Triplet Combination Shows Moderate But Insufficient Results in R/R B-Cell NHL Patients

New results from a phase 2 LYSA group study of treatment for patients with relapsed or refractory B non-Hodgkin’s lymphoma (NHL) showed that induction and maintenance therapy with the combination of atezolizumab (ATE), obinutuzumab (OBI), and venetoclax (VEN) features moderate efficacy and manageable toxicity. However, these results, published in the British Journal of Haematology, may be insufficient to merit further development of the combination treatment evaluated.

This open-label, multicenter, nonrandomized study was led by Charles Herbaux, MD, PhD, from the University of Montpellier, France, and was focused on the analysis of treatment with the ATE-OBI-VEN combination in three cohorts of patients with relapsed or refractory B NHL.

Dr. Herbaux and colleagues wrote that after the moderate to unsatisfying results, they determined that “identifying patients most likely to benefit from this regimen remains speculative.” Moreover, the study “provides valuable insights but has several limitations that should be acknowledged.”

This multicenter trial was focused on patients with relapsed or refractory B NHL who had received at least one prior anti–CD20-containing immunochemotherapy regimen and included 136 patients aged 18 years and older, the majority of whom were older adult males. The enrollees were allocated to three cohorts according to lymphoma subtype. Cohort 1 comprised 58 patients with follicular lymphoma (FL); cohort 2, 58 patients with diffuse large B-cell lymphoma (DLBCL); and cohort 3, 20 patients with marginal zone lymphoma (MZL).

This trial took place over 18 months with a 6-month induction period that included eight cycles of the ATE-OBI-VEN combination, followed by a 12-month maintenance period with continuous administration of VEN and administration of ATE every 3 weeks. ATE and OBI were given intravenously, and VEN was given orally. The trial only measured a single dose level for the combination of drugs, and no phase 1 design was used.

The primary end points for cohorts 1 and 2 were not met. At the end of induction (EOI), the ATE-OBI-VEN combination produced an overall response rate (ORR) of 53.6% in the FL cohort and 23.6% in the DLBCL cohort versus the respective minimums of 70% and 48% expected by the researchers. Median progression-free survival (PFS) was 11.0 and 2.7 months in the FL and DLBCL cohorts, respectively. In the MZL cohort, the ORR at EOI was evaluated at 66.7%, but the investigators made no hypothesis in regard to this population. The most frequent adverse events (AEs) observed were cytopenias, and the investigators considered 7.4% of the observed autoimmune AEs to be linked to the ATE-OBI-VEN combination.

Although the authors of the study had seen moderate success in the MZL cohort as compared with the other cohorts, the triplet regimen of ATE plus OBI and VEN did not meet the efficacy threshold required for further development as treatment for DLBCL and FL. The authors maintain that more research is needed due to the limitations of the study.