Multiple myeloma, a cancer of plasma cells in the bone marrow, is treatable but generally not curable. There are several existing therapies that can bring the disease into a state of remission, but eventual relapse is a common, if not expected, outcome.
It is not uncommon for patients to receive upwards of four different lines of therapy over the course of disease. The development of new drugs provides more treatment options for patients who continue to relapse, therapy after therapy. Immunotherapies, that boost immune function specifically against the malignancy, can be effective in in cases where the cancer continues to relapse with conventional therapies
Elranatamab is a relatively new immunotherapy therapy for multiple myeloma, approved for use in the United States in 2023. It is a bispecific antibody with binding specificity to both the BCMA protein, exclusively expressed on plasma cells, and the CD3 protein expressed only on T cells. Elranatamab acts as a bridge, bringing the cancer-fighting T cells directly to the cancer cells.
Elranatamab showed promising efficacy in the phase 2 MagnetisMM-3 trial, which enrolled high-functioning patients without a history of receiving targeted immunotherapies. Current use of elranatamab, however, includes patients that would have fallen outside of the trial eligibility, often because of prior BCMA-targeted immunotherapies or high burden of disease.
In a recent study published in Blood Cancer Journal, Dr. Andrew Portuguese in the Clinical Research Division and colleagues in the U.S. Multiple Myeloma Immunotherapy Consortium examined the safety and efficacy of elranatamab in its real-world use. The team performed a retrospective analysis of 130 patients who received elranatamab across nine academic medical research centers in the United States. Only 22% of these patients would have met the inclusion criteria for the MagnetisMM-3 trial. Overall, the real-world patient population was more heavily pre-treated and presented with more severe disease than the trial patient population.
In the real-world cohort, 65% of patients treated with elranatamab saw a reduction in disease burden. The median progression-free survival, however, was only 4.3 months, and the median overall survival was just 14.6 months. The MagnetisMM-3 trial also saw a response rate of 65%, but showed superior survival outcomes, with a median progression-free survival of 17.2 months and overall survival of 24.6 months. Dr. Portuguese commented, “Although the response rate remained meaningful, the durability of benefit was substantially shorter in routine practice, with a median progression-free survival of only 4.3 months compared with 17.2 months reported in MagnetisMM-3. This gap highlights an important knowledge deficit: clinical trials may not fully capture how BCMA-directed bispecific antibodies perform in the frailer, more heavily pretreated, and more biologically high-risk patients we commonly treat in practice.”
The study identified several correlates of elranatamab treatment success. Patients with higher hemoglobin levels saw improved response and survival, while patients with higher lactate dehydrogenase (LDH) – an essential metabolic enzyme that has elevated levels in cancers like multiple myeloma – or a higher burden of disease in the bone marrow had more limited responses. Put simply, more advanced disease was associated with poorer outcomes.
“These findings suggest that elranatamab should not be viewed as a uniformly durable option for all patients with relapsed/refractory myeloma, but rather as a therapy whose benefit may depend strongly on disease biology, timing, prior treatment exposure, and supportive care,” noted Dr. Portuguese.
The study also provided information on elranatamab safety in routine practice. There were high rates of over-activated immune response adverse effects like cytokine release syndrome (39%) and immune effector cell-associated neurotoxicity (17%). Post-treatment infections were also common, occurring in 38% of patients. The frequency of these adverse events highlights the need for including prophylactic and supportive care measures to prevent dangerous treatment side effects.
Dr. Portuguese said, “Going forward, our research will focus on improving patient selection, understanding why durability is limited in high-risk real-world patients, and developing strategies to personalize bispecific antibody selection and sequencing to make these therapies safer and more effective in routine clinical practice.”
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Member Drs. Andrew Portuguese, Danai Dima, Rahul Banerjee, and Emily Liang contributed to this research.
There was no dedicated funding for the spotlighted research.
Portuguese AJ, Davis JA, Raza S, Castaneda Puglianini O, Freeman C, Alsina M, Wright C, Blue BJ, Baz RC, Shain KH, Goel U, Khouri J, Anwer F, Ali HM, Pasvolsky O, Gaballa M, Patel K, Garcia-Pleitez H, Mikulski D, Fogel L, Zolotov E, Sannareddy A, Afrough A, Anderson LD Jr, Julian K, Dima D, Banerjee R, Liang EC, Cassano Cassano R, Herr MM, Hassan H, Shune L, Kort J, Midha S, Nadeem O, Sidana S, Lin Y, Locke FL, Hansen DK, Sborov D, Biran N, Grajales-Cruz A. 2026. Real-world outcomes with elranatamab in multiple myeloma: a multicenter analysis from the U.S. Multiple Myeloma Immunotherapy Consortium. Blood Cancer Journal. doi: 10.1038/s41408-026-01477-z
Science Spotlight writer Ashley Person is a PhD candidate in the Cohn lab in the Vaccine and Infectious Disease Division at Fred Hutch. She studies how HIV-infected cells persist over time in people living with HIV on long term treatment.