Frontline Ibrutinib and Rituximab Are Safe to Use in Patients With Mantle Cell Lymphoma

Results from the WINDOW-1 signal promise for use of the R-HCVAD regimen in patients with mantle cell lymphoma.

The use of ibrutinib (Imbruvica) and rituximab (Rituxan) followed by R-HCVAD (rituximab-cyclophosphamide [Cytoxan], vincristine [Oncovin], dexamethasone [Decadron], doxorubicin [Adriamycin]) in young patients and untreated patients with mantle cell lymphoma has been found to be active and safe in a study published in Lancet Oncology.1

Overall response rate (ORR) was 98% (n = 128; 95% CI, 95%-100%).

The WINDOW-1 (NCT02427620) trial, a single-center, single-arm, phase 2 study, enrolled 131 patients between June 12, 2015, and Dec 6, 2018. This study consisted of 2 parts. In part A, patients received 12 cycles of the combination of oral ibrutinib (560 mg daily) andintravenous rituximab (375 mg/m2 weekly) for the first 4 weeks and then on day 1 of cycles 3 to 12. If patients from part A had a complete response, they were moved into part B where patients received 4 cycles of R-HCVAD alternating with methotrexate and cytarabine. If patients did not respond or had partial response, they received 2 cycles of R-HCVAD, alternating with methotrexate and cytarabine followed by reassessment up to 8 cycles. If stable disease or progression during R-HCVAD was recorded, the patient was taken off the study. The ORR after part A was the primary end point.

The most common grade 3 and 4 adverse events (AEs) in part A were lymphocytopenia in 19 (14%) patients, skin rash in 16 (12%) patients, thrombocytopenia in 12 (9%) patients, infections in 11 (8%), and fatigue in 10 (8%). Grade 3 and 4 AEs presented more commonly in patients in part B. The most common AEs in part B were lymphocytopenia (n = 96 [73%]), leukocytopenia (n = 42 [32%]), thrombocytopenia (n = 40 [30%]), and neutropenia (n = 26 [20%]). Investigators reported 1 death but deemed it to be unrelated to treatment.

Eligible patients must have been 65 years or younger, had serum bilirubin levels of less than 1.5 mg/dL, creatinine clearance of 30 mL/min or more, ECOG performance status of 2 or less, and cardiac ejection fraction of 50% or more as determined by echocardiogram.

The median age of patients was 56 years (range, 49-60). Fifty percent (n = 58) of the 117 patients had high Ki-67 of 30% or greater.

Results from this study show that the frontline combination of ibrutinib and rituximab is safe in young patients. This treatment regimen reduced the number of chemotherapies which limited the number of AEs caused by chemotherapy. Investigators are expecting to see decreased need for chemotherapy as new trials experiment with next generation Bruton’s tyrosine kinase inhibitors as a frontline treatment for mantle cell lymphoma.


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. Published online January 21, 2022. Lancet Oncol. 2022;S1470-2045(21)00638-0. doi:10.1016/S1470-2045(21)00638-0