Advances in BCMA-Targeting Therapies: Takeaways from ASH2024

This year’s ASH conference saw a significant focus on multiple myeloma. Arcellx's Gilead-partnered CAR-T therapy, anitocabtagene autoleucel was a major highlight. At a follow-up of 34 months, a single anito-cel infusion delivered early, deep, and long-lasting responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM). Remarkably, the complete response rate reached 79%. Importantly, the treatment demonstrated a manageable safety profile.^{[1, 2]}

However, notable advancements in BCMA-directed multiple myeloma therapies extend beyond CAR-T, with a focus on antibody formats.

An interesting update concerned ABBV-383, a T-cell engager developed by AbbVie following its acquisition of TeneoOne. Recent data highlight promising outcomes for ABBV-383 in combination with Darzalex and dexamethasone, yielding an overall response rate (ORR) of 70%, which rises to 82% at higher doses. This development builds on AbbVie's earlier report of a 57% ORR from ABBV-383 monotherapy trials and underscores AbbVie's commitment to this area.^{[3, 4, 5]}

Initial findings on EMB-06, a T-cell engager developed by EpiMab and subsequently licensed to Vignette Bio, were also presented ^[6].

Complementing these discussions of BCMA-targeted therapies, ASH also showcased updates on Bristol Myers Squibb's pipeline. This includes its immunomodulatory cereblon E3 ligase modulators (celmods), such as mezigdomide, golcadomide, and iberdomide, aimed at extending the legacy of its Celgene-derived multiple myeloma treatments. ^{[7, 8, 9, 10, 11]}

Beyond BCMA, BMS's anti-GPRC5D CAR-T candidate, BMS-986393, has demonstrated significant potential, with Phase 1 trials reporting an impressive 91% ORR among evaluable patients treated at the go-forward dose. These results have encouraged the initiation of the Phase 3 Quintessential-2 trial, scheduled to begin in early 2024. ^{[12, 13]}

This year’s ASH also explored the management of precancerous conditions like smoldering myeloma, a primarily asymptomatic precursor to active multiple myeloma. Discussions focused on whether aggressive treatments, such as CAR-T therapy, are appropriate for managing these cases. The therapy's risks are highlighted by a study of Carvykti showing severe neutropenia in all patients and liver enzyme elevations in a subset ^[14]. Johnson & Johnson and Genmab’s Darzalex has shown promise in treating smoldering myeloma, with significantly improved progression-free survival compared to active monitoring (hazard ratio 0.49, p<0.0001) ^{[15, 16]}. Sanofi’s Sarclisa, also targeting this condition, is progressing through trials ^[17].

ASH 2024 delivered critical updates on these advanced clinical trials and therapies. The intersection of novel treatment modalities and evolving clinical strategies ensured the central role of this year's conference to the ongoing innovation in multiple myeloma and related indications.

Champions Oncology offers a cohort of patient-derived primary multiple myeloma models for use in our ex vivo Hematological Vitroscreen. These extremely rare and well-annotated models can help advance your multiple myeloma research and accelerate your drug pipeline.