deeper response and better response duration, but higher CRS, neurotoxicity and severe cytopenia incidence. Severe infection incidence was low in both groups. None of the deaths were due to TRT AE. CART was given to pts with younger age compared to BiTE. Over 70% of pts still received TRT at ≥LOT6. One study limitation is a small sample size from a single institutional experience. Another real-world study using a larger cohort across oncology care settings is underway.