Literature DB >> 35441948

High-dose methotrexate and rituximab induction regimen in immunocompetent patients with primary CNS lymphoma: a retrospective single-center study of survival predictors.

Mina Lobbous1,2, L Burt Nabors3,4, Andrew B DeAtkine5, Moaaz Abdelrashid6, Zach Tucker1, Amitkumar Mehta7, James M Markert6,2, Jinsuh Kim8, John B Fiveash9, Robert A Oster2,10.   

Abstract

PURPOSE: Primary Central Nervous System Lymphoma (PCNSL) is an aggressive tumor that is confined to the CNS. Although the provision of high-dose methotrexate (HD-MTX) has remarkably improved outcomes in PCNSL patients, the optimal treatment regimens and standard MTX dose for induction therapy have been largely controversial. Herein, we sought to explore the impact of adjuvant rituximab and different dosages of induction HD-MTX on survival outcomes of immunocompetent patients with PCNSL.
METHODS: In this study, we examined patients with PCNSL treated at a single NCI-designated comprehensive cancer center to evaluate their survival outcomes. We conducted a retrospective analysis of 51 immunocompetent patients with PCNSL who received their induction chemotherapy at the University of Alabama at Birmingham (UAB) between 2001 and 2019. Only adult patients with a confirmed diagnosis of PCNSL who had either HD-MTX alone or in combination with rituximab were included. Patients' demographics, clinical characteristics, and survival data were collected and analyzed.
RESULTS: There is no significant difference in survival among patients who received MTX alone versus MTX plus rituximab (HR = 0.996 (95% CI: 0.398-2.493), p = 0.994). Lower doses of MTX were associated with worse survival outcomes (HR = 0.680 (95% CI: 0.530-0.872), p = 0.002); however, this difference in survival was not significant when adjusted to age (HR = 0.797 (95% CI: 0.584-1.088), p = 0.153).
CONCLUSION: Our experience challenges the role of rituximab in PCNSL during induction therapy. Our study also highlights the shorter survival in elderly patients with PCNSL which can be related, to some extent, to the relatively lower doses of HD-MTX. There is an unmet need to establish a consensus on the most effective upfront regimen in PCNSL through prospective studies.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Entities:  

Keywords:  HD-MTX; Methotrexate; Outcomes; PCNSL; Primary CNS Lymphoma; Rituximab

Mesh:

Substances:

Year:  2022        PMID: 35441948     DOI: 10.1007/s11060-022-04004-9

Source DB:  PubMed          Journal:  J Neurooncol        ISSN: 0167-594X            Impact factor:   4.130


  28 in total

1.  Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

Authors:  Markus Joerger; Andrés J M Ferreri; Stephan Krähenbühl; Jan H M Schellens; Thomas Cerny; Emanuele Zucca; Alwin D R Huitema
Journal:  Br J Clin Pharmacol       Date:  2012-02       Impact factor: 4.335

Review 2.  Rational administration schedule for high-dose methotrexate in patients with primary central nervous system lymphoma.

Authors:  M Joerger; A D R Huitema; G Illerhaus; A J M Ferreri
Journal:  Leuk Lymphoma       Date:  2012-05-21

Review 3.  Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology.

Authors:  Khê Hoang-Xuan; Eric Bessell; Jacoline Bromberg; Andreas F Hottinger; Matthias Preusser; Roberta Rudà; Uwe Schlegel; Tali Siegal; Carole Soussain; Ufuk Abacioglu; Nathalie Cassoux; Martina Deckert; Clemens M F Dirven; Andrés J M Ferreri; Francesc Graus; Roger Henriksson; Ulrich Herrlinger; Martin Taphoorn; Riccardo Soffietti; Michael Weller
Journal:  Lancet Oncol       Date:  2015-07       Impact factor: 41.316

4.  CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009-2013.

Authors:  Quinn T Ostrom; Haley Gittleman; Jordan Xu; Courtney Kromer; Yingli Wolinsky; Carol Kruchko; Jill S Barnholtz-Sloan
Journal:  Neuro Oncol       Date:  2016-10-01       Impact factor: 12.300

Review 5.  Primary central nervous system lymphoma.

Authors:  Elizabeth R Gerstner; Tracy T Batchelor
Journal:  Arch Neurol       Date:  2010-03

6.  Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients.

Authors:  Wilhelm Küker; Thomas Nägele; Agnieska Korfel; Stefan Heckl; Eckhard Thiel; Michael Bamberg; Michael Weller; Ulrich Herrlinger
Journal:  J Neurooncol       Date:  2005-04       Impact factor: 4.130

Review 7.  Therapy of primary CNS lymphoma: role of intensity, radiation, and novel agents.

Authors:  Andrés José María Ferreri
Journal:  Hematology Am Soc Hematol Educ Program       Date:  2017-12-08

8.  Gene expression profiling suggests primary central nervous system lymphomas to be derived from a late germinal center B cell.

Authors:  M Montesinos-Rongen; A Brunn; S Bentink; K Basso; W K Lim; W Klapper; C Schaller; G Reifenberger; J Rubenstein; O D Wiestler; R Spang; R Dalla-Favera; R Siebert; M Deckert
Journal:  Leukemia       Date:  2007-11-08       Impact factor: 11.528

9.  High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study).

Authors:  K Fritsch; B Kasenda; E Schorb; P Hau; J Bloehdorn; R Möhle; S Löw; M Binder; J Atta; U Keller; H-H Wolf; S W Krause; G Heß; R Naumann; S Sasse; C Hirt; M Lamprecht; U Martens; A Morgner; J Panse; N Frickhofen; A Röth; C Hader; M Deckert; H Fricker; G Ihorst; J Finke; G Illerhaus
Journal:  Leukemia       Date:  2016-11-15       Impact factor: 11.528

10.  Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas.

Authors:  A J M Ferreri; E Guerra; M Regazzi; F Pasini; A Ambrosetti; A Pivnik; A Gubkin; A Calderoni; M Spina; A Brandes; F Ferrarese; A Rognone; S Govi; S Dell'Oro; M Locatelli; E Villa; M Reni
Journal:  Br J Cancer       Date:  2004-01-26       Impact factor: 7.640

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