Dr Zonder on Unmet Needs to be Addressed in Multiple Myeloma

Jeffrey Zonder, MD, leader, Multiple Myeloma and Amyloidosis Multidisciplinary Team, Barbara Ann Karmanos Cancer Institute; professor, medicine, Departments of Hematology and Oncology, Wayne State University School of Medicine; member, Leukemia & Lymphoma Society – Michigan Chapter, discusses notable unmet needs that remain to be addressed in the treatment of patients with relapsed/refractory multiple myeloma.

Zonder begins by stating that he believes there are 2 areas that represent significant unmet needs for this patient population. One area, which was not thoroughly addressed at the 2023 ASH Annual Meeting but holds considerable importance, pertains to ongoing studies regarding the role of maintenance therapy with daratumumab (Darzalex) or multiple drugs in patients initially treated with quadruplet therapy, he explains. The question then arises of whether treatment with an anti-CD38 antibody should be continued throughout the course of treatment, he asks. The benefit of continuing treatment with an anti-CD38 antibody vs pausing this treatment and continuing it later is unknown, according to Zonder. Studies evaluating these questions have been formulated and patient enrollment has commenced, yet oncologists await the outcomes of these trials, he continues. Realistically, 1 or 2 more years may pass before insight is gained from these investigations, Zonder notes.

Another notable unmet need, which garnered significant attention at both the 2023 ASH Annual Meeting and the International Myeloma Society Annual Meeting, revolves around the optimal use of CAR T-celltherapies and bispecific antibodies in patients with multiple myeloma, particularly when both treatment modalities are available, he says. Many of these therapies target the same antigen on myeloma cells: BCMA. However, with the FDA approval of the bispecific antibody talquetamab (Talvey), which doesn't target BCMA, and the development of CAR T-cell therapies targeting different antigens, questions arise regarding optimal treatment sequencing and target pursuit in patients with relapsed/refractory disease, Zonder explains.

Additionally, there's a need to address the management of on-target/off-tumor adverse effects associated with talquetamab. The immunotherapy paradigm for multiple myeloma is complex and requires careful dissection, making it one of the focal points at the 2023 ASH Annual Meeting, especially within the relapsed setting, where abstracts on specific therapies and CAR T-cell products predominated, he concludes.