Immunotherapy a ‘significant improvement’ for treatment of multiple myeloma
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Despite being behind the curve for adoption of immunotherapy, the field of multiple myeloma has witnessed monumental advances in patient survival with the use of novel agents, according to a speaker at Chemotherapy Foundation Symposium.
The need for novel immunotherapies is becoming more urgent for patients with multiple myeloma because of the significant progress in treating the disease, Faith E. Davies, MBBCh, MRCP, MD, FRCPath, director of the myeloma clinical program and Center for Blood Cancers at Perlmutter Cancer Center and professor at NYU Grossman School of Medicine, told the audience.
Improvements in survival have been accompanied by patients becoming resistant to the “main pillars of therapy,” she noted, including immunomodulatory drugs, monoclonal antibodies and proteasome inhibitors.
"We have created a new problem,” Davies said. “Patients with triple-class refractory multiple myeloma represent an emerging challenge.”
Previous studies have shown poor outcomes for patients with triple-class refractory disease after receiving the three pillars of therapy, with approximate median OS of 9 to 10 months and median PFS between 4 and 5 months, she noted. Meanwhile, response rates for subsequent lines of therapy range from 30% to 40%.
The emergence of daratumumab (Darzalex, Janssen Biotech) and isatuximab (Sarclisa, Sanofi) — both CD38-directed monoclonal antibodies — has had a huge impact on the treatment landscape for multiple myeloma, Davies said.
Additional successful therapies with novel targets have emerged, such as commercially available B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cells and investigational therapies targeting GPRC5D and FcRH5. All are notable for their extremely high response rates and seemingly durable responses, she added.
Clinical trials of investigational bispecific antibodies have shown “incredible response rates” in patients with triple-class refractory disease, Davies said. Previous classes of drugs for multiple myeloma had response rates between 30% and 40% among heavily pretreated patients, but this class of drugs has nearly doubled the response rate and responses have proved to be very durable, she said.
“These are off-the-shelf products with the potential to overcome the limitations of the immunosuppressive tumor microenvironment by redirecting T cells to kill tumor target cells,” Davies said.
The FDA recently approved teclistamab-cqyv (Tecvayli, Janssen Biotech) — a BCMA-targeted therapy — as the first bispecific antibody for the treatment of multiple myeloma. The approval applies to adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
The agent works via a T-cell redirecting bispecific antibody that binds to CD3 on T cells and BCMA on the surface of plasma cells.
Davies spoke enthusiastically about the trial results, which demonstrated “impressive response rates.” These include a 39% complete remission rate, with more than a quarter of patients in the study found to be minimal residual disease-negative after therapy.
"Importantly, for those patients who responded, the duration of response was 18 months and median PFS was 11 months,” Davies said. “This is a significant improvement over previous therapies.”
Other bispecifics are currently in development, Davies noted, including those targeting GPRC5D and FcRH5. Initial clinical results show incredibly high response rates, she added.
“There is some compelling data to suggest that one bispecific can be used and then followed by another bispecific against a different target,” Davies said. "We are really moving the goal posts here and offering patients [better] treatment options."
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Davies FE, et al. New therapeutic agents for relapsed/refractory multiple myeloma: CAR T and bispecific antibodies. Presented at: 40th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 9-11, 2022.
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