Kenneth C. Anderson, MD
Kenneth C. Anderson, MD, Program Director, Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at Dana-Farber Cancer Institute, and Kraft Family Professor of Medicine, Harvard Medical School, was upbeat about the REGN5459 study and the field of melanoma studies in general: “There has been much progress in myeloma, with 16 different classes of drugs and 31 different approvals using these agents. In many cases, we have moved myeloma to a chronic illness,” he said.
“The field of bispecific antibodies is new and exciting,” he continued. “The bispecific antibody teclistamab has been recently approved for patients with myeloma who have had four or more lines of prior therapy. Response rate was 63%, progression-free survival was 11 months, and 76% of patients developed infections. This drug is given continuously until remission is achieved,” he explained.
Principal Challenge
Newer studies are looking at the bispecific antibodies in combination. “The good news is that in combination, the response rate goes to 93%, but the frequency of cytokine-release syndrome remains high, and infections are reported in 90% [grade 3 in 37%],” he said. “These agents are exciting, but we need to learn how to use them with less cytokine-release syndrome.”
“Although Regeneron varied the degree of binding of the tumor to the effector T cell in REGN5459, there are no major differences between the outcomes in this study and the higher-affinity binding bispecific antibody REGN5458 reported earlier at this meeting,” he said.
“Responses to the normal-affinity binder and the reduced-affinity binder were both remarkable at the recommended phase II doses, with significant durations of response. No major change in the incidence of cytokine-release syndrome was reported with the low-affinity binder, but it did reduce the severity of cytokine-release syndrome. Infections remain a problem with both the low-affinity binder and the normal-affinity binder. We need to learn how to decrease infections,” Dr. Anderson stated.
“We also need to explore mechanisms of resistance and decide when and how long to treat patients with these T-cell engagers,” he added.
Looking Ahead
The field of research is rife with studies of even newer approaches that will improve the killing of myeloma cells, including a trispecific T-cell engager and drugs aimed at exploiting natural killer cells.
“We need to figure out how to reduce toxicity, and then we will be able to use these agents as outpatient treatment. In the future, bispecific T-cell engagers and [chimeric antigen receptor T-cell therapy] will be incorporated into the initial treatment of multiple myeloma to achieve durable remission. Progress continues, and the most recent example is bispecific T-cell engagers,” he told the audience.
“Some years ago, my first autologous transplant patient wrote a book about it. She said she would know she was cured when she grew old and died of something else. This is already occurring, and it is happening more frequently. The best is yet to come,” he concluded.
DISCLOSURE: Dr. Anderson reported financial relationships with OncoPep, C4 Therapeutics, Mana Therapeutics, Raqia Therapeutics, NextRNA Therapeutics, Starton Therapeutics, and Window Therapeutics; has received consulting fees from Acetylon Pharmaceuticals, Bristol Myers Squibb, Celgene, Gilead Sciences, Janssen, Precision Biosciences, Sanofi-Aventis, Takeda, and Tolero; and is on the board of directors and has stock options for OncoPep.
