Optimal Sequencing Between CAR T and Bispecifics in Multiple Myeloma

Meet the experts

A recent Training Academy discussed the use of chimeric antigen receptor (CAR) T-cell therapy and other sequencing options for patients with multiple myeloma. Additionally, the phase 3 CARTITUDE-4 trial (NCT04181827) was discussed, and the efficacy and safety outcomes showed a positive trend with CAR T-cell therapy.

CARTITUDE-4 Trial

• Assessed ciltacabtagene autoleucel (cilta-cel, Carvykti) or physician’s choice standard of care (SOC) in patients with lenalidomide (Revlimid)–refractory relapsed/refractory
  multiple myeloma.
• Efficacy:
  • The median follow-up was 15.9 months.
  • Median progression-free survival (PFS) was not reached in the cilta-cel group vs 11.8 months in the SOC group (HR, 0.26; 95% CI, 0.18-0.38; P < .001).
  • At 12 months, the PFS rate was 75.9% (95% CI, 69.4%-81.1%) vs 48.6% (95% CI, 41.5%-55.3%).
  • The overall response rate was 84.6% vs 67.3%, complete response or better was 73.1% vs 21.8%, and 60.6% vs 15.6% had an absence of minimal residual disease.
• Safety:
  • Grade 3 cytokine release syndrome (CRS) was observed in 76.1% of patients in the cilta-cel arm, 1.1% had grade 4, and none had grade 5.
  • Other grade 1/2 adverse effects included immune effector cell–associated neurotoxicity syndrome (ICANS; 4.5%), cranial nerve palsy (9.1% vs 8.0%), and CAR T–related neuropathy (2.8% vs 2.3%).

Voorhees / What is the optimal sequencing for CAR T-cell
therapies and bispecific antibodies?

Grajales-Cruz / Social support when deciding on CAR T is crucial because we know that for CAR T, you need social support. You need a caregiver who can assist. My personal preference, if possible, would always be BCMA [B-cell maturation antigen] and CAR T first, followed by a bispecific. In reality, I’m ambivalent in terms of which target [to use]. It could be BCMA or GPRC5D, based on the responses that we might have seen, the performance status, and patient preference. We don’t have a head-to-head comparison between the 3 approved agents [talquetamab-tgvs (Talvey), teclistamab-cqyv (Tecvayli), and elranatamab-bcmm (Elrexfio)] to say one is better.

Martin / We are gravitating toward those patients who are going to be CAR T-cell patients. They’re getting them in earlier lines of therapy. We’ll see data over time that it is resulting in less anxiety from me and my support team that are we going to be able to get the patient to the CAR T because their disease is wrapping up, but also less adverse effects with the CAR T cell, because patients are going into the CAR T with low disease burden. We’re seeing less CRS, and we’re seeing less ICANS, and hopefully, we’re going to see better PFS. That’s going to be decided by the long-term results with updates of CARTITUDE-4.

Kumar / The most important thing is getting more data in terms of sequencing. The drop that we see in the CAR T efficacy going from bispecifics to CAR T vs the drop in the efficacy in the bispecifics points toward what we talked about. It’s always better to use the CAR T early. Also, how early is early? That’s where the challenge comes in terms of the first relapse in patients who are, in other ways, doing well. How do we balance the potential for toxicity, many of which we are continuing to lean to the CAR T-cell therapy, vs more time-tested regimens, which are associated with continuous therapy but good efficacy?

Reference

San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379