Red Blood Cells and Cancer

Novel immunotherapy produces high rate of lymphoma remission

City of Hope has announced  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. Sixty percent had a complete response, meaning the cancer could not be detected.
 
Elizabeth Budde bio image
Elizabeth Budde, M.D., Ph.D.
“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 in City of Hope's Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, who discussed the results Dec. 11 at an American Society of Hematology annual meeting 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 followup 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 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.