The treatment of younger patients with multiple myeloma (MM) is evolving with the emergence of novel quadruplet regimens and T-cell–redirected therapies, which are challenging the traditional role of autologous stem cell transplant (ASCT). As new data emerge, clinicians are rethinking how best to balance depth of response, long-term remission, and evolving treatment options in this patient group.

Traditionally, MM has been a disease of the older patient population. The median age at diagnosis is late 60s. However, at places like ours (ie, academic referral centers), we do also see a younger patient population. Here, anyone under the age of 65 years is considered “young.” At our institute, approximately 30% to 40% of patients with MM are under the age of 65, and these are the patients who have been traditionally considered for a transplant-based approach. With the advent of T-cell–redirected therapies, both bispecifics and CAR T-cell therapy, I think that this distinction is going to be less of a problem because these are extremely potent drugs, and they are extremely well tolerated in both younger and older individuals.

For more than 60 years, we have used ASCT, which involves giving high doses of chemotherapy and then rescuing patients with their own stem cells. That is the standard of care (SOC) for MM right now. If you look at the data in a younger patient population, ASCT follows induction therapy with quadruplet regimens—for example, daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRd) with a transplant, followed by consolidation therapy with D-VRd and maintenance with lenalidomide. There are similar data on isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd), where transplants are part of care.

However, in the MIDAS study, investigators asked the following question: In the era of quadruplet therapy, do we need a transplant? Patients who were measurable residual disease negative, meaning that fewer than 1 in 1 million cancer cells were detected using next-generation sequencing or flow cytometry, were randomized to transplant vs no transplant. Early data from this study show no difference in terms of progression-free and overall survival between patients who received a transplant vs those who continued with the quadruplet.

Another ongoing study, CARTITUDE-6, which is comparing D-VRd followed by CAR T-cell therapy and lenalidomide vs D-VRd followed by ASCT and lenalidomide in patients with newly diagnosed MM, is expected to have early readouts in 1 to 2 years. This is the first time we are really questioning the role of transplant and seeing whether transplants can be replaced with a T-cell–redirected treatment.

In 2026, younger patients with MM should typically be treated with a quadruplet. It should be an anti-CD38–containing regimen with a proteasome inhibitor and dexamethasone. At Mass General Brigham Cancer Institute, we use a carfilzomib-containing regimen because younger patients are fitter, they are able to tolerate treatment, and we get deep responses. Most data on quadruplet therapy are aligned with the data on ASCT, and that is our recommendation right now. Collecting stem cells and having a discussion with the patient regarding ASCT are critical. For people with high-risk disease, ASCT should be offered because your first remission is your best and longest remission. Right now, CAR T-cell therapy is only US Food and Drug Administration (FDA) approved in the second-line setting. So, unless you are in a clinical trial such as MIDAS or CARTITUDE-6, the SOC in this patient population would be quadruplet therapy followed by the consideration of ASCT.