Phase I/II study of acalabrutinib, venetoclax, and obinutuzumab in patients with relapsed/refractory and previously untreated Mantle Cell Lymphoma (MAVO)
This study started in patients uh with previously treated uh mantle cell lymphoma, which was the first cohort. And after proving that the regimen was safe, uh, it expanded to, uh, cohort B, which was a 24 patient cohort of treatment naive patients who were ineligible for autologous stem cell transplant or aggressive therapy, or had a TP53 aberrant mantle cell lymphoma, which was defined as a TP53 mutation on next-generation sequencing. Or overexpression of P53 protein by immunohistochemistry. As 9 of the 1st 12 patients went into a complete remission, the patient, the study was then uh expanded to include a 12-patient, uh, population, a cohort C who were treatment naive, uh, and who were eligible for, uh, autologous stem cell transplant or, uh, aggressive induction therapy without, uh, an aberrant TB53 status. Uh, so this study showed that there were high remission rates, uh, complete remission rates in all three cohorts. Uh, in cohort A, the complete remission rate was 75%, uh, cohort B, the complete remission rate was 83%, uh, and in cohort C, the complete remission rate was 100%. Um, the regimen was, uh, well tolerated, with the most common side effects being headache and bruising, which were all manageable grade 1 or 2. Uh, an interesting finding in this study was that, uh, within our cohort B, um, we had a subset of 17 patients who had a TP53 mutation, uh, which was not planned and higher than what we would have expected as only 10 to 20% of patients, uh, newly diagnosed have a TB53 mutation. But within this subset, uh, we were pleasantly surprised to find a complete remission rate of 82%. Uh, and an estimated 2-year progression-free survival of 82%, which compares favorably to other regimens. And this was with a median of 23 months of follow-up. Another unique aspect of this study was that in cohorts B and C, the treatment naive patients were eligible for time-limited therapy if they achieved a complete remission and had no evidence of microscopic disease, uh, using a minimal residual disease. So acaibrutinib and venene plaques were able to be discontinued as early as 10 cycles of therapy, and all patients completed 2 years of maintenance ofvinatuzumab. In cohort B of the 19 patients who had uh an invaluable MRD baseline study, uh, 15 patients achieved MRD negative complete remission and were able to discontinue acaibrutin and venetalax. So far, only 1 patient has relapsed after discontinuing therapy. So, in summary, this study adds to the current literature in mantle cell lymphoma, supporting the use of triplet chemotherapy-free regimens, um, especially in patients with a high-risk TP53 mutation. So based on the encouraging results of this study, a 16-patient expansion cohort is now open and rolling for untreated patients, specifically with the TP53 mutation, which will allow for a robust 33 patient cohort that will be reported in the future.
