Rapid Readouts: Ibrutinib Plus Rituximab and Venetoclax Followed by Risk-Stratified Chemoimmunotherapy in Young Patients With Previously Untreated MCL

Preetesh Jain, MD, PhD, discusses data from the following study:

• Ibrutinib plus rituximab and venetoclax followed by risk-stratified observation or short-course R-hyper-CVAD [rituximab, cyclophosphamide, vincristine, doxorubicin hydrochloride, dexamethasone]–methotrexate in young patients with previously untreated mantle cell lymphoma: phase 2 WINDOW-2 clinical trial. (Blood. 2020;136:35-36)
  • The objective of this study is to report results in young patients with previously untreated mantle cell lymphoma treated with IRV [ibrutinib, rituximab, venetoclax] followed by observation or short-course R-hyper-CVAD–methotrexate.
  • IRV is a chemotherapy-free combination option.
  • 50 patients were enrolled to receive IR [ibrutinib, rituximab] induction for an initial 4 cycles, restaging at cycle 4, then IRV for up to 8 cycles. Patients were then risk-stratified (high, moderate, or low) to receive R-hyper-CVAD–methotrexate consolidation or observation, followed by 2 years of IRV maintenance.
  • Safety and efficacy outcomes were assessed in the population:
    • Overall response rate (ORR) was assessed at 96% with a complete response in 92% before consolidation.
    • Best ORR after consolidation in medium- and high-risk patients was 96%.
    • The median number of cycles of IRV to reach best response was 8.
    • Grade 3/4 toxicities with initial IRV were 3% mucositis and 10% each with myelosuppression, fatigue, myalgia, and rashes.
    • Grade 3 atrial flutter developed in 1 patient with initial IRV, while none had bleeding or bruising.
    • Among 35 patients who received consolidation, grade 3/4 toxicities were 46% neutropenia, 30% anemia, and 40% thrombocytopenia.
  • Conclusions:
    • IRV induced unprecedented efficacy before chemotherapy consolidation.
    • Thirteen patients (26%) came off study: 5 for adverse events, 3 for on-study deaths, 2 for patient choice, 2 lost to follow-up, and 1 for disease progression.
    • Overall, 5 patients died (3 on trial and 2 off, 1 from progressive disease and another from COVID-19).
    • WINDOW-2 suggests that patients with low-risk mantle cell lymphoma may not need chemotherapy, but further follow-up is warranted.
    • Further studies on predictors of response, minimal residual disease, and clonal evolution are ongoing.