Myeloma Immunotherapies Show Promise, but Access Barriers Persist

Four bispecific antibodies are now approved for relapsed or refractory multiple myeloma, producing response rates of roughly 60 to 70 percent in heavily pretreated patients. Unlike CAR T-cell therapy, these drugs are available off the shelf, but their initial two-week step-up dosing period requires close monitoring to mitigate cytokine release syndrome and neurotoxicity, effectively tying treatment to academic medical centers and creating barriers for rural patients. Meanwhile, separate research published this month in Blood demonstrates that the experimental drug mezigdomide can reverse T cell exhaustion, enhancing the potency of both CAR-T and bispecific antibody therapies in preclinical models. Additionally, longer-term data for the CAR T-cell therapy CARVYKTI indicate a significant survival benefit for patients with limited options.

The logistical challenge of step-up dosing for bispecific antibodies has concentrated administration at hospitals with the infrastructure to manage immune-related toxicities. Each of the four approved myeloma bispecifics carries a Risk Evaluation and Mitigation Strategy (REMS) requirement, a certification burden that does not apply to bispecifics approved for lymphoma or lung cancer. A panelist at a November 2025 stakeholder meeting noted that no community practices in their area were REMS certified for any myeloma bispecifics, despite willingness to administer them after the dose-escalation phase. Inadequate reimbursement for the staffing and coordination needed further deters community adoption, according to the chief operating officer of Highlands Oncology Group.

Despite these hurdles, recent data from the US Oncology Network, presented at the American Society of Hematology’s 2025 annual meeting, showed that rural clinics comprised 16.3 percent of patients receiving bispecifics within that network, compared to 9.8 percent of those not receiving bispecifics, suggesting some rural patients are gaining access. A separate ASH analysis of Medicare beneficiaries with lymphoma found rural patients traveled an additional 56 miles and about 54 minutes one way for bispecific therapy, though myeloma-specific travel disparities are less documented. To broaden access, consensus documents are emerging: a European Delphi consensus published in eJHaem outlines a framework for outpatient step-up dosing and transferring patients from academic to community centers, while a global roadmap in Frontiers in Oncology addresses practical implementation.

The potential of these immunotherapies may be amplified by mezigdomide, a cereblon E3 ligase modulator developed by Bristol Myers Squibb. In two companion papers in Blood, researchers from the Icahn School of Medicine at Mount Sinai, the University of Oxford, and Bristol Myers Squibb showed that mezigdomide can reprogram exhausted T cells by degrading the transcription factors IKZF1 and IKZF3, which maintain dysfunctional states. In bone marrow samples from patients with relapsed multiple myeloma, mezigdomide reduced populations of T cells expressing exhaustion markers like PD-1 and TIGIT. Preclinical models demonstrated that combining mezigdomide with CAR-T cells or bispecific T cell engagers led to deeper tumor clearance and improved survival. Early-phase clinical trials evaluating these combinations are ongoing, and researchers say reversing T cell dysfunction could improve both depth and durability of response, particularly for patients whose immune systems are weakened by prior treatments.

For some patients, CAR T-cell therapy has already been transformative. CARVYKTI, which received an expanded access designation from the FDA in 2024, involves genetically modifying a patient’s own T cells over two to three months. New longer-term data show the treatment extends survival in patients who historically had an average survival of less than a year. In a news report, a patient with a decade-long history of multiple myeloma described returning to hiking within two months of receiving CARVYKTI after multiple other therapies had failed. The physician overseeing her care noted that if CAR T-cell therapy can keep patients alive for 10 to 15 years without their cancer progressing, it effectively represents a cure.

As the field advances, the dual focus remains: expanding the reach of effective immunotherapies beyond academic centers and enhancing their potency through combination strategies. Whether through streamlined dosing protocols, reduced regulatory barriers, or T cell-reinvigorating drugs, researchers and clinicians are working to ensure that more patients with multiple myeloma can benefit from these therapies.