Prior Exposure to Belantamab Mafodotin Influences Outcomes with Idecabtagene Vicluecel in Patients with Multiple Myeloma

Introduction: B-cell maturation antigen (BCMA) has emerged as a promising target for therapies in patients with relapsed/refractory multiple myeloma (RRMM). Belantamab mafodotin is an antibody-drug conjugate (ADC) targeting BCMA that obtained accelerated FDA approval in August 2020 but was later withdrawn from the market in November 2022. However, recent phase III clinical trials have re-demonstrated superior outcomes with belantamab-based regimens, and the drug is expected to make a comeback. Idecabtagene Vicluecel (ide-cel) is a BCMA-directed chimeric antigen receptor T-cell (CAR T) therapy that obtained FDA approval in March 2021.

Methods: In this single-center retrospective observational study performed at the University of Arkansas for Medical Sciences, we examined the outcomes with ide-cel in RRMM patients with and without prior exposure to belantamab. All patients who received ide-cel for RRMM on or before November 1, 2023, were identified. One patient had received BCMA-directed BiTE prior to ide-cel and was excluded from this study.

Results: 61 patients were included in our analysis. The median age at the time of ide-cel therapy was 66.6 years. Patients received a median of 8 (range: 5-15) lines of therapy prior to ide-cel therapy. All the patients received at least one immunomodulatory drug (IMiD), a proteasome inhibitor, and an anti-CD38 antibody. Patients had a median of two prior autologous stem cell transplants. Extra-medullary disease was present in 19 (31%) patients. 27 (44%) patients had at least one high-risk cytogenetic abnormality (HRCA).

22 (36%) patients received belantamab prior to ide-cel therapy. Patients received a median of 3 doses (range: 1-15). 9 (41%) patients had a partial response or better with belantamab. 17 (77%) patients reported keratopathy, with 9 (41%) patients developing grade 3 keratopathy. The median progression free survival (PFS) with belantamab was 8.1 months. The median time from belantamab use to CAR T was 5.5 (range: 2.23 - 25.89) months.

Patients had a median follow-up of 13.5 (range: 2.5-30.9) months after ide-cel therapy. 55 (90%) patients developed cytokine release syndrome (CRS), with grade 3 CRS in 3 (5%) patients. 9 (15%) patients developed neurotoxicity (NT), with grade 3 NT in 1 (2%) patient. Grade 3 or higher neutropenia, anemia, and thrombocytopenia were seen in 58 (97%), 28 (46%), and 41 (67%) patients, respectively. The incidence and severity of CRS and NT, the average number of days in the hospital and in the ICU, the need for tocilizumab, anakinra, steroids, the incidence and severity of cytopenias, and the need for stem cell boosts did not differ significantly between those with and without prior exposure to belantamab (p > 0.05).

At day 30, the overall response rate (ORR) was 41% in patients with prior exposure to belantamab, compared to 61% in patients without prior exposure to belantamab (p = 0.167). At day 90, the overall response rate (ORR) was 59% in patients with prior exposure to belantamab, compared to 82% in patients without prior exposure to belantamab (p = 0.088).

The median PFS with ide-cel for all patients was 12 months, and median overall survival (OS) was not reached at a median follow-up of 13.5 months. Patients with prior exposure to belantamab had a significantly lower median PFS of 10.3 months with ide-cel compared to 14.3 months in patients without prior exposure to belantamab (p = 0.049). Similarly, patients with prior exposure to belantamab had a significantly lower median OS compared to patients without prior exposure to belantamab (p = 0.036). Among patients who received belantamab, median PFS was significantly lower in patients who had a partial response or better with belantamab compared to patients with no response (p = 0.014). No similar difference was observed in overall survival (p = 0.55). PFS and OS did not differ significantly based on time from last dose of belantamab to CAR T-cell infusion.

Conclusions: Our study indicates that prior exposure to belantamab adversely affects the efficacy outcomes with ide-cel. Specifically, patients who respond to belantamab exhibit inferior outcomes with ide-cel compared to those not achieving a partial or better response to belantamab. With the potential re-approval of belantamab and the increasing availability of BCMA CAR T-cell therapy, understanding the impact of previous exposure to BCMA-directed therapies is crucial for optimizing treatment selection for these patients.