Induction with ibrutinib and rituximab followed by a short course of consolidative chemotherapy is safe and effective in young patients with mantle cell lymphoma (MCL), according to results from the WINDOW-1 study published in The Lancet Oncology.
WINDOW-1 was a single-arm, phase 2 trial (ClinicalTrials.gov Identifier: NCT02427620) designed to determine the activity and safety of an initial chemotherapy-free period with ibrutinib-rituximab induction to achieve the best response, followed by a shortened chemoimmunotherapy regimen consisting of rituximab plus hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HCVAD) and alternating methotrexate-cytarabine as consolidation in previously untreated patients with MCL.
The study enrolled 131 patients. Among these, 36% had high-risk MCL, 33% had intermediate-risk disease, 31% had low-risk disease, 11% had aggressive MCL, 50% had high Ki-67 (≥30%), and 32% had TP53 aberrations.
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Treatment was given in 2 parts. In part A, patients received 12 cycles of ibrutinib-rituximab induction. In part B, patients received a shortened course of R-HCVAD alternating with methotrexate-cytarabine for 4 to 8 cycles, depending on whether patients had a complete response (CR) or partial response in part A. Patients received a median of 7 cycles in part A and 4 cycles in part B.
For part A, the 16-week overall response rate (ORR) was 89%, and the CR rate was 14%. For part B, the best ORR was 90%, and the CR rate was 89%.
At a median follow-up of 42 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 3-year PFS rate was 79%, and the 3-year OS rate was 95%.
The researchers noted a higher risk of progression among patients with a Ki-67 of 30% or higher (P =.017), a Ki-67 of 50% or higher (P =.0011), blastoid or pleomorphic MCL (P =.0013), high-risk MCL international prognostic index (P =.0041), and complex karyotype (P =.041).
The most common grade 3-4 adverse events were lymphocytopenia (14%), skin rash (12%), thrombocytopenia (9%), infections (8%), and fatigue (8%) in part A and lymphocytopenia (73%), leukocytopenia (32%), thrombocytopenia (30%), and neutropenia (20%) in part B. There were no treatment-related deaths.
The researchers wrote that this treatment approach “allowed minimization of the number of chemotherapy cycles, thereby reducing the adverse events associated with chemotherapy.”
“Newer trials bringing the next-generation Bruton’s tyrosine kinase inhibitors into the frontline setting might obviate the need for chemotherapy altogether in patients with mantle cell lymphoma,” the researchers concluded.
Disclosures: This research was supported by Pharmacyclics and Janssen. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Wang ML, Jain P, Zhao S, et al. Ibrutinib–rituximab followed by R-HCVAD as frontline treatment for young patients (≤65 years) with mantle cell lymphoma (WINDOW-1): a single-arm, phase 2 trial. Lancet Oncol. Published online January 21, 2022. doi:10.1016/S1470-2045(21)00638-0
