Dr Jagannath on the Patient Population in the LINKER-MM1 Trial in Multiple Myeloma

Sundar Jagannath, MBBS, director, Center of Excellence for Multiple Myeloma, professor, medicine (hematology and medical oncology), The Tisch Cancer Institute, Mount Sinai, discusses the patient population evaluated in the phase 1/2 LINKER-MM1 trial (NCT03761108) of linvoseltamab (REGN5458) in relapsed/refractory multiple myeloma.

The patient characteristics of those enrolled in the LINKER-MM1 trial reveal a cohort that mirrors the demographic diversity and disease severity often encountered in real-world multiple myeloma populations, Jagannath begins. A total of 117 patients received the 200 mg dose of linvoseltamab across the phase 1 and phase 2 portions of the study. Additionally, 17.1% of the patients identified as African American, indicating a patient representation that aligns with the broader United States population, a factor significant for assessing external validity in clinical trials, he reports.

A notable inclusion criterion was the prerequisite for patients to have undergone at least 3 prior lines of therapy, including exposure to an immunomodulatory drug, a proteasome inhibitor, and daratumumab (Darzalex), Jagannath explains, saying that such requirements highlight the advanced disease state of the enrolled population. Moreover, the study design specifically allowed for inclusion of patients who were double refractory in the phase 1 portion and expanded to those who were triple-class refractory in phase 2, he notes.

The severity of disease burden was further evidenced by other clinical characteristics. Many patients had bone marrow infiltration exceeding 50% by plasma cells, indicating extensive myeloma involvement. The median soluble BCMA level, a marker correlating with tumor burden, was notably elevated at 368.0 ng/mL, with a broad range spanning from 18.7 ng/mL to 4430.0 ng/mL across patients, Jagannath expands. This collectively points to a population burdened by high tumor activity, a key consideration for understanding treatment response and outcomes, according to Jagannath.

Incorporation of patients with extramedullary disease, confirmed through independent review committee adjudication, further highlights the comprehensive spectrum of disease manifestations within the study cohort, he continues. The inclusion of diverse patient profiles aligns with the external validity criteria essential for regulatory evaluations, particularly for potential FDA assessments, Jagannath says. The study's ability to reflect the real-world patient population lends credence to the potential generalizability of findings to broader patient populations, Jagannath concludes.