Sequential high-dose methotrexate and cytarabine administration improves outcomes in real-world patients with primary central nervous system lymphoma: A report from the Australasian Lymphoma Alliance.

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/m2 (range 1-64 g/m2) and 12 g/m2 (0-32 g/m2) respectively. Using 14 g/m2 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.