Immunotherapies such as CAR T-cell therapy and bispecific antibodies are a substantial advance in the treatment of relapsed/refractory multiple myeloma. Our featured experts review the current role of these treatment options and address existing challenges and future areas of study.

The treatment of multiple myeloma has changed so much over the past several decades, which Dr Anderson can attest to. Over the last few years in particular, we have seen the introduction of new immunotherapies, including CAR T-cell therapy and bispecific antibodies. We already had effective agents such as proteasome inhibitors, IMiDs, and monoclonal antibodies targeting CD38. Combinations of these regimens have provided very durable responses for patients with multiple myeloma during the first 2 to 3 lines of therapy. Unfortunately, we are dealing with a disease that invariably becomes resistant or refractory to all of these treatments. Patients are left with very few treatment options to control their disease.

This is where CAR T-cell therapy and bispecific antibodies have made a dramatic difference for patients. These agents act by engaging the patient’s own immune system. Bispecific antibodies bring T cells to the tumor, and CAR T cells modify T cells to target the multiple myeloma cells. We are now able to kill multiple myeloma cells in a very effective manner and to provide very deep responses that were not previously observed in this patient population. These are not only deep responses but also very durable responses.

Right now, we are using these therapeutic options in patients whose multiple myeloma has become refractory to the other available treatments. I think that this will continue to change as new data come in, and it is likely that we will start moving these immunotherapies into earlier lines of treatment.

These are exciting times for multiple myeloma. We are certainly seeing patients who are living a lot longer compared with what we have seen in the past, but it is up to the multiple myeloma community to determine why some patients eventually become resistant to these therapies so that we can continue to improve them.

I agree with Dr Kumar’s assessment of the current role of these treatment options. Currently, bispecific antibodies are used in patients whose multiple myeloma has become refractory to at least 4 prior lines of therapy, including IMiDs, proteasome inhibitors, and anti-CD38 antibodies. As Dr Kumar explained, bispecific antibodies have demonstrated remarkable response rates and durable responses in lines of therapy where we lacked other treatments. They have also expanded our ability to treat older patients and those with poorer performance statuses and have really improved their overall outcomes. CAR T-cell therapies are US Food and Drug Administration (FDA) approved in the same lines of therapy, but we are now able to move CAR T-cell therapies to earlier lines of therapy, expanding access to these very effective agents.

This brings up the topic of challenges in accessing these therapies. We are seeing better penetration and improvements in the ability to give bispecific antibodies in the community-based setting, a greater availability of CAR T-cell therapy in specialized centers, and more access to manufacturing slots. But it is true that these treatments still do not reach all of our patients. Access is key, and we need to ensure that the knowledge and availability are there so that everyone with multiple myeloma has equal access to these wonderful treatment advances.

I could not agree more with Dr Kumar and Dr Huff. I believe that we have had what I would call an immune revolution in multiple myeloma treatment due to the availability of CAR T cells and bispecific T-cell engagers. As was true of the prior treatments for this disease, these new options have now been tested and are proven to be remarkably effective in patients with very advanced disease. The majority of patients who have had 4 or more prior treatments respond very deeply, with measurable residual disease–negative responses. In some cases, these responses last many years. It is exciting that we are achieving responses that are durable, which was not the case in the past.

As previously mentioned, both CAR T-cell therapy and bispecific T-cell engagers are now being moved to earlier in the disease course, when a patient’s performance status is better and they have less refractory disease. Recent data in earlier relapsed multiple myeloma suggest that the frequency, extent, and durability of response are superior to FDA-approved relapsed multiple myeloma therapies. I would add, however, that we need to continue to evaluate the objective data from these clinical trials very carefully, not only in terms of efficacy and long-term durability but also in terms of adverse events. Ongoing clinical trials are now evaluating whether the therapeutic index for these new agents is superior to current therapies when used to treat newly diagnosed and even smoldering multiple myeloma, and we eagerly await the results of these studies. It is truly an unprecedented time in multiple myeloma, and patients have more options than ever before. Importantly, and as Dr Huff mentioned, we need to make sure that access to these advances is equal for all of our patients.