Multicenter Randomized Phase II Study of R-MPV-A Chemoimmunotherapy With or Without Low-Dose Whole-Brain Radiotherapy for Newly-Diagnosed Primary CNS Lymphoma.
Article
Omuro, Antonio, DeAngelis, Lisa M, Polley, Mei-Yin C et al. (2025). Multicenter Randomized Phase II Study of R-MPV-A Chemoimmunotherapy With or Without Low-Dose Whole-Brain Radiotherapy for Newly-Diagnosed Primary CNS Lymphoma.
. NEURO-ONCOLOGY, noaf221. 10.1093/neuonc/noaf221
Omuro, Antonio, DeAngelis, Lisa M, Polley, Mei-Yin C et al. (2025). Multicenter Randomized Phase II Study of R-MPV-A Chemoimmunotherapy With or Without Low-Dose Whole-Brain Radiotherapy for Newly-Diagnosed Primary CNS Lymphoma.
. NEURO-ONCOLOGY, noaf221. 10.1093/neuonc/noaf221
Methotrexate-based chemoradiotherapy is effective in primary central nervous system lymphoma (PCNSL) but carries a risk of severe neurotoxicity. In a single-arm study, a regimen with methotrexate, procarbazine, vincristine and cytarabine was combined with rituximab (R-MPV-A) and substantially reduced doses of whole-brain radiotherapy (LD-WBRT), resulting in excellent progression-free survival (PFS) and overall survival (OS). Because R-MPV-A had never been tested without radiation, we sought to evaluate the efficacy of R-MPV-A with and without LD-WBRT, as well as determining if such low radiotherapy doses influenced disease control and/or neurotoxicity.
Methods
Patients were randomized to receive R-MPV-A alone (Chemo arm) or combined with LD-WBRT (ChemoRT arm), given at 2,340 cGy (180cGy X13). Primary endpoint was intent-to-treat (ITT) PFS. A sample size of 89 would provide 80% power to detect a hazard ratio (HR) of 0.63 (one-sided alpha = 0.15).
Results
Ninety-one patients were randomized, with 44 analyzed in the ChemoRT and 46 in the Chemo arm. Median age was 66 and 59.5, respectively. R-MPV-A was well tolerated, achieving complete response rate of 92.3% (ChemoRT) and 76.3% (Chemo). After median follow-up of 4.6 years, median PFS was not reached (ChemoRT) vs 2.1 years (Chemo), HR = 0.47 (p = 0.007; 95% CI: 0.26 to 0.87). The 2-year PFS was 78.7% vs 54%, respectively. Differences in OS did not reach statistical significance (HR 0.71; p = 0.33). Neuropsychological evaluation showed no differences in cognitive outcomes, with several tests favoring ChemoRT.
Conclusions
R-MPV-A is a highly efficacious and safe regimen with or without LD-WBRT. LD-WBRT contributes to disease control and increases PFS in PCNSL.
