Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for relapsed and refractory hematologic malignancies, including multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL). However, the decision to offer CAR T-cell therapy requires careful consideration of patient-specific factors to maximize therapeutic benefit and minimize toxicity.1
Identifying Ideal Candidates for CAR T-cell Therapy
CAR T-cell therapy is most appropriate for patients with relapsed or refractory disease who have exhausted other lines of therapy, including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies.1 Ideal candidates often have good functional status, and adequate organ function to tolerate treatment-related toxicities such as cytokine release syndrome (CRS).1
Conversely, patients with poor performance status, active infections, significant cardiovascular or pulmonary comorbidities, or uncontrolled central nervous system involvement may not be suitable for CAR T-cell therapy.1,2
Optimizing CAR T-cell Therapy
In high-risk MM patients, relapse following anti-BCMA CAR T-cell therapy is frequent. Subsequent therapy including the use of selective inhibitors of nuclear export (SINEs), such as selinexor, present an emerging option in these high-risk patients.1,2 By targeting exportin 1 (XPO1), selinexor restores the nuclear localization of tumor suppressor proteins, promoting apoptosis and enhancing immune responses against tumor cells. Carfilzomib- and venetoclax-based therapies have also shown promise in patients with relapsed/refractory MM.2
Unlocking the Future of CAR T-cell Therapy
Optimal patient selection is critical to the success of CAR T-cell therapy, with considerations extending beyond disease stage to include performance status and comorbidities. The integration of other MM therapies into treatment protocols represents a promising approach to enhance CAR T-cell therapy efficacy, offering renewed hope for patients with limited therapeutic options, and paving the way for more effective, personalized treatments in the future.1,2
Take our Multiple Myeloma quiz to see how your knowledge compares to your peers.
