Sequential Combination Therapy for Chronic Lymphocytic Leukemia
Posted: Thursday, March 26, 2020
A two-phase treatment of bendamustine for debulking followed by ofatumumab and ibrutinib for maintenance was reported to be tolerated by a group of patients with chronic lymphocytic leukemia (CLL), with an overall response rate of 92%, according to a new phase II study. Paula Cramer, MD, of the University of Cologne in Germany, published the report with colleagues in Haematologica.
“Except for two fatal adverse events, the toxicities were generally manageable: only six patients discontinued treatment prematurely due to toxicity,” the authors wrote. “However, ibrutinib should still be used as a single agent outside clinical trials.”
The phase II multicenter study enrolled 66 patients with CLL. One patient was excluded from the efficacy analysis but was included in the safety analysis. Of the remaining 65 patients, 39 (60%) had no previous treatment, and 26 (40%) had relapsed or refractory disease. A total of 21 patients had a 17p deletion or TP53 mutation, and 45 had an unmutated IGHV status. Patients received two cycles of bendamustine debulking if they had an absolute lymphocyte count of at least 25,000/µL or a lymph node diameter of at least 5 cm—51 patients met these criteria. Then, all patients received six induction cycles and up to 24 months of maintenance with ofatumumab and ibrutinib.
After six induction cycles, the response rate was 92% (60 of 65 patients). Nine patients (14%) achieved minimal residual disease negativity in peripheral blood.
Two patients died of treatment-related causes: one 73-year-old woman died of sepsis and multiple organ failure after the sixth induction cycle, and one 73-year-old man died of ischemic cerebral infarction in the second maintenance cycle. Grade 3 adverse events occurred in 25 patients, and grade IV events were reported in 8 patients. Neutropenia (21%), infusion-related reactions (8%), and diarrhea (6%) were the most common grade 3 or 4 adverse events.
Disclosure: The authors’ disclosures can be found at haematologica.org.