The final analysis of the phase 3b GREEN trial confirmed the toxicity profile of obinutuzumab among patients with newly diagnosed or previously treated chronic lymphocytic leukemia (CLL), according to a report published in the British Journal of Haematology.
After the approval of obinutuzumab, regulatory authorities mandated the GREEN trial. The primary analysis of the GREEN trial (ClinicalTrials.gov Identifier: NCT01905943) demonstrated that obinutuzumab had a manageable toxicity profile as monotherapy or in combination with chemotherapy among patients with or without previous treatment for CLL. The final analysis includes an additional 18 months of follow-up, for a total median of 40 to 50 months among treatment groups.
The open-label, nonrandomized, phase 3b GREEN safety trial evaluated 972 patients with CLL treated with obinutuzumab monotherapy or obinutuzumab plus chlorambucil, bendamustine, or fludarabine and cyclophosphamide (FC). The study was not designed to be comparative; there was neither power calculation nor formal statistical testing performed.
Grade ≥3 adverse events occurred among 82.7% of previously untreated and 84.5% of previously treated patients, with the most common including neutropenia, thrombocytopenia, anemia, and pneumonia. Serious adverse events occurred among 58.1% and 62.5% of patients without or with prior therapy, respectively, with the most common including pneumonia and neutropenia.
There were 7.5% and 4.7% of previously untreated or treated patients, respectively, who developed tumor lysis syndrome, all of which were grade ≥3 except for a single grade 1 event. There were 2 deaths due to tumor lysis syndrome in the obinutuzumab plus bendamustine group.
Adverse events were attributed to 12% of death, including 8.9% among patients who were previously untreated and 17.9% among those previously treated. The most common reason for death was pneumonia.
Median progression-free survival was 30.2 months with obinutuzumab monotherapy, and 31.8 months, 58.0 months, and not yet reached in the obinutuzumab plus chlorambucil, bendamustine, or FC groups, respectively.
Median overall survival was not yet reached for any of the treatment groups. Patients without or with prior treatment in the obinutuzumab plus FC arm demonstrated the highest 4-year overall survival at 94% and 70%, respectively, followed by 85% and 68% in the obinutuzumab plus bendamustine arm, 83% and 59% in the monotherapy arm, and 67% and 54% in the obinutuzumab plus chlorambucil arm.
The authors concluded that “this final analysis of the GREEN study supports obinutuzumab plus chemotherapy, beyond the approved obinutuzumab-chlorambucil regimen, as a promising treatment option in both first-line and relapsed/refractory CLL, irrespective of the partner chemotherapy.”
Stilgenbauer S, Bosch F, Ilhan O, et al. Safety and efficacy of obinutuzumab alone or with chemotherapy in previously untreated or relapsed/refractory chronic lymphocytic leukaemia patients: final analysis of the phase IIIb GREEN study. Br J Haematol. Published online February 19, 2021. doi:10.1111/bjh.17326