Treatment of secondary central nervous system lymphoma with intrathecal rituximab, high-dose methotrexate, and R-DHAP followed by autologous stem cell transplantation : results of the HOVON 80 phase 2 study

Doorduijn, Jeanette K.; van Imhoff, Gustaaf W.; van der Holt, Bronno; Schouten, Harry C.; Schaafsma, Martijn R.; MacKenzie, Marius A.; Baars, Joke W.; Kersten, Marie Jose; Lugtenburg, Pieternella J.; van den Bent, Martin J.; Enting, Roelien H.; Spoelstra, Fokje M.; Poortmans, Philip; Bromberg, Jacoline E.C.

doi:10.1002/HON.2342

Title

Treatment of secondary central nervous system lymphoma with intrathecal rituximab, high-dose methotrexate, and R-DHAP followed by autologous stem cell transplantation : results of the HOVON 80 phase 2 study

Author

Doorduijn, Jeanette K.

van Imhoff, Gustaaf W.

van der Holt, Bronno

Schouten, Harry C.

Schaafsma, Martijn R.

MacKenzie, Marius A.

Baars, Joke W.

Kersten, Marie Jose

Lugtenburg, Pieternella J.

van den Bent, Martin J.

Enting, Roelien H.

Spoelstra, Fokje M.

Poortmans, Philip

Bromberg, Jacoline E.C.

Abstract

The prognosis of central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma is poor with 1-year survival historically at 0% to 20%. Aiming to improve these results, we performed a multicenter phase 2 study in patients with a CNS relapse, with or without concurrent systemic relapse. Treatment consisted of 2 cycles of R-DHAP alternating with high-dose methotrexate (MTX) and was combined with intrathecal rituximab. Responding patients received a third R-DHAP-MTX cycle followed by busulfan and cyclophosphamide myeloablative therapy and autologous stem cell transplantation. In patients with persistent cerebrospinal fluid lymphoma after cycle 1, the intrathecal rituximab was replaced by intrathecal triple therapy, with MTX. cytarabine, and dexamethasone. Thirty-six patients were included. Eighteen had evidence of cerebrospinal fluid lymphoma, 24 had brain parenchymal disease, and 20 (56%) had concurrent systemic disease. The overall response rate after 2 R-DHAP-MTX was 53% (19/36), with 22% (8/36) complete remission. Fifteen patients (42%) underwent a transplant. One-year progression-free survival was 19% (95% confidence interval, 9-34): 25% in patients without and 15% in patients with systemic disease. One-year overall survival was 25% (95% confidence interval, 12-40). This treatment regimen did not result in a major improvement of outcome of secondary CNS lymphoma, especially when concurrent systemic disease was present.

Language

English

Source (journal)

Hematological oncology. - Chichester

Publication

Chichester : 2017

ISSN

0278-0232

DOI

10.1002/HON.2342

Volume/pages

35 :4 (2017) , p. 497-503