Bendamustine Treatment in Refractory or Relapsed T Cell Lymphomas: A Retrospective Multicenter Study
Authors: Reboursiere Emilie , Le Bras Fabien , Morschhauser Franck , Gyan Emmanuel , Clavert Aline , Malak Sandra , Sibon David , Damge Marion , Gardin Claude , Fornecker Luc-Matthieu , Garidi Reda , Tricot Sabine , Houot Roch , Joly Bertrand , Abarah Wajed , Choufi Bachra , Pham Anne-dominique , Chantepie Sylvain P , Fruchart Christophe , Gac Anne-Claire , Ollivier Catherine , Marin Emilie , Safar Violaine , Parcelier Anne , Maisonneuve Herve , Bachy Emmanuel , Cartron Guillaume , Jaccard Arnaud , Tournilhac Olivier , Rossi Cedric , Perrot Aurore , Martignoles Jean-Alain , Tilly Herve , Damaj Gandhi 
Published: October 2019

Abstract
Peripheral T-cell lymphoma (PTCL) is an aggressive disease with poor outcome. First line therapies are usually unsatisfactory with frequent need for second-line therapies. Median progression free survival (PFS) and overall survival (OS) for relapse PTCL patients are very short with few available therapeutic options. Bendamustine has been shown to be effective in this setting.
In order to assess the efficacy of bendamustine outside clinical trials, we conducted a national retrospective study of patients with the diagnosis of PTCL and who were treated with bendamustine. Between 2011 and 2013, about 200 patients with the diagnosis of PTCL have been treated in 27 centers with bendamustine. We present the results of 142 patients with complete clinical and biological data.
The population median age was 64y (range 28-89) with male/female sex ratio of 1,4 (83/59). Histologies were: angio-immunoblastic (AILT=63), PTCL-NOS (n=44), anaplasic-large (ALCL=13), NK/TCL (n=3), mycosis fungoides (MF=7), subcutaneous panniculitis-like-TCL (n=2), hepato-splenic-TCL (n=1) and others (n=9). The majority of patients (96%, n=130) had stage-disseminated disease and 72% (n=102) of them had extranodal localisations.
The median number of chemotherapy lines prior to bendamustine was 2 (range 0-8). Seven patients (5%) had received allogeneic stem cells transplantation (SCT) and 16 autologous SCT (11%) prior to bendamustine. The median duration of response (DoR) after the last prior to bendamustine chemotherapy was 4.3 months (range 1-70) and 50% of patients had refractory disease at bendamustine treatment.
Seventy-four patients (52%) received less than 3 cycles, mostly because of disease progression. Overall, they received a median of 2 cycles (range 1-8) with a median dose of 90mg/m2 (range 50-150).
The best overall response rate (ORR) was 32% (45/141) with complete response of 24% (CR=34). The median DoR was 3.3 months (1-39). For AITL patients, ORR was 52% (33/63) with CR of 41%, whereas it was 18% (8/44) with 11% of CR, in patients with PTCL-nos, respectively (p=0.01). Nine patients (6%) received allogeneic SCT in CR. Median PFS was 3 months (range 0.2-46.3) and median OS was 4.4 months (range 0.2-55.4). On multivariate analysis, chemotherapy refractory (p=0.001) patients' and extranodal disease localization (p=0.028) before bendamustine influenced adversely the ORR.
With a median follow up 4.4 months, 72% of patients (102/142) died. The most frequent cause of death were: disease progression (92%) or toxicities (6%). Grade 3-4 thrombocytopenia, neutropenia and infections were reported in 22%, 17% and 23% of cases, respectively.
Bendamustine as single agent must be considered as a therapeutic option for relapsed or refractory PTCL, particularly in patients with AITL. The safety profile was good. Combination of bendamustine with other drugs should be evaluated prospectively.

Disclosures
Off Label Use: Bendamustine, single molecule, alkylant agent with antimetabolite properties. Morschhauser:Genentech Inc./Roche: Other: Advisory boards. Cartron:Sanofi: Honoraria; GSK: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Roche: Consultancy, Honoraria.