SAN DIEGO – In the phase 3 Alliance A041202 trial of older patients with previously untreated chronic lymphocytic leukemia (CLL), ibrutinib showed superior progression-free survival (PFS). Results of the trial were reported by Jennifer A. Woyach, MD, of the Ohio State University in Columbus during a press briefing at the recently concluded American Society of Hematology 2018 meeting. The briefing was based on an abstract from the meeting.
“There was no difference in progression-free survival between ibrutinib and ibrutinib plus rituximab,” said Dr. Woyach. “We undertook this study to determine the most effective therapy for older patients with CLL.” She noted that the findings justify the use of ibrutinib as a standard-of-care treatment for CLL patients aged 65 years and older.
Median age of patients in the study was 71 years and 67% of the patient were men, a profile that is similar, to those of patients with CLL seen at the US Department of Veterans Affairs.
The 2-year PFS was 74% in 183 patients randomized to receive standard chemoimmunotherapy with bendamustine and rituximab (BR), compared with 87% in 182 patients randomized to receive ibrutinib alone (hazard ratio, 0.39 vs. BR), and 88% in 182 patients who received ibrutinib and rituximab (IR; HR, 0.38 vs. BR). Median PFS in this study was 43 months in the BR arm, and was not reached in either of the ibrutinib-containing arms, she said. No significant differences in overall survival (OS) were seen among the treatment arms, which may have been because of short follow-up and the fact that patients in the BR arm were allowed to cross over to ibrutinib if they progressed on treatment.
The results suggest that the additional of rituximab provided little benefit to the patients though it does add to both the costs and the chair time in an infusion center, according to former Association of VA Hematology/Oncology Mary Thomas, MS, CNS, AOCN.
“I think this really does indicate that ibrutinib as front-line therapy, which many clinicians have been doing, is a very reasonable practice,” said David P. Steensma, MD, of Dana-Farber Cancer Institute in Boston, who moderated the press briefing.
Dr. Woyach added, however, that while ibrutinib represents a major therapeutic advance, its cost and its toxicities in older patients are a concern that warrant close monitoring and development of strategies to reduce the need for long-term continuous treatment.
Thomas agreed noting that health care providers needs to be aware of the risk of atrial fib and bleeding when using ibrutinib and to ensure that patient will be able to adhere to daily dosing.
Additional phase 3 studies set to open soon will compare ibrutinib in combination with venetoclax and obinutuzumab with standard ibrutinib.
Dr. Woyach and Ms. Thomas reported having no disclosures. Dr. Steensma reported receiving research funding from, and/or serving as a consultant, board member, or adviser for Takeda Pharmaceutical, Syros Pharmaceuticals, Otsuka Pharmaceutical, Onconova Therapeutics, Novartis, Kura Oncology, Janssen, H3 Biosciences, Celgene, Amphivena Therapeutics, and Acceleron Pharma.