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
Affiliations
Maciej Tatarczuch
Monash Haematology, Monash Health Centre Melbourne Victoria Australia
Katharine Louise Lewis
Department of Haematology Sir Charles Gairdner Hospital Perth Western Australia Australia
Ashray Gunjur
Department of Oncology Austin Health Melbourne Victoria Australia
Briony Shaw
Monash Haematology, Monash Health Centre Melbourne Victoria Australia
Li Mei Poon
National Cancer Institute Singapore Singapore
Erin Paul
Department of Haematology St. Vincent's Hospital Melbourne Victoria Australia
Matthew Ku
Department of Haematology St. Vincent's Hospital Melbourne Victoria Australia
Mark Wong
Department of Haematology Gold Coast University Hospital Southport Queensland Australia
Sylvia Ai
Department of Haematology St George Hospital Kogarah New South Wales Australia
Ashley Beekman
Department of Haematology University Hospital Geelong Geelong Victoria Australia
Pietro R. Di Ciaccio
Department of Haematology St. Vincent's Hospital Sydney New South Wales Australia
Michael Krigstein
Department of Haematology St. Vincent's Hospital Sydney New South Wales Australia
Joel Wight
Department of Haematology and Bone Marrow Transplantation Townsville University Hospital Douglas Queensland Australia
Caitlin Coombes
College of Health and Medicine Australian National University Canberra Australia
Michael Gilbertson
Monash Haematology, Monash Health Centre Melbourne Victoria Australia
Amanda Tey
Pharmacy Department Monash Health Melbourne Victoria Australia
Jake Shortt
Monash Haematology, Monash Health Centre Melbourne Victoria Australia
Chandramouli Nagarajan
SingHealth, Duke‐NUS Blood Cancer Centre Singapore Singapore
Dipti Talaulikar
College of Health and Medicine Australian National University Canberra Australia
Nada Hamad
Department of Haematology St. Vincent's Hospital Sydney New South Wales Australia
Sumita Ratnasingam
Department of Haematology University Hospital Geelong Geelong Victoria Australia
Shir‐Jing Ho
Department of Haematology St George Hospital Kogarah New South Wales Australia
Tara Cochrane
Department of Haematology Gold Coast University Hospital Southport Queensland Australia
Eliza A. Hawkes
Olivia Newton John Cancer Research Institute at Austin Health Melbourne Victoria Australia
Chan Y. Cheah
Department of Haematology Sir Charles Gairdner Hospital Perth Western Australia Australia
Stephen Opat
Monash Haematology, Monash Health Centre Melbourne Victoria Australia
Gareth P. Gregory
Monash Haematology, Monash Health Centre Melbourne Victoria Australia
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.
