Choosing Wisely in First Relapse of Multiple Myeloma: Expert Insights on Treatment Selection

Although treatments have greatly improved outcomes in patients with newly diagnosed multiple myeloma (MM), most patients will relapse after initial therapy and require subsequent treatment. With the wide variety of available treatment regimens (including new combinations of approved therapies) and the need to tailor MM treatment based on disease- and patient-centric factors, it can be challenging to select an appropriate treatment at first relapse. This decision should also consider the effect of second-line therapy on future treatment options for eligible patients, particularly chimeric antigen receptor T-cell (CAR-T) therapy and other T-cell-engaging therapies (eg, bispecific antibodies) targeting B-cell maturation antigen or other tumor antigens. Treatment selection should prioritize therapies with the greatest survival benefit to reduce risk of attrition with subsequent lines of therapy. Key considerations include patient age, performance status, comorbidities, cytogenetics, prior drug exposure, and duration of response to initial therapy. Furthermore, early referral before CAR-T therapy is highly recommended to prepare for treatments received before apheresis (ie, holding therapy) as well as treatments received during CAR-T manufacturing, between apheresis and CAR-T infusion (ie, bridging therapy). The timing of referral for CAR-T therapy is critical, as CAR-T manufacturing may require 3-4 weeks or longer depending on product, during which time, disease progression may occur without effective bridging therapy. In this article, we provide insights from experienced physicians on approaches for optimizing second-line therapy in patients with MM who have relapsed after initial treatment.