Dr Biran on Future Research Directions in Multiple Myeloma

Noa Biran, MD, associate professor, medicine, Hackensack Meridian School of Medicine, physician, Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack Meridian Health, discusses potential avenues for future research and drug development in multiple myeloma.

As the focus of multiple myeloma research continues to shift toward patients with improved long-term survival, an increasing incidence of immune deficiency, chronic infections, unusual opportunistic infections, and upper respiratory infections necessitating repeated hospitalization has been observed, Biran begins. These complications can arise from prolonged treatment and chronic steroid use, she explains. More specifically, the use of bispecific T-cell engagers (BiTEs) is known to significantly dampen both T-cell and overall immune response, Biran notes. Accordingly, the challenge for the field is to harness the efficacy of BiTEs and simultaneously mitigate these adverse effects, Biran states.

One promising approach is the identification of new cell-surface antigen targets, such as FcRH5, which has been identified as an attractive B-cell lineage-specific surface marker in multiple myeloma and can be targeted with CAR T-cell therapy, Biran says. Another strategy involves adjusting the duration and frequency of treatment with BiTEs, according to Biran. For instance, using BiTEs as a fixed-duration regimen—administered for 6 to 12 cycles before stopping treatment—might reduce the risk of long-term immune suppression, she explains. Additionally, switching to a monthly dosing regimen, which is already being evaluated in clinical trials, could further enhance safety by allowing the immune system more time to recover between doses, Biran proposes.

Overall, optimizing the sequencing and dosing of therapies to prevent infections is crucial, Biran emphasizes. The field needs to innovate and move toward safer and more conservative use of these powerful therapies by learning how to sequence and dose them more appropriately, she reiterates. In doing so, infections and immune deficiencies associated with long-term multiple myeloma management can be more effectively prevented, Biran concludes.