From the Guidelines
Ibrutinib plus rituximab (ibr-R) is the recommended treatment for previously untreated mantle cell lymphoma (MCL) patients, due to its superior progression-free survival and favorable safety profile compared to R-CHOP/R-bendamustine. The ibrutinib regimen consists of ibrutinib 560mg daily plus rituximab (375mg/m² weekly for 4 weeks in cycle 1, then day 1 of cycles 3-8), followed by continuous ibrutinib maintenance until progression 1. This chemotherapy-free approach is particularly beneficial for high-risk patients with high MIPI scores or TP53 mutations, populations that typically respond poorly to conventional chemoimmunotherapy.
Some key points to consider when using ibr-R include:
- The 4-year PFS rate is 72% versus 54% for the standard chemoimmunotherapy arm 1
- Ibrutinib is associated with specific adverse events including atrial fibrillation, hypertension, and bleeding, requiring appropriate monitoring 1
- The ibr-R regimen demonstrated a more favorable safety profile with fewer grade 3-4 adverse events, particularly hematologic toxicities, compared to conventional chemoimmunotherapy 1
- Testing for MYD88 and CXCR4 mutation status is recommended for ibrutinib candidates, as these mutations may impact treatment outcomes 1
Overall, the use of ibr-R represents a paradigm shift in MCL treatment, offering an effective chemotherapy-free option with improved outcomes and quality of life for patients with previously untreated MCL.
From the Research
Ibr-R vs R-CHOP/BR Mantle Cell Trial Results
- The study 2 investigated the efficacy of ibrutinib in combination with rituximab (IR) in patients with indolent clinical forms of mantle cell lymphoma (MCL), showing a high rate of complete responses (80%) and undetectable minimal residual disease (87%).
- In contrast, the study 3 compared ibrutinib plus bendamustine and rituximab (Ibru + BR) to placebo plus bendamustine and rituximab in untreated MCL patients, demonstrating a significant improvement in progression-free survival (80.6 months vs 52.9 months).
- The combination of acalabrutinib with bendamustine-rituximab was also shown to improve progression-free survival in untreated MCL patients, with a median progression-free survival of 66.4 months compared to 49.6 months in the placebo arm 4.
- A network meta-analysis 5 suggested that ibrutinib plus bendamustine and rituximab (Ibru + BR) may be superior to R-CHOP in newly diagnosed patients with MCL ineligible for intensive therapy, with a hazard ratio of 0.35 for progression-free survival.
- The study 6 investigated the safety and efficacy of ibrutinib in combination with R-CHOP for patients with previously untreated CD20-positive B-cell non-Hodgkin lymphoma, showing that ibrutinib is well tolerated when added to R-CHOP and may improve responses in patients with B-cell non-Hodgkin lymphoma.
Comparison of Treatment Regimens
- Ibru + BR vs R-CHOP: Ibru + BR may be superior to R-CHOP in terms of progression-free survival, with a hazard ratio of 0.35 5.
- Ibru + BR vs VR-CAP: Ibru + BR may also be superior to VR-CAP, with a hazard ratio of 0.55 for progression-free survival 5.
- Acalabrutinib + BR vs placebo + BR: Acalabrutinib + BR was shown to improve progression-free survival compared to placebo + BR, with a median progression-free survival of 66.4 months vs 49.6 months 4.