A new combination of three drugs that harness the body’s immune system is safe and effective, destroying most cancer cells in 95 percent of patients with recurrent Hodgkin lymphoma, according to the results of an early phase study.
Presented December 3 at the annual meeting of the American Society of Hematology in San Diego, the study in 19 men and women found that injections of ipilimumab (Yervoy®), nivolumab (Opdivo®), and brentuximab vedotin (Adcetris®) safely decreased tumor size or spread to some degree in 18 patients after at least 6 months of treatment, with 16 patients showing complete disappearance (remission) of tumors. After 9 months of treatment, 15 remained in complete remission with no sign of their cancer’s return (relapse).
Researchers say the triple therapy was generally well tolerated with relatively mild effects, such as rash, diarrhea, and nausea—issues that mostly went away when treatment stopped.
The multicenter clinical trial, led by Catherine M. Diefenbach, MD, at NYU School of Medicine and its Perlmutter Cancer Center, was conducted in patients for whom initial standard chemotherapy or stem cell transplantations failed to stop cancer cell growth. The research team says its latest results extend work reported at the same meeting in 2015 and 2016, which found that double combinations with brentuximab vedotin and nivolumab, or brentuximab vedotin and ipilimumab, were also safe and highly active against relapsed lymphoma.
The success of these efforts spurred Dr. Diefenbach and her colleagues to investigate how well other immunotherapy drug combinations performed in such hard-to-treat cases, including the current Phase I safety study.
Dr. Diefenbach, a Perlmutter Cancer Center hematologist–oncologist, says treatment options are “extremely limited” for the 3 in 10 Hodgkin lymphoma patients who fail to respond to initial therapy. The disease, she notes, affects mostly those under age 40, leading to some 1,300 deaths per year. However, most cases of Hodgkin lymphoma are considered curable if diagnosed and treated early.
“Our study results are promising and demonstrate the potential for combination immunotherapy to dramatically improve if not change the standard of care in how we treat patients whose Hodgkin lymphoma returns after initial treatment,” says Dr. Diefenbach, an assistant professor at NYU Langone and clinical director of lymphoma program services at Perlmutter.
Dr. Diefenbach says a larger Phase II clinical trial is already underway in which patients are randomly assigned to receive the triple or double combinations, allowing the scientists to demonstrate if either strategy is better than the other.
According to Dr. Diefenbach, brentuximab vedotin works by homing in on CD30, a protein on the surface of some Hodgkin lymphoma cells, and then delivering an attached dose of chemotherapy to destroy the cell. Nivolumab turns off an inhibitory switch, or checkpoint, called PD1 on T-cell surfaces, undoing the immune system’s inability to identify and attack tumor cells. Ipilimumab works very similarly to nivolumab, she says, but targets a different checkpoint, called CTLA4.
Funding support for the study, known formally as the ECOG-ACRIN Cancer Research Group, was provided by National Cancer Institute grants R01 CA180820, R01 CA180794, R01 CA180790, R01 CA180795, U10 CA180799, R01 CA180802, R01 CA180816, R01 CA180833, R01 CA180864, and R01 CA180847. Additional research support was provided to Dr. Diefenbach by American Cancer Society grant MRSG-14-052-01.
Dr. Diefenbach reports having received consulting fees and research funding from Seattle Genetics and Bristol-Myers Squibb, the manufacturers of the drugs used in this study. She has also received consulting fees and research funding from Bayer; Genentech; Incyte; LAM Therapeutics; MEI; Merck; Millennium; and Roche; and reports a financial interest in Gilead Sciences—companies involved in the production and development of several lymphoma therapies. All relationships are being managed in accordance with the policies of NYU Langone.
Besides Dr. Diefenbach, other study investigators involved in this research are Fangxin Hong, MD, at the Dana Farber Cancer Institute in Boston; Richard Ambinder, MD, PhD, at Johns Hopkins Medicine in Baltimore; Jonathan Cohen, MD, MS, at Emory University in Atlanta; Michael Robertson, MD, at Indiana University Hospital in Indianapolis; Kevin David, MD, at Rutgers Cancer Institute of New Jersey; Ranjana Advani, MD, at Stanford University in California; Timothy Fenske, MD, at the Medical College of Wisconsin in Milwaukee; Stefan Barta, MD, MS, and Yang Lui, MD, at Fox Chase Cancer Center in Philadelphia; Neil Palmisiano, MD, MS, at Thomas Jefferson University in Philadelphia; Jakub Svoboda, MD, at Penn Medicine in Philadelphia; David Morgan, MD, at Vanderbilt University in Nashville, Tennessee; Reem Karmali, MD, at Northwestern University in Chicago; Brad Kahl, MD, at Washington University in St. Louis, Missouri.; and Stephen Ansell, MD, at the Mayo Clinic in Rochester, Minnesota.