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
Maciej Tatarczuch, Katharine Louise Lewis, Ashray Gunjur, Briony Shaw, Li Mei Poon, Erin Paul, Matthew Ku, Mark Wong, Sylvia Ai, Ashley Beekman, Pietro R. Di Ciaccio, Michael Krigstein, Joel Wight, Caitlin Coombes, Michael Gilbertson, Amanda Tey, Jake Shortt, Chandramouli Nagarajan, Dipti Talaulikar, Nada Hamad, Sumita Ratnasingam, Shir-Jing Ho, Tara Cochrane, Eliza A. Hawkes, Chan Y. Cheah, Stephen Opat, Gareth P. Gregory
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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/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.