Dr Banerjee on the Impact of Dose Modification Studies in Multiple Myeloma

Rahul Banerjee, MD, FACP, assistant professor, Clinical Research Division, Fred Hutch Cancer Center; member, the International Myeloma Working Group; assistant professor, Division of Hematology and Oncology, University of Washington, discusses the clinical impact of dose modification studies on the treatment of patients with multiple myeloma.

One of the most practice-changing studies in 2023 came from an extension of the phase 2 MonumenTAL-1 trial (NCT04634552), Banerjee begins. Data from this study were shared at the 2023 ASH Annual Meeting and presented by Ajai Chari, MD, of the University of California, San Francisco, he details. This study examined dose modifications for talquetamab-tgvs (Talvey), including reducing the dosing frequency from every 2 weeks to every 4 weeks or halving the dose and maintaining the 2-week dosing schedule, he explains. The findings revealed that many toxicities associated with talquetamab, including dysgeusia, improved with these adjusted dosing regimens, Banerjee reports.

GPRC5D, the unique protein targeted by talquetamab, is present on myeloma cells, as well as tongue, skin, and nail cells—forming an unusual grouping of epithelial and plasma cell lineage, he continues. Banerjee adds that talquetamab has shown robust efficacy, even in patients who have previously received BCMA-directed therapies. However, dysgeusia affects a similar proportion of patients, leading to significant weight loss in some cases, Banerjee states. He notes that many of his patients experience alterations in taste and develop nail or skin issues during treatment with talquetamab. Although they are able to achieve remission with this therapy, managing associated toxicities can be challenging, he notes

This study showed that dose de-escalation of talquetamab led to improvement in most toxicities, although weight loss remains a concern, Banerjee continues. This is a significant shift to treatment approaches within the myeloma field, which has long focused on administering the maximum tolerated dose of a given therapy, he explains. Banerjee says that it is encouraging to see early efforts to optimize dosing for bispecific antibodies like talquetamab. This approach may improve safety profiles, particularly minimizing infection risks and mitigating GPRC5D-related adverse effects, Banerjee concludes.