In transplant-eligible, standard-risk patients with multiple myeloma (MM), autologous stem cell transplant followed by maintenance therapy has been considered the standard of care. Evolving areas are the incorporation of multiagent biologic therapy in pretransplant induction and maintenance therapy regimens, the potential for fixed-duration maintenance therapy, and the potential for transplant deferral.

Maintenance therapy after autologous stem cell transplant for MM is an evolving area, and many questions are being explored in clinical trials. Based on initial study experience, lenalidomide maintenance as fixed- or continuous-duration therapy was shown to have a significant impact on progression-free survival (PFS) and overall survival in some settings. Recently, the idea of primary therapy intensification has emerged, including with the use of daratumumab for CD38-directed antibody therapy as part of pretransplant induction and posttransplant maintenance strategies. Phase 2 data have been very promising in terms of PFS and depth of response, with high numbers of patients achieving measurable residual disease–negative responses. The impact of achieving measurable residual disease negativity on long-term outcomes has been observed across many studies. Persisting questions regarding maintenance therapy include the potential role of fixed-duration maintenance therapy in patients achieving deep responses, the relative impact of combination therapy on subsequent therapeutic treatment lines, and whether patients achieving maximal response prior to transplant may have their transplant deferred. Determining the correct approach in high-risk patients who tend to demonstrate shorter-duration responses to transplant and maintenance therapy also remains a challenge.

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Additionally, in real-world practice, the use of maintenance therapy is also impacted by toxicities and quality-of-life issues that limit the use of chronic therapies. For example, lenalidomide-associated diarrhea may be a challenge for ongoing use in this setting. Proteasome inhibitors are also an option for patients with MM, particularly those who cannot tolerate lenalidomide. I have used them in the second-line setting, although this is not my primary approach. There are many different maintenance therapies available, and practice is evolving with the knowledge that there may be more than one way to approach it.

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Another question is: What should you use next when sequencing treatment for MM? For example, the incorporation of multiple agents as part of first-line therapy may alter choices once patients experience disease relapse. Of note, novel immunotherapies such as CAR T cells and T-cell engagers have demonstrated dramatic responses in later lines of therapy, and their role early in therapy, including as a potential alternative to transplant, is being explored. We are living in a wonderful time because we have many different options, but this can also cause confusion because the algorithms are more complicated with so many treatment choices and potential sequences. The MM field is using a combination of evidence from larger trials as a guide and an evidence-based approach, but tailoring and individualizing treatment are quite important.