Treatment Decision-Making in Multiple Myeloma at First and Subsequent Relapses

The treatment landscape for patients with multiple myeloma has evolved significantly with the introduction of T-cell redirection therapies, fundamentally changing how clinicians approach treatment decisions. Patients consistently prioritize progression-free survival and treatment-free intervals when discussing therapy options, with many expressing strong interest in the “one and done” concept associated with chimeric antigen receptor (CAR) T-cell therapy. However, emerging data from the International Myeloma Society 2025 conference demonstrate that patients receiving bispecific antibodies may achieve sustained treatment-free intervals lasting several years even after early discontinuation, suggesting these therapies may not require indefinite administration.

When selecting treatments for patients with relapsed/refractory multiple myeloma, clinicians must consider multiple factors including patient age, comorbidities, frailty status, disease burden, genetic risk factors, and prior therapy exposures. The current regulatory landscape requires patients to have received at least 4 prior lines of therapy with triple-class exposure before accessing bispecific antibodies in the United States. However, clinical trial data increasingly support earlier intervention, with newly diagnosed patients achieving 100% response rates and minimal residual disease–negative status in studies like MajesTEC, potentially challenging the traditional role of CAR T-cell therapy.

The paradigm of diminishing returns with successive therapies has been fundamentally altered by T-cell redirection approaches. Historically, patients experienced progressively shorter remissions with each subsequent line of therapy, but bispecific antibodies are now delivering response rates of 60% to 70% with durable remissions lasting over a year in heavily pretreated patients who previously faced limited options. This represents a dramatic shift from the 20% to 30% response rates for 3 to 4 months that were previously considered acceptable for accelerated approval, highlighting the transformative potential of these novel immunotherapies for patients with advanced disease.