Relapsed/refractory multiple myeloma (RRMM) is entering a new era, with newer immunotherapies improving outcomes and expanding what is possible for patients. Current CAR T-cell therapies and bsAbs are improving the depth and durability of response, and the next wave of innovation is aimed at making treatment more effective, safer, and more accessible.

The treatment for RRMM has radically changed over the last 2 decades, particularly over the last 2 to 3 years. When I started working with patients with MM more than 25 years ago, the expected survival was 1 to 2 years after diagnosis. We really only had 1 or 2 treatments at that time. Yet here we are, 25 years later, with an expected survival upwards of 10 years and approximately 20 new treatment options available. So, this has really transformed the way we think about this disease, moving it closer and closer to becoming a chronic—if not even curable—disease.

In the realm of RRMM, there has been an explosion of immunotherapy treatment options. Historically, there were very few options for these patients; the expected survival was short, and very intense regimens were used. The initial options were primarily monoclonal antibodies, but, more recently, CAR T-cell therapies and bsAbs have become available that engage a patient’s own immune system and do not require extensive or intensive therapy sessions. These 2 classes of agents have not only provided deeper and more durable responses but also allowed patients to have a more functional quality of life. Furthermore, ADCs have increased the portfolio of immunotherapy.

Of course, despite this incredible progress, many challenges remain. While current therapies are significantly more efficacious than those we have had in the past, MM remains incurable, and most patients eventually experience relapse or disease progression. CAR T-cell therapies and bsAbs also come with their own challenges, including novel toxicities such as cytokine release syndrome, neurological toxicities, and infections. ADCs also come with eye-related side effects. Although we have come a long way in improving these, treatment-related adverse events remain a significant challenge.

As we look beyond the targets that we are currently leveraging, novel antigen targets such as GPRC5D and FCRH5 may help overcome some of the efficacy limitations that we observe with current BCMA-directed therapies, including treatment resistance and disease relapse. We also continue to gain experience in mitigating and managing toxicities, and the next wave of immunotherapies currently in development is making safety a priority. However, several questions remain. Can we develop a safer CAR T-cell therapy that is just as effective? Can we advance in vivo CAR T-cell or allogeneic CAR T-cell approaches that help improve patient access? Can we develop antibodies with improved bispecific- or even trispecific-targeting activity with less off-target activity to enhance efficacy, reduce toxicity, lower infection risk, and reduce the overall treatment burden for patients with RRMM? These are the things that we are seeking to achieve as we evolve immunotherapy options in this space.

I think the take-home message is that the immunotherapies CAR T-cell therapy, bsAbs, and ADCs have dramatically improved the outcomes of patients with RRMM from an efficacy and safety standpoint, and they only stand to improve with continued research and development efforts.