Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience

Abstract

While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤3 months after CAR T-cell infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤3 months of infusion (P<0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (P<0.001; median PFS for ≥3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T-cell therapy who may benefit from specific interventions pre and post CAR T-cell therpy to improve outcomes.

Figure 1.

Consort diagram of study inclusion. Ide-cel: idecabtagene vicleucel.

Figure 2.

Best response by early progression. Any patient who was not evaluable by International Myeloma Working Group criteria or was missing a response but reached day 30 was considered as a partial response (PD) response. CR: complete response; sCR: stringent complete response; VGPR: very good partial response; MRD: minimal residual disease.

Figure 3.

Survival analysis by early progression. (A) Kaplan-Meier survival curve of progression-free survival (PFS) by early progression. (B) Kaplan-Meier survival curve of overall survival (OS) by early progression. The P value is from a log-rank test of the association of early progression with PFS and OS. CI: confidence interval, NR: not reached.

Figure 4.

Survival analysis by number of early progression risk factors. (A) Kaplan-Meier survival curve of progression-free survival (PFS) by number of early progression risk factors. (B) Kaplan-Meier survival curve of overall survival (OS) by number of early progression risk factors. Early progression risk factors included prior B-cell maturation antigen therapy, extramedullary disease, baseline ferritin, plasma cell leukemia, and t(4;14). The P value is from a log-rank test examining the association of the number of early progression risk factors (0, 1, 2, ≥3 factors) with PFS and OS. CI: confidence interval; NR: not reached.