The GREEN trial analyzed treatment with obinutuzumab monotherapy or obinutuzumab plus chemotherapy for patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia.
The combination of obinutuzumab (Gazyva) plus chemotherapy, beyond the already approved obinutuzumab plus chlorambucil (G-Clb) regimen, was supported as a promising first-line treatment option for patients with previously untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), according to data published in the British Journal of Haematology.
Data from the single-arm phase 3 GREEN trial (NCT01905943) also found a tolerable safety profile for obinutuzumab consistent with existing risk-management strategies. More, an analysis of biomarkers supported its efficacy across subgroups by cytogenetics.
The patients included in the trial analysis received 1000 mg of obinutuzumab either alone or in combination with chemotherapy—which included either fludarabine and cyclophosphamide (G-FC) for fit patients or bendamustine (G-benda) for nonfit patients. The primary end point of the research was safety, with a secondary end point focused on efficacy with the therapeutics.
“The GREEN study final analysis provides further evidence to support G-Clb as a treatment option for non-fit, [first-line] patients with CLL,” wrote the investigators who were led by Stephanie Stilgenbauer, MD. “It also supports G-Benda and G-FC as potential treatment options for fit and non-fit [first-line] CLL and for relapsed/refractory CLL patients who are eligible to receive chemoimmunotherapy.”
Overall, 630 patients were assigned to receive first-line treatment, while 341 patients received treatment for R/R CLL.
There were no new safety signals noted in the data, with grade 3 or greater adverse events (AEs) occurring in 82.7% of patients on first-line therapy and in 84.5% in the R/R setting. Serious AEs occurred in 58.1% and 62.5%, respectively. Specifically, neutropenia (frontline, 50.5% and R/R, 53.4%) and thrombocytopenia (14.6% and 19.1%, respectively) were the most common grade 3 or greater AEs in each patient cohort.
When expanding the analysis, patients treated with obinutuzumab monotherapy, G-benda, and G-FC with unmutated IGHV saw shorter progression-free survival rates. More, minimal residual disease negativity was greatest in the cohort of patients treated with G-FC in the frontline.
“The GREEN study was non-comparative with no formal statistical testing and no power calculation,” wrote the investigators. “The final analysis was performed at the end of the study, which was 30 months after enrollment of the last patient, or sooner, if one of the following was documented for all treated patients: withdrawal from the study, loss to follow-up, death or study termination.”
The noncomparative/nonrandomized design of the GREEN trial coupled with the potential for investigator bias when determining patient allocation to cohorts/treatment could be potential limitations of the data. More, higher than expected AEs and discontinuations were observed due to every patient being analyzed as treated, regardless of if they discontinued treatment before chemotherapy.
“Baseline levels of quality of life (QoL), physical functioning, and fatigue remained stable or improved over the course of treatment,” wrote the investigators. “CLL and its treatments can profoundly affect QoL, particularly in R/R patients; it is encouraging that the combinations explored here indicated no deterioration in QoL with the [obinutuzumab]–based combinations.”
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. British Journal of Haematology. doi: 10.1111/bjh.17326