Multiple Myeloma Care Enters New Era of CAR T and Bispecifics, but Access and Extramedullary Disease Remain Hurdles

Multiple myeloma care is increasingly defined by the delivery of advanced T-cell–redirecting therapies, with experts emphasizing early evaluation for CAR T-cell therapy and highlighting both the promise and the persistent challenges of extramedullary disease. BCMA-targeted CAR T-cell therapy represents a major treatment advance for relapsed/refractory multiple myeloma, but access, sequencing, and high-risk subgroups remain central concerns.

According to experts, early evaluation is critical to determine patient suitability for CAR T-cell therapy, which may help identify those most likely to experience the greatest responses with minimal toxicity. Data have demonstrated the utility of administering CAR T-cell therapies prior to bispecific antibodies, and reassuring evidence indicates that patients who do not meet certain eligibility criteria may nevertheless benefit from CAR T-cell therapy. CAR T-cell therapy is now deeply entrenched in relapsed multiple myeloma and is likely to become entrenched in the newly diagnosed setting. Ongoing communication between academic and community clinicians is considered essential for optimal care.

Extramedullary disease (EMD) has emerged as a predictor of poor prognosis with CAR-T therapy. EMD is biologically aggressive, and patients with EMD generally see lower response rates and shorter remissions after CAR-T. Across real-world cohorts and subgroup analyses of landmark trials including KarMMa, CARTITUDE-1, KarMMa-3, and CARTITUDE-4, patients with EMD at the time of CAR-T infusion consistently achieve lower overall response rates, lower rates of complete response, and markedly shorter progression-free and overall survival compared to patients without EMD. This likely reflects a hostile extramedullary microenvironment, imperfect CAR-T trafficking and persistence outside the marrow, and antigen heterogeneity that enables antigen-low escape and relapse. EMD often co-exists with high-risk cytogenetics, high tumor burden, and systemic inflammation, contributing to early progression and potentially increasing toxicity risk. Researchers are exploring dual-target CAR-T approaches, trispecific antibodies, and combinations of bispecific antibodies directed at different targets; for example, the combination of teclistamab (BCMA×CD3) and talquetamab (GPRC5D×CD3) in the RedirecTT study has shown promising activity.

In newly diagnosed multiple myeloma, long-term follow-up from contemporary clinical trials has reinforced the importance of achieving deep responses while balancing efficacy, safety, and patient-centered treatment goals. The growing role of minimal residual disease assessment, ongoing therapy, and individualized treatment duration are areas of continued clinical interest. Treatment decisions should remain tailored to each patient's overall health status and preferences, with emphasis on shared decision-making, multidisciplinary care, patient education, and longitudinal follow-up.

The treatment landscape continues to expand beyond CAR T. The number of approved CAR-T products for multiple myeloma has grown from one to two, with a third expected soon. A new drug class, CELMoDs (cereblon E3 ligase modulatory drugs), targets the same protein and pathways as immune modulators but aims to do so more effectively, and is being evaluated in clinical trials. Results from the phase III MajesTEC-3 trial, combining the CD38-targeting drug daratumumab with the bispecific antibody teclistamab, have shown data at about 3 years that are comparable to those of the BCMA CAR-T product cilta-cel, prompting some clinicians to discuss the possibility of a functional cure. There is ongoing debate about sequencing—whether to use a CAR-T first or a T-cell–engaging bispecific before a CAR targeting the same protein.

Delivering these advanced therapies poses operational and financial challenges. Bispecific therapy requires a dedicated team, patient education, and 24-hour provider support. CAR T-cell therapy requires an even more dedicated system because of the acuity of side effects that can occur in the first 2 weeks of treatment; some patients need to be in close proximity to a hospital, requiring collaboration between inpatient and outpatient teams. Payers require discussion and education, and institutions must determine whether delivering these therapies addresses a high unmet need in their community. CAR T-cell therapy is becoming increasingly deliverable in the community setting, but that requires certification and ongoing conversations with payers to ensure quality standards and infrastructure investment.

Partnerships across health systems, pharmaceutical companies, community oncology practices, academic centers, and insurers are seen as a step toward reducing cost barriers and improving access. Value-based care requires aligning incentives to reduce financial toxicity and geographic friction, prioritizing delivery of complex services near patients' homes. However, numerous states and cities have few or no National Cancer Institute–designated cancer centers, limiting access to innovative therapies. Proposals to improve access include opening tumor boards to community and academic clinicians and fostering partnerships to commit that every patient who needs treatment receives it. The central question is not whether effective drugs exist, but how to deliver them to the vast majority of patients.