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Abstract Background Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined. Methods We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B‐cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high‐dose methotrexate (HD‐MTX) containing chemotherapy regimens: MPV/Ara‐C (HD‐MTX, procarbazine, and vincristine, followed by cytarabine Ara‐C) ( n = 94, 50%), MATRix (HD‐MTX, Ara‐C, thiotepa, and rituximab) ( n = 19, 10%), HD‐MTX/Ara‐C ( n = 31, 16%), HD‐MTX monotherapy ( n = 35, 18%) and MBVP (HD‐MTX, carmustine, teniposide, prednisolone) ( n = 11, 6%). Results Cumulative median HD‐MTX and Ara‐C doses were 17 g/m 2 (range: 1–64 g/m 2 ) and 12 g/m 2 (0–32 g/m 2 ) respectively. Using 14 g/m 2 as the reference dose, the median HD‐MTX relative dose intensity (HD‐MTX‐RDI) was 1.25 (0.27‐4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD‐MTX. At a median follow‐up of 3.41 years (0.06–9.42), progression‐free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara‐C cohort (2‐year PFS 74%, 2‐year OS 82%; p = 0.0001 and p = 0.0024 respectively). On multivariate analysis, MPV/Ara‐C administration and HD‐MTX‐RDI > 0.75 were associated with longer PFS and OS. Conclusion Sequential, response‐adapted approaches can improve outcomes, even in older patients who are ineligible for a high‐intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.
Tatarczuch et al. (Fri,) studied this question.
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