Micrograph showing CLL
Bendamustine followed by obinutuzumab and venetoclax produces a high overall response rate in chronic lymphocytic leukemia (CLL), according to research published in The Lancet Oncology.
In an ongoing, phase 2 study, researchers examined the outcomes of this treatment in 66 patients with CLL.
Patients underwent initial debulking with two cycles of bendamustine, received six cycles of obinutuzumab and venetoclax for induction, and could receive up to 24 months of maintenance with obinutuzumab and venetoclax.
Efficacy
Of the 63 patients included in the efficacy analysis, 34 (54%) were treatment-naïve, and 29 (46%) had relapsed or refractory disease.
At the end of induction, the overall response rate was 95% (60/63), with responses observed in 100% (34/34) of treatment-naive patients and 90% (26/29) of relapsed/refractory patients.
Five patients (8%) achieved complete remission (CR)—3 who were treatment-naïve and 2 with relapsed/refractory disease.
Twenty patients (32%) had a clinical CR or CR with incomplete bone marrow recovery—14 who were treatment-naïve and 6 with relapsed/refractory disease.
Thirty-five patients (56%) had a partial response—17 who were treatment-naïve and 18 with relapsed/refractory disease.
By 15 months, both progression-free and overall survival were 100% among treatment-naive patients.
In the relapsed/refractory patients, progression-free survival was 83%, and overall survival was 90%.
Researchers observed minimal residual disease negativity in the peripheral blood of 91% (31/34) of treatment-naive patients and 83% (24/29) of relapsed/refractory patients. (Most patients did not have data for MRD in the bone marrow.)
Study author Paula Cramer, MD, from the German CLL Study Group at University Hospital, Cologne, and her colleagues described the efficacy of the combination as “encouraging.”
Safety
Safety data were available for all 66 patients. Of the 677 AEs, 427 (63%) were deemed related to study treatment, and 69 of these were serious AEs. Twelve patients had related, serious AEs during debulking, and 23 patients had related, serious AEs during induction.
The most common serious AEs were infections and cytopenias. There were four infections during debulking and 18 infections in 11 patients during induction. The most common infections were pneumonia and sepsis.
There were two cases of neutropenia during debulking and six cases in five patients during induction. There were four cases of thrombocytopenia in three patients during induction.
Other common treatment-related, serious AEs were:
- Infusion-related reactions—six cases during induction
- Coronary artery disorder—one case during debulking and three during induction
- Tumor lysis syndrome —one case during debulking and two during induction
- Neoplasms—two squamous cell carcinomas and one malignant melanoma during induction
- Increased creatinine—two cases during debulking.
Five patients in the relapsed/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.