Venetoclax/Obinutuzumab Effective in CLL

September 4, 2018

A study shows bendamustine followed by venetoclax and obinutuzumab was active in treatment-naive or relapsed/refractory CLL.

The combination of bendamustine followed by venetoclax and obinutuzumab was active in patients with treatment-naive or relapsed/refractory chronic lymphocytic leukemia (CLL), according to the results of the phase II CLL2-BAG study published in Lancet Oncology.

Specifically, at the end of the induction period, there was a 95% overall response rate and 87% of patients had minimal residual disease (MRD) negativity in peripheral blood, regardless of past treatment, physical fitness, and genetic factors.

“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,” wrote Paula Cramer, MD, of University Hospital Cologne, Germany, and colleagues. “Thus, the combination of venetoclax with an anti-CD20 antibody might constitute a novel paradigm of treatment and overcome the need for an indefinite treatment, as is the case with the other approved targeted agents to maintain responses in chronic lymphocytic leukemia.”

Previously, only preliminary data were available on the combination of venetoclax with an anti-CD20 antibody obinutuzumab. The CLL2-BAG trial was started to look at this combination in patients with CLL.  The phase II trial included 66 patients aged 18 or older with CLL requiring treatment. Patients who had a relevant tumor load received sequential treatment of debulking with two cycles of bendamustine followed by induction and maintenance with obinutuzumab and oral venetoclax. The primary endpoint was the overall response by investigator assessment at the end of induction.

Of the enrolled patients, 35 were treatment-naive and 31 had relapsed or refractory disease. Three patients were excluded from the efficacy analysis because they did not receive enough cycles of treatment.

At the end of the induction period, 60 of 63 patients (95%) had response to treatment. All patients with treatment-naive disease responded. Eighty-seven percent of patients achieved MRD negativity in the peripheral blood, including 91% of treatment-naive patients and 83% of relapsed or refractory patients.

With a median follow-up of 16 months, 4 progressions and 3 deaths occurred in patients with relapsed or refractory disease. Therefore, the median progression-free and overall survival were not reached in either cohort.

Commonly occurring grade 3/4 adverse events during debulking were neutropenia (11%), anemia (11%), thrombocytopenia (6%), and infection (6%). The most common grade 3/4 events during induction were neutropenia (44%), infection (14%), thrombocytopenia (12%), infusion-related reactions (8%), and secondary primary malignancy (6%).

“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 noted.

They concluded that, “The efficacy of the study treatment regimen achieved in this mixed population is encouraging, especially since the MRD negativity rate of 91% in the peripheral blood in the treatment-naive cohort is among the highest reported so far in chronic lymphocytic leukemia.”