The combination of the anti-CD20 antibody obinutuzumab and venetoclax in chronic lymphocytic leukemia shows a high overall response rate and compares favorably with established therapies, according to a new report.
The ongoing, open-label, phase 2 study examined the outcomes of six induction cycles, followed by up to 24 months of maintenance treatment withand , in 66 patients with chronic lymphocytic leukemia (CLL). Of the 63 patients included in the efficacy analysis, 34 (54%) had treatment-naive and 29 (46%) had relapsed or refractory disease.
After an initial debulking with two cycles of bendamustine, followed by the obinutuzumab and venetoclax treatment, researchers observed an overall response rate of 95%. By the end of the induction phase, all the treatment-naive patients responded, as did 90% of the relapsed or refractory patients. Five patients had achieved complete remission and 55 patients had a partial response, the researchers reported in.
By 15 months, both progression-free and overall survival was 100% among treatment-naive patients, while progression-free survival was 83% and overall survival was 90% among the relapsed or refractory patients at this point.
Researchers observed minimal residual disease (MRD) negativity in the peripheral blood of 91% of treatment-naive patients and 83% of relapsed or refractory patients.
The combination of venetoclax and obinutuzumab was chosen based on earlier trial data, which suggested a synergy between venetoclax and the less-potent anti-CD20 antibody rituximab.
Paula Cramer, MD, from the German CLL Study Group at University Hospital, Cologne, and her coauthors described the efficacy of the venetoclax and obinutuzumab combination as “encouraging.”
“The combination of venetoclax and obinutuzumab yields fast responses with MRD-negative remissions in most patients,” they wrote. “Based on the experience with venetoclax combined with rituximab in another trial and with venetoclax and obinutuzumab in this and another study, these deep, MRD-negative remissions seem to last for a substantial time after treatment termination.”
Of the 677 adverse events, 427 (63%) were deemed to be related to the study treatment, and 69 of these were serious adverse events.
The most common of these were infections, experienced by four patients during the debulking with bendamustine, and 18 cases in 11 patients during the induction treatment. This included pneumonia, sepsis and cytomegalovirus infection, as well as neutropenia and thrombocytopenia.
Six patients also experienced infusion-related reactions, four had coronary artery disorder – one during debulking and three during induction – and there were three cases of neoplasms.
Five patients in the relapsed or refractory group died; three of sepsis related to study treatment, and two from unrelated Richter’s transformation.
“With three deaths from sepsis in 66 enrolled patients, the treatment-related mortality seems high; however, in cases of low patient numbers, a few patients can have a substantial effect on the overall results,” the researchers wrote.
The study was funded by F Hoffmann-La Roche and AbbVie. Several authors reported research funding, grants, honoraria and other support from the pharmaceutical industry, including from the study sponsors.
SOURCE: Cramer P et al. Lancet Oncol. 2018 Aug 13. .