<p>There is a wider range of newer agents that are now available for the treatment of relapsed multiple myeloma (MM). However, these agents are associated with novel toxicities that require a careful approach to management and supportive care.</p>

People with MM are living longer, and they experience sequelae of both their disease and the therapies that we give them. Reducing infection risk and maintaining bone health remain challenging, and infections and bone-related issues need to be monitored for and managed in a prospective, mindful fashion. Newer immunotherapies may increase the likelihood of infection, so the use of prophylactic antimicrobials to prevent infection and intravenous immunoglobulin to treat hypogammaglobulinemia has become more common. We must also be mindful of the on-target, off-tumor effects that can occur with certain therapies, such as those directed at GPRC5D, that may affect the skin, nails, and oral cavity. We are still learning how to manage these toxicities.

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In the future, we will have more treatment options, so how might we, one day, successfully combine novel therapies such as CELMoDs or ADCs with the treatments that we currently have? We will have to mix and match according to the safety profiles, and I think that quality-of-life considerations and toxicity management will become even more important. Additionally, how might we mitigate side effects? Can we come up with alternate treatment schedules or give fixed-duration treatment to prevent long-term side effects?

I think about this all the time for patients with MM who experience amazing responses to treatment. These individuals would like to stop therapy and really enjoy life, but we are not there yet in MM. In contrast, patients who are being treated for lymphomas may experience a lot of toxicity for 6 cycles, but then they stop therapy.

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Over the past 15 to 20 years, there have been advances in achieving measurable residual disease negativity, but we still continuously give people therapies with toxicities. Even maintenance therapy with lenalidomide can cause toxicity, including mild toxicities such as diarrhea, which may seem like nothing to us but are problems for our patients. In fact, just staying on a pill every day can be challenging for them. Some treatments increase the risk for infections when they kill both normal and malignant plasma cells. The continuous push of immunotherapy can lead to immune system dysfunction and the neurotoxicities that are seen with the use of CAR T-cell therapy and other treatments. Within the next 5 years or so, I would like for us to be able to tell our patients when they will be able to stop therapy to allow them to recover and enjoy life.

I would add that there are 2 ways in which we approach toxicity in MM. One is learning how to mitigate, treat, and/or avoid side effects. That might include boosting immune function with antimicrobial prophylaxis or intravenous immunoglobulin or using supportive care to avoid or mitigate toxicities. We also need to consider the treatment schedule. Are we giving patients periods during which they may have a break from therapy?

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Moreover, there are patients with more indolent disease who would probably benefit most from a much lighter therapeutic touch and others who really require more intensive approaches. There is certainly an appeal to the idea of driving everyone with MM into maximal response, but that really needs to be weighed against the overall arc of their disease, their experiences, and the side effects of therapy. The treatment of MM requires the art of medicine rather than just an algorithmic approach.