(R)-GEMOX chemotherapy for unfit patients with refractory or recurrent primary central nervous system lymphoma: a LOC study
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Recurrent primary central nervous system lymphomas (PCNSL) have a very poor prognosis. For young and fit patients, intensive chemotherapy followed by autologous stem cell transplantation could be proposed at relapse. In the other cases (unfit or elderly patients), therapeutic options are limited with no consensual regimen. The poly-chemotherapy by (R)-GEMOX is associated with anti-tumor activity in systemic lymphomas and a favorable toxicity profile. Our objective was to evaluate the activity and tolerance of (R)-GEMOX in PCNSL patients enrolled in the French nation-wide LOC cohort. We retrospectively analyzed all refractory or recurrent patients included in the LOC network who benefited from (R)-GEMOX (rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatine 100 mg/m2). Administration, tolerance, and efficacy data were analyzed. Thirteen patients, treated in five different institutions, benefited from the (R)-GEMOX regimen from February 2013 to August 2017. At the initiation of (R)-GEMOX, median age was 71.4 years old (range, 49.5–82.5) and median Karnofsky performance status (KPS) was 60 (range, 40–80). Seven patients were in second line of treatment whereas the six others were in third line or over. All patients had received methotrexate-based polychemotherapy as first-line treatment except one. Overall response rate was 38% with two complete responses and three partial responses. Median progression-free survival was 3.2 months (95%CI: 0.2–6.2), and median overall survival was 8.2 months (95%CI: 0.6–15.8). Toxicity was mainly hematological including grade ¾ neutropenia (38%), lymphopenia (23%), and thrombopenia (23%). Older age (p = 0.046) and low KPS (p = 0.054) tended to be associated with a worse prognosis. (R)-GEMOX is associated with substantial response rate and favorable toxicity profile in unfit patients with recurrent PCNSL. (R)-GEMOX could be considered to be an additional option in patients with recurrent/refractory PCNSL.
KeywordsPrimary central nervous system lymphoma Recurrent Refractory Chemotherapy
LOC Network, AP-HM tissue bank AC 2013-1786, ARTC-sudassociation.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
For this type of study, formal consent is not required.
Informed consent was obtained from all individual participants included in the study.
- 12.Langner-Lemercier S, Houillier C, Soussain C, Ghesquières H, Chinot O, Taillandier L, Soubeyran P, Lamy T, Morschhauser F, Benouaich-Amiel A, Ahle G, Moles-Moreau MP, Moluçon-Chabrot C, Bourquard P, Damaj G, Jardin F, Larrieu D, Gyan E, Gressin R, Jaccard A, Choquet S, Brion A, Casasnovas O, Colin P, Reman O, Tempescul A, Marolleau JP, Fabbro M, Naudet F, Hoang-Xuan K, Houot R (2016) Primary CNS lymphoma at first relapse/progression: characteristics, management, and outcome of 256 patients from the French LOC network. Neuro-Oncol 18(9):1297–1303CrossRefGoogle Scholar
- 13.Jahnke K, Thiel E, Martus P, Herrlinger U, Weller M, Fischer L, Korfel A, on behalf of the German Primary Central Nervous System Lymphoma Study Group (G-PCNSL-SG) (2006) Relapse of primary central nervous system lymphoma: clinical features, outcome and prognostic factors. J Neurooncol 80(2):159–165CrossRefGoogle Scholar
- 14.Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F et al (2008) Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol Off J Am Soc Clin Oncol 26(15):2512–2518CrossRefGoogle Scholar
- 17.Gaviani P, Simonetti G, Innocenti A, Lamperti E, Botturi A, Silvani A (2016) Safety and efficacy of primary central nervous system lymphoma treatment in elderly population. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol 37(1):131–133Google Scholar
- 22.Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. - PubMed - NCBI [Internet]. [cité 28 juin 2018]. Disponible sur: https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/?term=Diagnosis+and+treatment+of+primary+CNS+lymphoma+in+immunocompetent+patients%3A+guidelines+from+the+European+Association+for+Neuro-Oncology
- 29.Choquet S, Grenier A, Houillier C, Soussain C, Moles MP, Gastinne T et al (2015) Very High Efficiency of ICE (Ifosfamide-Carboplatin-Etoposide) in Relapse/Refractory (R/R) Primary Central Nervous System (PCNSL) and Vitreo-Retinal (VRL) Non Hodgkin Lymphoma. a LOC Network Multicenter Retrospective Study on 58 Cases. Blood 126(23):1524–1524Google Scholar
- 30.Platine and cytarabine-based salvage treatment for primary central nervous system lymphoma. - PubMed - NCBI [Internet]. [cité 28 juin 2018]. Disponible sur: https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/21656329
- 32.Ghesquieres H, Houillier C, Chinot O, Choquet S, Molucon-Chabrot C, Beauchene P, Gressin R, Morschhauser F, Schmitt A, Gyan E, Hoang-Xuan K, Nicolas-Virelizier E, Chevrier M, Savignoni A, Turbiez I, Veillas F, Soumelis V, Soussain C (2016) Rituximab-Lenalidomide (REVRI) in Relapse or Refractory Primary Central Nervous System (PCNSL) or Vitreo Retinal Lymphoma (PVRL): Results of a « Proof of Concept » Phase II Study of the French LOC Network. BloodGoogle Scholar
- 35.Grommes C, Pastore A, Palaskas N, Tang SS, Campos C, Schartz D, Codega P, Nichol D, Clark O, Hsieh WY, Rohle D, Rosenblum M, Viale A, Tabar VS, Brennan CW, Gavrilovic IT, Kaley TJ, Nolan CP, Omuro A, Pentsova E, Thomas AA, Tsyvkin E, Noy A, Palomba ML, Hamlin P, Sauter CS, Moskowitz CH, Wolfe J, Dogan A, Won M, Glass J, Peak S, Lallana EC, Hatzoglou V, Reiner AS, Gutin PH, Huse JT, Panageas KS, Graeber TG, Schultz N, DeAngelis LM, Mellinghoff IK (2017) Ibrutinib unmasks critical role of Bruton tyrosine kinase in primary CNS lymphoma. Cancer Discov 7(9):1018–1029CrossRefGoogle Scholar
- 36.Choquet S, Houllier C, Bijou F et al (2016) Ibrutinib monotherapy in relapse or refractory primary CNS lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL). Result of the interim analysis of the iLOC phase II Study from the Lysa and the French LOC Network [abstract]. BloodGoogle Scholar
- 39.Graber J, Plato B, Moore D, Mawad R (2018) Two cases of Pembrolizumab therapy for CNS lymphoma (P6.136). Neurology 90(15 supplement) Disponible sur: http://n.neurology.org/content/90/15_Supplement/P6.136.abstract
- 40.Corazzelli G, Capobianco G, Arcamone M, Ballerini PF, Iannitto E, Russo F, Frigeri F, Becchimanzi C, Marcacci G, de Chiara A, Pinto A (2009) Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Cancer Chemother Pharmacol 64(5):907–916CrossRefGoogle Scholar
- 41.Mounier N, El Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas R-O et al (2013) Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial. Haematologica nov 98(11):1726–1731CrossRefGoogle Scholar
- 45.Stukov AN, Filatova LV, Latipova DK, Bespalov VG, Belyaeva OA, Kireeva GS et al (2015) Therapeutic activity of gemcitabine in intracranial tumors. Vopr Onkol 61(2):274–279Google Scholar