image: Nitin Jain, M.D. view more
Credit: MD Anderson Cancer Center
Ibrutinib and venetoclax, two FDA-approved drugs for treating chronic lymphocytic leukemia (CLL), have been shown to be effective when given together for high-risk and older patients with the disease, according to a study at The University of Texas MD Anderson Cancer Center.
Study findings were published in the May 29 online issue of the New England Journal of Medicine. Lead researchers included Nitin Jain, M.D., associate professor of Leukemia, William Wierda, M.D., Ph.D., professor of Leukemia; and Varsha Gandhi, Ph.D., department chair ad interim of Experimental Therapeutics.
Researchers followed 80 previously untreated patients in a Phase II study. Median age was 65 years with 30 percent over age 70. Ninety-two percent had high-risk genetic anomalies. Eighty-eight percent of patients had complete remission with normal or incomplete blood count recovery after 12 cycles of treatment. Sixty-one percent of patients had complete remission with undetectable minimal residual disease.
"These efficacy results are substantially better than what has been reported with ibrutinib or venetoclax monotherapy for CLL patients," said Jain "With monotherapy, the majority of responses have been partial, and remissions with undetectable minimal residual disease in bone marrow has been rare."
Jain added that more robust therapies are needed for patients with CLL given that the majority of patients are older than 65 and existing therapies are not always effective.
"This group of patients often has unacceptable side effects and has a lower rate of complete remission and undetectable minimal residual disease," said Jain. "Our data showed that non-chemotherapy, combination therapy with ibrutinib and venetoclax demonstrated no new toxic effects compared to what has been previously reported for the individual agents."
The study reported that 60 percent of patients developed low white blood cell counts, which was similar to what has been reported in other venetoclax combination trials. No new safety concerns were observed with the combination therapy.
While the current median follow-up of the trial is 14.8 months, Jain said that "a longer follow-up is needed to adequately assess the long-term safety of this combination."
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Study team participants included: Michael Keating, M.D.; Philip Thompson, M.D.; Alessandra Ferrajoli, M.D.; Jan Burger, M.D., Ph.D.; Gautam Borthakur, M.D.; Koichi Takahashi, M.D.; Zeev Estrov, M.D.; Tapan Kadia, M.D.; Marina Konopleva, M.D., Ph.D.; Yesid Alvarado, M.D.; Musa Yilmaz, M.D.; Courtney DiNardo, M.D.; Prithviraj Bose, M.D.; Maro Ohanian, D.O.; Naveen Pemmaraju, M.D.; Elias Jabbour, M.D.; Koji Sasaki, M.D.; Katrina Sondermann; Nichole Cruz; Chongjuan Wei, Ph.D.; Ana Ayala; and Hagop Kantarjian, M.D.; all of the Department of Leukemia; Nathan Flower, M.D., of the Department of Lymphoma and Myeloma; Rashmi Kanagal-Shamanna, M.D.; Keyur Patel, M.D., Ph.D.; and Jeffrey Jorgensen, M.D., Ph.D.; of the Department of Hematopathology; Xuemei Wang, of the Department of Biostatistics; Naveen Garg, M.D., of the Department of Diagnostic Radiology; and William Plunkett, Ph.D., of the Department of Experimental Therapeutics.
The study was funded by AbbVie Inc.; the Andrew Sabin Family Foundation; the CLL Global Research Foundation; and the National Institutes of Health (P30 CA016672). The study also was supported with funding from the Chronic Lymphocytic Leukemia Moon Shot™, part of MD Anderson's Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients' lives. Jain, Wierda and Gandhi received grant funding from AbbVie, and Jain has received honoraria from and has served on the Advisory Board for AbbVie.
Journal
New England Journal of Medicine