Salvage therapy with bendamustine for methotrexate refractory recurrent primary CNS lymphoma: a retrospective case series
There is comparatively limited therapy for recurrent primary central nervous system lymphoma (PCNSL). Salvage therapies include re-challenge with high-dose methotrexate (HD-MTX), whole brain radiotherapy, temozolomide, topotecan and premetrexed. Bendamustine is a novel bifunctional alkylator with established activity in B cell systemic lymphomas but never previously evaluated in PCNSL. The objective of the current study was to assess response and toxicity of bendamustine in recurrent PCNSL following prior salvage therapy in a retrospective case series. Twelve adults [six males; six females: median age 59 years (range 43–74)] with HD-MTX refractory recurrent PCNSL were treated with bendamustine. All patients were treated at second recurrence following failure of prior salvage therapy. A cycle of bendamustine was defined as two consecutive days of treatment (100 mg/m2/day) administered once every 4 weeks (maximum number of cycles 6). Toxicities seen were Grade 2 (24 episodes in 10 patients) and 3 (10 episodes in 5 patients) only and included lymphopenia (8 patients), hyperglycemia (7 patients), fatigue (7 patients) and nausea (4 patients). The median number of cycles of therapy was 3.5 (range 1–6). Radiographic response was progressive disease in 5 (42 %), stable disease in 1 (8 %), partial response in 3 (25 %) and complete response in 3 (25 %). Median progression free survival (PFS) was 3.5 months (range 1–14 months) and 6-month PFS was 33 %. In this small retrospective series of select patients with recurrent PCNSL refractory to HD-MTX, bendamustine appears to have modest single agent activity with manageable toxicity. Confirmation in a larger series of similar patients is required.
KeywordsBendamustine Primary CNS lymphoma (PCNSL) High-dose methotrexate (HD-MTX) refractory
Marc C. Chamberlain collected and analyzed data. No personal communications cited in the manuscript.
Conflict of interest
The author reports no conflict of interest.
- 4.Colombat P, Lemevel A, Bertrand P et al (2006) High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of GOELAMS Group. Bone Marrow Transplant 38:417–420. doi: 10.1038/sj.bmt.1705452 PubMedCrossRefGoogle Scholar
- 5.Montemurro M, Kiefer T, Schuler F et al (2007) Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol 18:665–671. doi: 10.1093/annonc/mdl458 PubMedCrossRefGoogle Scholar
- 6.Illerhaus G, Muller F, Feuerhake F, Schafer AO, Ostertag C, Finke J (2008) High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica 93:147–148. doi: 10.3324/haematol.11771 PubMedCrossRefGoogle Scholar
- 12.Doolittle ND, Miner ME, Hall WA et al (2000) Safety and efficacy of a multicenter study using intra-arterial chemotherapy in conjunction with osmotic opening of the blood–brain barrier for the treatment of patients with malignant brain tumors. Cancer 88:637–647. doi: 10.1002/(SICI)1097-0142(20000201 PubMedCrossRefGoogle Scholar