The treatment armamentarium for relapsed/refractory multiple myeloma (MM) continues to grow. Real-world data provide an opportunity to understand the impact of treatments in a wider array of patients compared with clinical trial data and to confirm the appropriateness of treatment strategies for patients with frailty or comorbidities who may not have been represented in clinical trials.

After clinical trials are completed and a drug is US Food and Drug Administration (FDA) approved and on the market, the following question arises: “What happens if I treat someone with MM who has renal insufficiency, has frailty, or is in a different age group than patients in the trials?” This is an important question, and this is where the real-world data matter a lot. Real-world data give us a better sense of the safety and response profile of a drug and a better sense of which patient populations—outside of the very strict enrollment criteria of the clinical trials—can tolerate a treatment.

<br>

The most exciting work is being done in the relapsed MM setting with CAR T-cell therapy and bsAbs. There is a lot of excitement about understanding how we can use these agents in the real world and about what their limitations are. For idecabtagene vicleucel (ide-cel), for example, the authors of a 2023 analysis of 159 patients with relapsed/refractory MM reported a similar response rate and progression-free survival to that of patients in the KarMMa trial. This gives us confidence that people who may not have met the enrollment criteria for KarMMa are still capable of receiving therapy.

<br>

A similar analysis was done for patients with relapsed/refractory MM receiving ciltacabtagene autoleucel (cilta-cel), with researchers reporting lower efficacy but a similar toxicity profile to that reported in the CARTITUDE-1 trial. Another recent analysis of patients receiving cilta-cel showed somewhat lower efficacy, higher nonrelapse mortality, and delayed neurotoxicity.

<br>

Yet another recent analysis looked at cilta-cel and ide-cel in patients with relapsed/refractory MM and renal impairment. Patients in the study responded well to CAR T-cell therapy, although their rates of immune effector cell–associated neurotoxicity syndrome and infection were higher compared with the control group. The most interesting data are from a recent real-world, head-to-head comparison of cilta-cel vs ide-cel. Now, this was a small retrospective trial, but the overall response rate with ide-cel was lower compared with cilta-cel, giving us the sense that the real-world data are representative of the clinical trials.

<br>

Similarly, for the bsAbs teclistamab, talquetamab, and elranatamab, real-world data provide us with insights for practice. For teclistamab, we see that real-world experience with cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and infection is similar to that seen in clinical trials. We are learning that we may need to use intravenous immunoglobulin to treat and potentially prevent cytokine release syndrome in the outpatient setting. Response rates and toxicity profiles with talquetamab and elranatamab from real-world studies have been similar to data reported in the clinical trials that led to their FDA approvals. This gives us confidence that we can use bsAbs in the community and expect high response rates. This is all information that we would not have learned from clinical trials alone.