(Multiple Myeloma) Is GPRC5D-Targeted CAR-T Cell Therapy Effective?

CAR-T Cell Therapy Targeting GPRC5D Antigen in Relapsed/Refractory Multiple Myeloma

From December 10–13, 2022, Susan Bal and colleagues from the University of Alabama at Birmingham presented results at the ASH 2022 Annual Meeting in New Orleans, Louisiana, from the CC-95266-MM-001 Phase 1 trial evaluating BMS-986393 (CC-95266) — a GPRC5D-targeted CAR-T cell therapy — in heavily pretreated relapsed/refractory multiple myeloma patients.

Trial Design

This open-label, multicenter Phase 1 trial enrolled 17 patients with relapsed/refractory multiple myeloma who had received multiple prior lines of therapy. Primary endpoints included safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D). The treatment sequence included screening and leukapheresis, bridging therapy if needed, followed by 3 days of lymphodepletion chemotherapy.

Patient characteristics at enrollment:

• High-risk chromosomal abnormalities: 47% (N=8)
• Extramedullary plasmacytoma: 47% (N=8)
• Prior BCMA-targeted therapy: 41% (N=7)
• Drug-resistant patients: 24% (N=4)

Efficacy Results

Of 14 evaluable patients, 12 (86%) demonstrated a response, including:

• 4/6 patients previously treated with BCMA-targeted therapy
• 3/5 patients previously treated with BCMA-targeted CAR-T cell therapy

Median duration of response at a median follow-up of 4.0 months was not yet reached.

Safety Profile

Grade 3–4 adverse events related to BMS-986393 (CC-95266) occurred in 65% of patients (N=11/17):

• Most common: neutropenia (41%) and thrombocytopenia (35%)
• Dose-limiting toxicity occurred in 2 patients (neutropenia, thrombocytopenia)
• Cytokine release syndrome (CRS): 65% (N=11/17; mostly Grade 1–2)
• Immune effector cell-associated neurotoxicity syndrome (ICANS): 12% (N=2/17; both Grade 1)

Conclusions

Based on the CC-95266-MM-001 trial results, Susan Bal and colleagues concluded that GPRC5D-targeted CAR-T cell therapy (BMS-986393) in heavily pretreated relapsed/refractory multiple myeloma demonstrated an excellent safety profile with mild CRS and ICANS, as well as promising antitumor activity. The therapy is expected to become a new treatment option for drug-resistant patients. Dose-escalation studies are ongoing, with updated data to be provided in the future.

Source: https://ash.confex.com/ash/2022/webprogram/Paper162395.html

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