Advances in combination therapy and immunotherapy are improving outcomes in multiple myeloma (MM). Achieving deep responses early on and personalizing treatment remain key strategies for extending remission and survival.

In MM, we have multiple drugs with excellent single-agent activity, and, in combination, they have led to better overall response rates, depths of response, and measurable residual disease (MRD) negativity rates. Two things that I think we need to avoid are delays in controlling the disease and complications. I focus on a few pillars: disease risk, patient fitness/comorbidity, prior therapy exposure, and patient goals. Treatment must be based on a clear plan of induction, consolidation (when appropriate), and maintenance that provides sustained response and maintains quality of life.

At diagnosis, it is important to use an effective combination that is individualized to the patient’s needs and disease characteristics, provides the deepest response, and is tolerable. Achieving excellent control of MM early on provides better progression-free survival, overall survival, and quality of life. In the third or fourth line, the response rate is lower, and the duration of response is shorter. Four-drug regimens have proven effective in both transplant-eligible and -ineligible patients, with monoclonal antibodies, immunomodulatory drugs, and proteasome inhibitors in combination providing the best results. The days of sequencing or using 2 drugs are probably behind us—you are not going to “win” by not getting a deep response.

The buzzword in MM today is “immunotherapy,” and we have many options for relapsed/refractory MM (RRMM) with some exciting, relatively recent advancements. For example, CAR T-cell therapy is now indicated at first relapse, and bsAbs are being used in combination with existing monoclonal antibodies in early relapse.

CAR T-cell therapies are US Food and Drug Administration (FDA) approved for the treatment of RRMM after 2 or more prior lines of therapy (ie, idecabtagene vicleucel) and at first relapse in patients with 1 prior line of therapy (ie, ciltacabtagene autoleucel). Because patients who are relapsing or progressing do not do well on CAR T-cell therapy, they need to be seen early on and, ideally, at a center that offers CAR T-cell therapy so that there is care coordination.

bsAbs are one of the most important therapies available today. They provide deep responses and progression-free survival at third and fourth relapses. Unfortunately, bsAbs are often not given due to treatment-related side effects such as cytokine release syndrome, neurotoxicity, and infections. However, most cytokine release syndrome and neurotoxicity events are low grade and manageable, and there are great guidelines for managing infections. bsAbs are important drugs, so I really hope that more patients in the community can gain access to them.

Another option in the RRMM setting includes ADCs such as belantamab mafodotin. Belantamab mafodotin is back on the market based on the stronger combination-based data from DREAMM-7. It does not require step-up dosing, allowing for the immediate access to treatment. Many of my patients have benefited from this drug—even having lasting responses despite not being on therapy—and, with close monitoring, you can provide excellent disease control with minimal ocular toxicity.

Overall, it is important to achieve the best outcome for our patients with MM early on in the disease course because the sooner we achieve a complete remission and MRD negativity, the better we serve our patients.