ASH 2021: 4 Immunotherapies Highlight Transformations in Blood Cancer Treatment

Four promising studies representing multiple approaches to bolster the immune system against blood cancer are being presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition. 

Three of the studies focus on non-Hodgkin’s lymphoma, which start in white blood cells, while one study describes a treatment for multiple myeloma, a cancer of plasma cells. 

The first study, a Phase 3 trial for multiple myeloma, showed that a three-drug standard treatment can be improved with isatuximab, a monoclonal antibody that directly fights cancer while stimulating the immune system. 

The second study, a Phase 1/2 for follicular lymphoma, involved a bispecific antibody treatment that achieved deep and lasting responses in patients with the disease. 

The third and fourth studies demonstrated how two CAR-T cell therapies for large B-cell lymphoma have the potential to be used as second-line treatments. 

Details of the four studies are summarized below.

Immune-Booster Isatuximab Beats Standard of Care for Multiple Myeloma 

The addition of anti-CD38 isatuximab to a three-drug standard of care treatment hit the primary endpoint in the Phase 3 GMMD-HD7 trial for newly-diagnosed multiple myeloma. 

In the trial, 50.1% of 662 patients receiving isatuximab with a three-part induction therapy consisting of lenalidomide, bortezomib and dexamethasone (RVd) achieved minimal residual disease negativity (no detectable cancer in the blood marrow), compared to 35.6% of those receiving RVd alone. 

Patients receiving isatuximab + RVd were more likely to respond to treatment and less likely to show disease progression. 

According to the research team, isatuximab works directly on myeloma cells and also stimulates the immune system. The Phase 3 trial will continue to investigate the antibody in patients who have just undergone autologous stem cell transplantation. 

Enduring Remissions Seen for Bispecific Antibody Mosunetuzumab in Follicular Lymphoma 

A Phase 1/2 trial investigated mosunetuzumb in patients with relapsed/refractory follicular lymphoma who have received two or more lines of therapy met its primary endpoint. 

In patients receiving intravenous mosunetuzumab, 60% achieved complete response while response is seen in 80%. Over 60% of patients who responded and 76% of those who had a complete response had no complications or cancer progression a year after treatment. 

Developed by Roche’s Genentech, mosunetuzumab targets CD20 on lymphoma cells and CD3 on T cells. It helps guide T cells to lymphoma cells. When T cells get close, they are activated to kill the cancer cell. 

Cytokine release syndrome (CRS), an inflammatory response common in immune-modulating therapies, occurred in 44.4% of patients, but all cases were manageable, resulting in no hospitalizations. 

Mosunetuzumab could offer an alternative to chemotherapy for follicular lymphoma, said a researcher. 

CAR-T Cell Therapy Liso-cel Outperforms Chemo for Hard-to-Treat Large B-Cell Lymphoma 

An interim analysis of the Transform trial comparing CAR-T cell therapy lisocabtagene maraleucel (liso-cel) to standard of care (salvage chemotherapy followed by autologous stem cell transplantation) showed that liso-cel significantly improved event-free survival for patients with large B-cell lymphoma. 

Patients receiving liso-cel survived a median 10.1 months without complications or cancer progression. That was 7.8 months longer than those receiving the standard of care treatment, who lasted a median of 2.3 months. 

Liso-cel also improved complete response rates; 66% of patients receiving liso-cel achieved complete response compared to 39% of those in the standard of care group. 

Side effects of liso-cel included CRS and neurotoxicity, but were manageable and comparable to standard of care. 

The trial will continue to assess differences in overall survival. 

CAR-T Cell Therapy Axi-cel Improves Survival in Large B-Cell Lymphoma 

A primary analysis of the two-year data from the Zuma-7 trial comparing CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with standard of care in patients with aggressive large B-cell lymphoma, showed that axi-cel significantly improved progression-free survival (PFS), which met the trial’s primary endpoint. 

83% of the patients receiving axi-cel showed a response to treatment, compared to 50% of those receiving standard of care. Patients receiving axi-cel also survived a median of 8.3 months without additional cancer treatment or cancer progression, compared to two months in the standard of care group. 

Rates of adverse events were similar in both arms (91% in the axi-cel arm and 83% in the standard of care arm), and were similar to previous trials. Common side effects of axi-cel included low blood cell counts, CRS and neurotoxicity. 

Researchers are advocating for the use of CAR-T cell therapy in earlier lines of lymphoma treatment, to reduce the amount of chemotherapy the patients are exposed to.

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ASH2020: New Studies Showcase Potential of CAR-T Therapy to Treat More Cancers Roche Impresses with its Bispecific Antibody Portfolio for Blood Cancer Treatments New Frontiers in Therapeutics Xencor and Janssen Join Forces Against B-cell Lymphoma in a New Billion-Dollar Deal

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Joy Lin

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