Do Risks Outweigh Benefits for Use of Idelalisib Plus Ofatumumab in CLL?
Posted: Thursday, August 1, 2019
Although the combination of the PI3K blocker idelalisib and the anti-CD20 antibody ofatumumab produced responses in the first-line treatment of chronic lymphocytic leukemia (CLL), it seems to have an unacceptable safety profile. Benjamin L. Lampson, MD, of the Dana-Farber Cancer Institute and Harvard School of Medicine, and colleagues reported the results of this single-arm, open-label, nonrandomized phase II trial in Blood Advances.
“Future investigative efforts must identify ways of effectively blocking this pathway while simultaneously mitigating toxicities,” concluded the authors.
A total of 27 patients with treatment-naive CLL were included in the trial and received treatment. Of them, 5 patients had TP53-aberrant disease, 3 patients had an 11q deletion, and 13 patients had unmutated immunoglobin heavy-chain variable region. Patients received idelalisib for 2 monthly cycles, followed by idelalisib plus ofatumumab for 6 cycles, then idelalisib indefinitely.
The median time of therapy for all patients was 8.1 months, and the median time for patients who discontinued treatment was 7.7 months. The median follow-up was 39.7 months. The median progression-free survival was 23 months, and the overall response rate was 88.9%, including 21 patients with a partial response and 1 with a complete response.
In terms of safety, more than half of patients (57%) prematurely discontinued treatment as a result of toxicity. The most frequent grade 3 or greater adverse events included transaminitis (52% of patients), neutropenia (33%), colitis/diarrhea (15%), and pneumonitis (7%). Several patients acquired opportunistic infections including but not limited to Pneumocystis jirovecii, Aspergillus, and herpes simplex virus.
Disclosure: The study authors’ disclosure information may be found at bloodadvances.org.
