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Pivotal Study Led by City of Hope Shows First-in-Class Cancer Immunotherapy Achieves High Rate of Remission in Patients With a Type of Non-Hodgkin Lymphoma

Data on bispecific antibody for a non-Hodgkin lymphoma presented today at an American Society of Hematology (ASH) Annual Meeting press briefing

City of Hope announced today that data from an investigational Phase 1/2, single arm trial using a bispecific antibody called mosunetuzumab highlights the paradigm-changing potential of a new treatment option for people with follicular lymphoma, a type of blood cancer and the most common indolent form of non-Hodgkin lymphoma (NHL). Patients within the trial achieved high response rates with 80% of patients responding positively to the treatment, and 60% had a complete response, meaning the cancer could not be detected.

“Our study demonstrated that an antibody based on bispecific T cell engaging technology is proving to work very well with high response rates — and safely — in blood cancer patients who need more effective therapies and with fewer side effects,” said Elizabeth Budde, M.D., Ph.D., associate professor, City of Hope Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, who discussed the results today at an ASH press briefing. “Mosunetuzumab is a very promising therapy, showing deep and durable responses for patients whose lymphoma has relapsed or is no longer responding to currently available therapies.”

Instead of concentrating on a singular target, “bispecific” antibodies are therapeutics that act on two cellular targets simultaneously. In the case of mosunetuzumab, one “arm” targets the CD3 protein on T cells, an immune cell that can help in the fight against cancer if engaged; a second “arm” binds to CD20, a protein commonly found on lymphoma cells.

“The two cell groups are pulled together, with mosunetuzumab serving as a kind of bridge,” Budde said. “Being in such close proximity allows the now activated T cells to better recognize and attack the lymphoma cells.”

Ninety patients with follicular lymphoma, who ranged in age from 29 to 90 years old, were enrolled in the multicenter international trial. The patients received mosunetuzmab, a Genentech medicine, intravenously every 21 days for a minimum of eight cycles and up to 17 cycles.

The median time to first response was 1.4 months. With a median follow up of 17.8 months, 70% patients with response continued to do well.

Cytokine release syndrome was a side effect in 44% of patients. Most were low grade and occurred during the first cycle. All resolved completely. Other side effects included fatigue and headache. Only two patients discontinued treatment due to mosunetuzumab-related side effects.

Genentech, a member of the Roche Group, plans to submit this new data to the U.S. Food and Drug Administration in the near future for approval consideration. If approved, mosunetuzumab has the potential to be the first CD20xCD3 T cell engaging bispecific antibody approved for NHL.

Renee Bentson, 69, of Covina, California, was one of the first participants in the trial at City of Hope. Before she was diagnosed with cancer, Bentson, who was physically active and running seven miles a day, began to notice a rash, chest pain and night sweats. When an unusual fatigue set in and lumps began to appear, first on one side of her torso, then the other and on one arm, Bentson consulted a doctor, who promptly ordered a biopsy.

Bentson was diagnosed with follicular lymphoma, which makes up about 20% of all lymphoma cases. It tends to strike older people, and though it does respond to initial treatment, it is not curable with convention therapy and relapse is frequent. Remission duration tends to get shorter with each subsequent relapse after treatment.

While some patients do well on chemotherapy, Bentson was concerned about the potential side effects. She participated in a series of immunotherapy clinical trials. The cancer would shrink, but not disappear, and later it would recur. With mosunetuzumab, which was her fourth line of treatment, the cancer went into remission in early 2017 and she has been cancer free since then.

“I’m just so grateful that it worked,” said Bentson, who experienced few side effects from the treatment.

City of Hope is a leader in blood cancer immunotherapies. The National Cancer Institute-designated comprehensive cancer center has performed more than 17,000 bone marrow/stem cell transplants and is a leader in chimeric antigen receptor (CAR) T therapy, with nearly 800 patients treated with immune effector cells, including CAR T therapy, and nearly 80 open or completed trials.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nation’s “Best Hospitals” in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. Translational Genomics Research Institute (TGen) became a part of City of Hope in 2016. AccessHopeTM, a subsidiary launched in 2019, serves employers and their health care partners by providing access to NCI-designated cancer center expertise. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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Photography by Christophe Tomatis
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