Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study.
Caroline Houillier, Hervé Ghesquières, Cécile Chabrot, Carole Soussain, Guido Ahle, Sylvain Choquet, Emmanuelle Nicolas-Virelizier, Jacques-Olivier Bay, Jacques Vargaftig, Claude Gaultier, Valérie Touitou, Nadine Martin-Duverneuil, Nathalie Cassoux, Magali Le Garff-Tavernier, Myrto Costopoulos, Pierre Faurie, Khê Hoang-Xuan
Author Information
Caroline Houillier: Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, APHP, Sorbonne Universités UPMC Universités Paris VI, IHU, ICM, 47-83 boulevard de l'Hôpital, 75651, Paris Cedex 13, France. caroline.houillier@aphp.fr. ORCID
Hervé Ghesquières: Service d'hématologie, Centre Léon Bérard, 28 rue Laennec, 69008, Lyon, France.
Cécile Chabrot: Service d'hématologie, CHU Estaing, 1 place Lucie et Raymond Aubrac, 63100, Clermont-Ferrand, France.
Carole Soussain: Service d'hématologie, Hôpital René Huguenin-Institut Curie, 35 rue Dailly, 92210, Saint Cloud, France.
Guido Ahle: Service de neurologie, Hôpitaux Civils de Colmar, 39 avenue de la Liberté, 68024, Colmar Cedex, France.
Sylvain Choquet: Service d'hématologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
Emmanuelle Nicolas-Virelizier: Service d'hématologie, Centre Léon Bérard, 28 rue Laennec, 69008, Lyon, France.
Jacques-Olivier Bay: Service d'hématologie, CHU Estaing, 1 place Lucie et Raymond Aubrac, 63100, Clermont-Ferrand, France.
Jacques Vargaftig: Service d'hématologie, Hôpital René Huguenin-Institut Curie, 35 rue Dailly, 92210, Saint Cloud, France.
Claude Gaultier: Service de neurologie, Hôpitaux Civils de Colmar, 39 avenue de la Liberté, 68024, Colmar Cedex, France.
Valérie Touitou: Service d'ophtalmologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
Nadine Martin-Duverneuil: Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
Nathalie Cassoux: Service d'ophtalmologie, Institut Curie, Université Paris V, 26 rue d'Ulm, 75005, Paris, France.
Magali Le Garff-Tavernier: Service d'hématologie biologique, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
Myrto Costopoulos: Service d'hématologie biologique, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
Pierre Faurie: Service d'hématologie, Centre Léon Bérard, 28 rue Laennec, 69008, Lyon, France.
Khê Hoang-Xuan: Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, APHP, Sorbonne Universités UPMC Universités Paris VI, IHU, ICM, 47-83 boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m D1-2). Addition of rituximab (375 mg/m D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.
