News Tips From NYU School Of Medicine And Perlmutter Cancer Center Researchers At The 60th American Society Of Hematology Meeting, Dec. 1-4, In San Diego, Calif.

Studies Suggest that Immunotherapy Adds Punch to Earlier Attempts to Treat Recurrent Non-Hodgkin and Hodgkin Lymphoma

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Dec 03, 2018, 13:30 ET

NEW YORK, Dec. 3, 2018 /PRNewswire/ -- New drugs that harness the body's immune system to destroy cancer cells appear to increase the effectiveness of later drug therapies for non-Hodgkin and Hodgkin lymphoma patients, new research suggests. This happens, scientists say, even for repeat drug therapies whose initial attempts failed to stop or reverse the disease.

Researchers at NYU School of Medicine and its Perlmutter Cancer Center who led the pair of new studies, both presented Dec. 1 at the annual meeting of the American Society of Hematology in San Diego, say their findings are the first multicenter data to show that even when "second-line" immunotherapy fails to control the disease, it likely "sensitizes" lymphoma patients to better respond to future use of drugs that did not work very well the first time. Few treatment options exist, researchers say, for relapsing non-Hodgkin lymphoma patients.

Both studies involved a review of the medical records of men and women treated between 2012 and 2018 at 17 medical centers in the United States and Canada, all of whom failed to have a lasting response to initial therapy, including stem cell transplantations and/or standard chemotherapy with or without brentuximab vedotin (marketed as Adcentris), a drug that primes the immune system and aids chemotherapy. Subsequent therapy with so-called checkpoint-blockade inhibitors, such as ipilimumab (Yervoy) and nivolumab (Opdivo), were also not successful in controlling cancer spread. When effective, such drugs work by turning off inhibitory switches, or "checkpoints," on immune T cell surfaces, which are known to prevent the immune system from identifying and attacking tumor cells.

However, in 59 patients with non-Hodgkin lymphoma, 30 responded to additional chemotherapy or other drug treatment after having received checkpoint inhibitors. Of the 29 patients still alive and receiving therapy, 16 have not seen any cancer spread.

In 112 patients with Hodgkin lymphoma who received checkpoint blockade therapy, 81 needed some form of follow-up drug treatment. Sixty-six remain alive, and 30 have not experienced any worsening of their disease.

"These are very high success rates for post-checkpoint blockade therapy, especially in patients for whom several drug therapies have failed, including the same or similar drugs used again after checkpoint therapy," says senior study investigator and hematologist-oncologist Catherine Diefenbach, MD.

Diefenbach, an assistant professor at NYU Langone and clinical director of lymphoma program services at its Perlmutter Cancer Center, cautioned that prospective clinical trials, in which patients are closely monitored from the start of their therapy over long periods of time, are needed before researchers can conclude whether or not checkpoint blockade therapy was responsible for the greater effectiveness of subsequent treatments.

"What our current study strongly suggests, however, is that the benefits of checkpoint blockade therapy are not limited to their initial ability to stop the disease," says lead study investigator Nicole Carreau, MD, a postdoctoral hematology and oncology fellow at NYU Langone and Perlmutter.

Both kinds of lymphoma are cancers of immune cells that help the body fight off infections and other diseases, says Carreau. Non-Hodgkin lymphoma is more common in the United States, with more than 72,000 new cases diagnosed each year (with more than 20,000 deaths from the disease), compared with about 8,500 for Hodgkin lymphoma (and over 1,000 deaths).

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 Diefenbach by American Cancer Society grant MRSG-14-052-01.

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 Diefenbach and Carreau, other NYU Langone researchers involved in this study are Andrea Troxell, ScD; Orrin Pail, MD; and Yuhe Xia, MS. Additional study investigators are Philippe Armand, MD, and Reid Merryman, MD, at Dana-Farber Cancer Institute in Boston; Ranjana Advani, MD, and Michael Spinner, MD, at Stanford University in California; Alex Herrera, MD, Robert Chen, MD, and Sarah Tomassetti, MD, at City of Hope National Medical Center in Duarte, Calif.; Radhakrishnan Ramchandren, MD, and Muhammad Hamid, MD, at Wayne State University in Detroit; Sarit Assouline, MD, and Raoul Santiago, MD, at McGill University in Montreal; Nina Wagner-Johnston, MD, and Suman Paul, MD, PhD, at Johns Hopkins Medicine in Baltimore; Jakub Svoboda, MD, and Steven Bair, MD, at Penn Medicine in Philadelphia; Stefan Barta, MD, MS, and Yang Lui, MD, at Fox Chase Cancer Center in Philadelphia; James Godgrey, MD, at University of Chicago; Sunita Nathan, MD, and Reem Karmali, MD, at Rush University in Chicago; Madelyn Burkhart, MD, at Northwestern University in Chicago; Pallawi Torka, MD, at Rosswell Park Cancer Center in Buffalo, NY; Kevin David, MD, and Catherine Wei, MD, at Rutgers Cancer Institute of New Jersey in New Brunswick; Frederick Lansigan, MD, at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire; David Persky, MD, at the University of Arizona in Tucson; Sonali Smith, MD, at University of Chicago Medicine; and Julio Chavez, MD, at the Moffitt Cancer Center in Tampa.

Note: This presentation, Abstract #679, is titled A Phase I Study with an Expansion Cohort of the Combination of Ipilimumab, Nivolumab, and Brentuximab Vedotin in Patients with Relapsed/Refractory Hodgkin Lymphoma: a Trial of the ECOG-ACRIN Cancer Research Group (R4412 Arms G to I). The study will be presented in Room 6F at the San Diego Convention Center in California.

Combination Immunotherapy Shows High Activity Against Recurrent Hodgkin Lymphoma

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 Dec. 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 (marketed as Yervoy), nivolumab (Opdivo), and brentuximab vedotin (Adcentris) safely decreased tumor size or spread to some degree in 18 patients after at least six months of treatment, with 16 patients showing complete disappearance (remission) of tumors. After nine 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 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 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.

Diefenbach, a Perlmutter hematologist-oncologist, says treatment options are "extremely limited" for the three 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 Diefenbach, an assistant professor at NYU Langone and clinical director of lymphoma program services at Perlmutter.

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 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 PD1on 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.

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 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, Tenn.; Reem Karmali, MD, at Northwestern University in Chicago; Brad Kahl, MD, at Washington University in St. Louis, Mo.; and Stephen Ansell, MD, at the Mayo Clinic in Rochester, Minn.

Note: These presentations are abstracts #93 and #1626. Abstract #93 is titled Checkpoint Blockade Therapy May Sensitize Aggressive and Indolent Non-Hodgkin Lymphoma to Subsequent Therapy. The study will be presented in the Pacific Ballroom at the Marriott Marquis San Diego in California, at 1 pm EST. Abstract #1626 is titled Checkpoint Blockade Therapy May Sensitize Hodgkin Lymphoma to Subsequent Therapy. The poster will be presented in Hall GH at the San Diego Convention Center at 9:15 pm EST.

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SOURCE NYU Langone Health