Treating relapsed/refractory multiple myeloma (RRMM) outside the clinical trial setting requires navigating numerous factors that are underrepresented in study populations, including older age, comorbidities, access barriers, and more complex disease features. Real-world care requires treatment approaches and dosing strategies that are not only effective but also practical and deliverable for the patients who are most often seen in practice.

The lack of representation of RRMM in clinical trials can make it difficult to extrapolate clinical trial results to real-world applications. Patients who are often underrepresented in clinical trials include older patients and/or those with frailty, patients with comorbidities, those who lack access to academic centers (ie, rural populations), and underserved patient populations, such as Black patients. From a disease perspective, certain subtypes of MM are also often underrepresented in clinical trials, including aggressive/high-risk disease, plasma cell leukemia, central nervous system MM, and/or nonsecretory MM/extramedullary disease. The same is true for treatment. Having access to an academic center is required for many treatments. Treatment outcomes can also vary depending on a patient’s caregiver support and health literacy, among other factors.

When translating clinical trial results into real-world applications, we should also consider how we develop drugs. For patients with unmet needs who cannot wait 5 years, for example, for randomized studies to read out, accelerated approvals provide an invaluable lifeline of earlier access to novel therapies with promising activity. However, maximum tolerated doses are determined in phase 1 trials and then studied further in phase 2 trials, leading to accelerated approvals. The problem with this process is that it puts such an emphasis on efficacy without considering longer-term safety and deliverability. Historically, in MM, several agents were initially approved by the US Food and Drug Administration (FDA) in very dose-intense schedules, but, ultimately, these schedules are not easily deliverable in the real world.

In 2025, some exciting data were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition from LimiTec, which is an ongoing phase 2 clinical trial investigating limited-duration therapy with the BCMA-targeted bsAb teclistamab in patients with RRMM. In this trial, investigators provided the recommended phase 2 dosing, but if patients had a good response after 6 to 9 months, they were allowed to stop therapy. Results from this interim analysis showed that limited-duration treatment with teclistamab led to a median progression-free survival of 19.9 months, which compares favorably with continuous treatment in the MajesTEC-1 trial (albeit this study was more impacted by COVID-19 and was the first BCMA bsAb study providing invaluable lessons about infection mitigation strategies that have benefited all subsequent BCMA-targeting TCEs). This tells us that we may not need to continuously treat all patients with RRMM with bsAb therapy until disease progression.

Through Project Optimus, the FDA has really been pushing for more thoughtful dosing selection (for example, patients are randomized to a dose-dense option A or a less dose-dense option B). This way, we can determine the optimal balance of efficacy and safety. In the real world, patients treated with dose-intense therapies have to frequently skip or delay treatment due to adverse events. So, why not be more thoughtful about selecting the right dose even for accelerated approvals, especially that we now also have measurable residual disease as a surrogate for progression-free survival? I think that this is probably one of the most significant unmet needs we have right now in RRMM.

Overall, we need to make sure that diverse patients and disease subtypes are well represented in clinical trials with thoughtful dosing schedules so that FDA-approved regimens are actually deliverable to real-world patients and confer comparable benefits to those attained in studies.