Jagannath, Sundar

Abstract Chimeric antigen receptor (CAR) T-cell therapy enriched for a memory-like phenotype may persist and function longer than a nonenriched product, thereby improving duration of response (DOR). We conducted a phase I study with bb21217 (NCT03274219), an anti–B-cell maturation antigen CAR T-cell therapy manufactured in the presence of the phosphoinositide 3-kinase inhibitor bb007 to enrich for T cells with a memory-like phenotype, in patients with relapsed/refractory multiple myeloma (N = 72). No new safety concerns were raised with bb21217 therapy (three cases each of grade ≥3 cytokine release syndrome and grade ≥3 neurotoxicity were observed). The objective response rate was 69.4% and the median DOR was 23.8 (95% confidence interval, 16.8–34.8) months. Analysis of the drug product established an association between early memory phenotype and robust expansion and depth of response. Examination of baseline characteristics indicated that tumor burden and prior therapies influenced DOR. The data indicate that generation of CAR T cells early in a disease course when tumor burden is lower and source material exhibits a more naïve phenotype may maximize the clinical benefit potential of the drug product.

8027 Background: The Connect MM Registry is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed multiple myeloma (NDMM) and one of the largest, longest running MM registries. Long-term survivors (LTS), defined as patients (pts) who have ≥ 8 years of follow-up, comprise a large portion of the Connect MM Registry. The purpose of this analysis was to assess LTS demographic and clinical characteristics. Methods: Adult pts with NDMM (N = 3011) were enrolled from 250 community, academic, and government sites: Cohort 1 from 2009 – 2011 and Cohort 2 from 2012 – 2016. As 99% of LTS were enrolled in Cohort 1, only pts from Cohort 1 were included in this analysis. Pt data were unevaluable if there were missing treatments, disease assessments, or large gaps in activity during follow-up (n = 28). Baseline characteristics, treatment patterns, and quality of life (QoL) form completion rates were examined. Results: At data cutoff (5/17/21), of the 1493 pts in Cohort 1 with evaluable data, 279 were LTS and 1186 were non-LTS. LTS were generally younger and had better performance status at enrollment (Table). Most (66%) LTS received stem cell transplants and few experienced progression within the first 6 months (3%). Top first-line (1L) regimen for LTS was lenalidomide/bortezomib/dexamethasone (31%) vs bortezomib/dexamethasone (22%) in non-LTS. At data cutoff, 73% of LTS were still on treatment at their most recent visit. LTS underwent disease assessments more frequently (2.0 vs 1.3 per year) and had a higher QoL completion rate by year 5 (58% vs 46%). This analysis showed an estimated 8-year survival of 36% vs an observed 8-year survival of 39% from the SEER database. Additional analyses are ongoing. Conclusions: LTS were younger and healthier than non-LTS. Most LTS received triplets at induction, stem cell transplants in 1L, and were less likely to relapse within the first 6 months of treatment than non-LTS. These findings are consistent with what has been observed in MM clinical trials. Further, this analysis demonstrates the value of longitudinal data in the CONNECT MM Registry and provides insights on long surviving pts with MM. Clinical trial information: NCT01081028. [Table: see text]