MATILDE chemotherapy regimen for primary CNS lymphoma: Results at a median follow-up of 12 years

Objective: We report updated results at a median follow-up of 12 years of a phase II trial assessing first-line MATILDE chemotherapy and response-tailored radiotherapy in patients with primary CNS lymphomas (PCNSL). Methods: Forty-one HIV-negative patients (18-70 years; Eastern Cooperative Oncology Group performance status ≤3) with histologically confirmed PCNSL received 3 courses of MATILDE chemotherapy followed by whole-brain radiotherapy (WBRT). Chemotherapy activity was the primary endpoint. Results: Overall response rate was 76% (95% confidence interval [CI] 63%-89%) after chemotherapy and 83% (95% CI 71%-95%) after chemotherapy ± radiotherapy. At a median follow-up of 144 months (range 47-153), 31 patients experienced an event: relapse in 24, progressive disease in 3, and toxic death in 4, with a 5-year progression-free survival of 24% ± 8%. Two patients experienced a late relapse (100 and 101 months). Nine patients are alive and disease-free, 8 of whom are alive at >10 years, with a 5-year overall survival of 30% ± 7%. At 10 years from diagnosis, no patient showed chronic hematologic and nonhematologic toxicities, with a Mini-Mental State Examination score of ≥29 in all cases but one. Conclusions: At a median follow-up of 12 years, MATILDE regimen followed by WBRT confirmed the previously reported survival plateau, which further proves its long-lasting efficacy with acceptable neurologic deficits. Classification of evidence: This study provides Class IV evidence that in patients with PCNSL, MATILDE chemotherapy followed by response-tailored radiotherapy increases the probability of disease remission at 12 years.