Madhav V. Dhodapkar, MBBS
“BCMA-targeting bispecific antibodies work, showing impressive single-agent activity in heavily pretreated multiple myeloma. This class of agents is likely to become an important component of future antimyeloma therapies, but we must learn how to optimally use them,” said Madhav V. Dhodapkar, MBBS, Professor and Anise McDaniel Brock Chair, Department of Hematology and Medical Oncology, and Director of the Center for Cancer Immunology, Emory University, Atlanta.
At the ASCO meeting, Dr. Dhodapkar was invited to discuss MajesTEC-11 and the phase II MagnetisMM-2 trial of another BCMA [B-cell maturation antigen]-targeting bispecific elranatamab,2 which reported response rates of 63.0% and 60.6%, respectively. “We’re seeing deep and durable responses and activity in cytogenetically high-risk disease, without question,” he said.
‘A Two-Edged Sword’
However, BCMA-targeting bispecific antibodies may well be “a two-edged sword” in myeloma, according to Dr. Dhodapkar. Aside from their ability to shrink tumors, they are also associated with early toxicities (cytokine-release syndrome and immune effector cell–associated neurotoxicity) and possibly longer-term ones. Of note, perhaps because of chronic T-cell activity and on-target plasma cell depletion, patients appear to be at increased risk for infections, viral reactivation, and inadequate response to vaccines. In the clinical trials, Pneumocystis jirovecii and cytomegalovirus reactivation have emerged, and several COVID-19–related deaths have been reported.
“What we are learning is that infections are appearing as major adverse events in this population…, and there is a distinct pattern of infection that has begun to emerge,” he noted.
Dr. Dhodapkar said that with bispecific antibodies, there is a “complex interaction between tumor-associated and host-dependent factors,” which affect alterations in the immune system. They, in turn, influence a patient’s ability to deal with pathogens, viral reactivation, and pandemics. We do need to learn how to use these new therapies more safely and pay attention to the risk of infections.
“The goal of immunotherapy is to maximize durable tumor immunity in the context of tumor and host biology and minimize the risk of threats,” stated Dr. Dhodapkar. “T-cell redirection may be associated with an increased risk of infections, which should be recognized and managed. It would be important to better understand which patients are at highest risk of these complications, and then either consider limiting therapy or use prophylactics.”
DISCLOSURE: Dr. Dhodapkar has served as a consultant or advisor to Janssen Oncology, Lava Therapeutics, and Roche/Genentech.
1. Nooka AK, Moreau P, Usmani SZ, et al: Teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: Updated efficacy and safety results from MajesTEC-1. 2022 ASCO Annual Meeting. Abstract 8007. Presented June 5, 2022.
2. Lesokhin AM, Arnulf B, Niesvizky R, et al: Initial safety results for MagnetisMM-3: A phase 2 trial of elranatamab, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. 2022 ASCO Annual Meeting. Abstract 8006. Presented June 5, 2022.
In patients with multiple myeloma exposed or refractory to three standard therapies, treatment with the bispecific antibody teclistamab produced strong and durable responses in the phase I/II MajesTEC-1 study.1 The results of weekly subcutaneous dosing of teclistamab in 165 patients were presented...