IMS 2025: Future Directions for CAR T Therapy in Relapsed and Refractory Multiple Myeloma

In an interview with Pharmacy Times®, Rahul Banerjee, MD, FACP, assistant professor of medicine at the Fred Hutchinson Cancer Center in Seattle, Washington, discussed the promise of CAR T therapy in relapsed and refractory multiple myeloma, highlighting long-term remissions seen in trials but also emphasizing limited patient access as a major unmet need. He highlighted his presentation, “Addressing unmet needs in RRMM: new therapies in development," which he shared at the 22nd annual International Myeloma Society (IMS) meeting and exposition in Toronto, Canada.

Banerjee noted that future goals include improving cure rates and addressing relapses after CAR T. Emerging therapies under investigation include dual-targeting CAR Ts, non–CAR T agents such as cell mods and protein degraders, and the re-emergence of belantamab. He explained that these therapies introduce novel mechanisms of action that may enhance T-cell function, reduce toxicities, and expand treatment options beyond BCMA-based approaches.

Pharmacy Times: From your perspective, what are the most significant unmet needs that still exist in the treatment of relapsed/refractory multiple myeloma (RRMM)?

Rahul Banerjee, MD, FACP: Many of the debates and topics being discussed today involve CAR T therapy. Earlier this year, for example, data from CARTITUDE-1 showed that 33% of patients are alive and disease-free five years after CAR T. That is amazing and really impressive, and that’s what we need in myeloma. People are already calling that a cure. I don’t know if I’m quite there yet—there will be a whole summit about that later. But 33% of people achieving cure is remarkable.

I think the future direction, number one, is increasing that number to 60–80%. Second, what are we doing for post-CAR T relapses? On the other side, the denominator matters. In that study, patients who received CAR T therapy had a median of six prior lines of treatment and happened to get access through a trial, even in the U.S. Many patients do not have access to CAR T. Practically, they may meet the criteria for cilta-cel after one prior line or ide-cel after two prior lines, but getting a patient through CAR T is a lot. There are many clinical, patient-specific, logistical, and disparity-related factors that make it very hard to access.

I would say that is the biggest unmet need. CAR T therapy is doing so much for patients, but it is not available to many of them. Around the world, CAR T is not available to the vast majority, and that unmet need must be addressed.

Pharmacy Times: Which novel therapeutic classes or agents in development do you believe have the greatest potential to change the treatment landscape?

Banerjee: In terms of the most promising therapies on the horizon, I would divide them into two categories: CAR T and non–CAR T.

For CAR T-cell therapy, data are being presented with an investigational BCMA therapy called anitocabtagene (Anita-cel). It may work as well as cilta-cel and possibly have fewer delayed neurotoxicities, such as nerve palsies or Guillain-Barré syndrome. These are rare, but Anita-cel may reduce them further. That’s exciting.

Other dual-targeting CAR Ts are also being studied. Ida-cel and cilta-cel both target BCMA, but newer constructs also target another antigen, making it harder for myeloma cells to escape. One example is AZD0120, formerly GCO-2F, which targets both BCMA and CD19. Listeners may know CD19 CAR T for lymphoma—here it is added alongside BCMA to prevent relapses from myeloma stem or progenitor cells that resemble lymphoma cells.

On the non–CAR T side, several things are noteworthy. Cell mods, such as iberdomide and mezigdomide, are showing a lot of promise. Novel protein degraders, such as CC-92480, are also being presented. Another major development is belantamab. Many know belantamab—it was on the market, pulled, then reapproved in Europe and Canada. The FDA is taking its time in the U.S. I would not give belantamab to someone eligible for BCMA CAR T, but for patients who are not candidates due to logistical or clinical reasons, belantamab can be amazing. Its eye toxicities can be managed with modifications.

Pharmacy Times: How do these emerging therapies differ in terms of mechanisms of action compared with currently available options?

Banerjee: I’ll break this into CAR T and non–CAR T therapies.

For CAR T, dual-targeting constructs are being studied, such as those targeting BCMA plus another antigen. Data are being presented with Arlo-cel, a GPRC5D-targeting CAR T. This is particularly interesting because it is not BCMA-based, so it can work in both pre- and post-BCMA settings. Another advantage is that it may cause fewer infections than BCMA CAR Ts, since GPRC5D (also targeted by the bispecific talquetamab) is not as widely expressed on normal plasma or B cells.

On the non–CAR T side, several novel agents are in development. The cell mods iberdomide and mezigdomide are similar to prior-generation IMiDs (lenalidomide, pomalidomide) but act more potently on proteins like Ikaros and Aiolos. They not only target myeloma more effectively but also improve T-cell fitness, which may enhance responses to bispecifics and CAR T.

Beyond that, newer mechanisms are emerging, such as bromodomain inhibitors like INCB057643, which are still in early-phase studies. These represent entirely new mechanisms of action, though more data are needed to understand their potential.