A combination treatment approach consisting of venetoclax, lenalidomide, and rituximab was well tolerated and demonstrated efficacy for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL), according to results from the phase Ib VALERIA trial presented by Mats Jerkeman, MD, of the Lund University and Skane University Hospital in Sweden, at the 62nd American Society of Hematology Annual Meeting & Exposition.
Patients with MCL in this trial had measurable disease that became R/R after at least one rituximab-containing chemotherapy regimen. The primary endpoint of the study was the six-month overall response rate (ORR).
There were three main cohorts in this study:
- Cohort A: lenalidomide 15 mg daily and venetoclax 400 mg daily
- Cohort B: Lenalidomide 20 mg daily and venetoclax 400 mg daily
- Cohort C: Lenalidomide 20 mg daily and venetoclax 800 mg daily
All patients received rituximab 375 mg/m2 on day one in cycle one and then 1,400 mg on subsequent days in cycles one through 11.
A total of three patients in each cohort were enrolled across five centers in Sweden and Norway. There were no dose-limiting toxicities in cohorts A and B. In cohort C, two of three patients had a grade 3/4 infection.
The median age of the patient population was 71 years, with patients receiving a median of two prior regimens. A total of three patients had progressed after ibrutinib initiation.
The most frequent adverse event was hematologic toxicity, with 19 out of 20 patients experiencing grade 3/4 neutropenia and six experiencing grade 3/4 thrombocytopenia.
There were 16 patients evaluable for efficacy after a median follow up of five months. The ORR was 56% and included five complete responses (CRs) and four partial responses. The median duration of response as well as the progression-free survival have not yet been reached. Approximately 20% have stopped therapy in CR and molecular remission, and six are currently on treatment. Up to eight patients have progressed, of which four have died.
All of the patients evaluable for minimal residual disease at six months achieved molecular remission in blood, and five of these patients had molecular remission in bone marrow.
