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New medicine may be able to treat multiple myeloma: Study

by Pragati Singh

A recent research found that the novel medication modakafusp alf offers early promise in treating the bone marrow malignancy multiple myeloma. At the 2022 American Society of Hematology (ASH) Annual Meeting, researchers from the University of Pennsylvania’s Abramson Cancer Center reported their result (Abstract 565). 43 percent of patients who received 1.5 mg of modakafusp every four weeks as part of a Phase I/II multicenter study (NCT03215030) saw a partial response or a more than 50% decline in their malignancy. Participants in the trial had at least three prior lines of therapy, and after the preceding therapy, their illness had relapsed or stopped responding.

“We are excited by these findings and continue to be optimistic about the potential this treatment holds for patients with multiple myeloma,” said presenting author Dan Vogl, MD, an expert in blood cancers, medical director of the Clinical Research Unit at Penn Medicine’s Abramson Cancer Center, and an associate professor of Hematology-Oncology at the Perelman School of Medicine of the University of Pennsylvania. “We have been working with this new medication at Penn since we gave it to the first patient ever to receive it five years ago. We now see that a substantial number of patients benefit from modakafusp as a single agent, including patients whose myeloma has become resistant to other treatments, which is really impressive.”

A fusion protein called modakafusp (created by Takeda Pharmaceuticals) directs interferon, a pro-inflammatory hormone also used to treat various malignancies and viral infections, to cells that express CD38, a surface marker seen on myeloma cells and a number of immune cells.

In the United States, there are anticipated to be 12,640 fatalities from multiple myeloma in 2022, according to the American Cancer Society. Less than 1% of the population gets the cancer, making it rare. Despite medical advancements, myeloma is presently incurable, and all patients experience malignant relapses following first chemotherapy and other initial lines of therapy.

In this study, modakafusp showed promise in patients for whom other treatments targeting the same target, such as well-known monoclonal antibodies like daratumumab and isatuximab, had lost their efficacy. The study’s preliminary findings were presented at the ASH Annual Meeting in 2021. The medicine has tolerable side effects and induces potent anti-myeloma responses, according to the final safety and effectiveness studies released this year.

“Modakafusp has a truly novel mechanism of action, delivering a hormonal signal directly to target cells that simultaneously is toxic to cancer cells while stimulating an immune response. We saw responses in patients whose cancer did not respond to or who experienced a relapse after receiving the anti-CD38 antibody drugs that are currently on the market,” Vogl said. “We also saw responses in patients whose myeloma had developed resistance to all currently available effective therapies.”

As would be expected in a group that has had so many previous treatments, the majority of research participants (87%) had adverse events linked to their treatment. Neutropenia, or a reduction in white blood cells, and thrombocytopenia, or a low blood platelet count, were the most frequent adverse effects among research participants; around one-third of patients experienced moderate responses after receiving the medicine by infusion.

In order to determine the ideal dose of modakafusp and learn more about its efficacy in treating myeloma, Vogl and his colleagues are currently recruiting patients in a randomised phase II research.

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