Ibrutinib, Obinutuzumab, and Venetoclax in Relapsed and Untreated Patients with Mantle Cell Lymphoma: A Phase 1/2 Trial

Ibrutinib, Obinutuzumab, And Venetoclax In Relapsed And Untreated Patients With Mantle Cell Lymphoma: A Phase 1/2 Trial

In the journal Blood, an abstract published on February 18, 2021, reviews the utility of ibrutinib in combination with obinutuzumab and venetoclax in relapsed and untreated patients with mantle cell lymphoma.  The OAsis trial, was a single -arm multicenter prospective phase 1 / 2 clinical trial, aimed at determining the maximum tolerated dose of venetoclax when administered in combination with obinutuzumab and ibrutinib in patients with relapsed / refractory mantle cell lymphoma.  After the maximum tolerated dose of venetoclax was determined, expansion cohorts were open for relapsed untreated patients.  Efficacy and safety were secondary objectives.  Minimal residual disease which was determined by allele-specific oligonucleotide qPCR was also assessed.  

48 patients were enrolled over the course of 3 years.  No dose-limiting toxicity was reported with venetoclax 400 mg daily used in the extension arm.  75% of the relapse patients, n=18, and 53%, n=8 from the untreated patient group, experienced grade 3 or 4 adverse events.  The complete response rate assessed by PET scan after cycle 6 was 67% in the relapse and 86.6% in the untreated arm.  Minimal residual disease clearance was observed in 71.5% of relapse patients, 10 / 14 patients who were available for evaluation.  12 evaluable patients with untreated mantle cell lymphoma,, all had minimal residual disease clearance at the end of 3 cycles.  The medium follow-up for relapsed patients was 17 months.  The 2-year progression free survival was 69.5%, 95% confidence interval 52.9% – 91.4% and 60.6%, 95% confidence interval, 49.5% – 95.1% for overall survival.  The median follow-up was 14 months for the untreated patients, with a 1-year progression free survival of 93.3%, confidence interval 81.5% – 100%. 

The authors concluded “the combination of obinutuzumab, ibrutinib and venetoclax is well-tolerated and provides high response rates, including at the molecular level and relapsed untreated mantle cell lymphoma patients.”