Novel CAR T-Cell Therapies May Improve Outcomes Vs SOCs in Multiple Myeloma

CAR T-cell therapies have shown a lot of promise in the treatment of multiple myeloma, and at the 2025 National Immune Cell Effector Therapy (ICE-T) Conference, experts gathered to discuss the latest cellular therapy advances.

Barry Paul, MD, an assistant professor of Cancer Medicine at Levine Cancer Institute of Atrium Health Wake Forest University School of Medicine, told CancerNetwork® that the current standard treatment options remain chemotherapy-based regimens, but that CAR T-cell therapies offer a new pathway for high-level immune-based targeted agents.

Specifically, he highlighted 3 CAR T-cell agents that have shown promise thus far in multiple myeloma: ciltacabtagene autoleucel (cilta-cel; Carvykti), anitocabtagene autoleucel (anito-cel), and arlocabtagene autoleucel (arlo-cel).1

In the phase 1b/2 CARTITUDE-1 trial (NCT03548207), cilta-cel demonstrated a median overall survival (OS) of 60.7 months (95% CI, 41.9-not evaluable) and durable responses, with approximately a third of patients remaining in a complete response at 5 years after their infusion.2 Anito-cel demonstrated positive responses, notably in patients with high-risk extramedullary disease. Arlo-cel demonstrated similar efficacy to talquetamab-tgvs (Talvey), but with lower levels of toxicity.

Transcript:

We have lots of different options for our patients. We try to derive the best possible treatment for each specific patient based on their unique situation, their unique [multiple] myeloma, and what other comorbidities they may or may not have. Traditionally, we would offer a chemotherapy-based regimen that is a combination of immunotherapies and chemotherapies that target both the [multiple] myeloma cells directly, as well as the immune microenvironment. CAR [T-cell therapy] is a different way to address these types of patients in such a way that they are not necessarily getting chemotherapy, but they’re getting an immune-based targeted therapy that attacks the [multiple] myeloma at the highest degree.

I’m encouraged by the more recent data that were published for cilta-cel with the 5-year follow-up, with…[the median] OS being 60 months, or 5 years. Plus, [approximately] 33% of patients were still responding to cilta-cel and were still at a complete response 5 years after their infusion. This is the first time in a long time that those of us who work in multiple myeloma are talking about a possible cure…which is incredibly exciting. It would be wonderful to be able to tell a patient that they are cured. That’s a very encouraging finding.

The anito-cel data are provocative, with high response rates in patients with high-risk disease and extramedullary disease. [There are] lower risks of long-term toxicities than we were seeing with cilta-cel. It will be interesting to see if that continues to bear itself out with more follow-up.

Finally, [there are] the arlo-cel data, with the GPRC5D CAR [T-cell therapy]. GPRC5D is an incredible antigen target to be targeting based on the data for talquetamab, but the toxicity with talquetamab tends to be very challenging to manage. Arlo-cel has the potential to be just as effective, if not more so, than talquetamab with less toxicity. Those would be the ones I’m most excited about.

Reference

1. Paul B. Advances in CAR-T therapy for myeloma. Presented at: 2025 Immune Cell Effector Therapy Symposium; July 26, 2025; Orlando, FL.
2. Jagannath S, Martin TG, Lin Y, et al. Long-term (≥5-Year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. J Clin Oncol. Published online June 3, 2025. doi:10.1200/JCO-25-00760