Bendamustine Salvage Therapy for T-Cell Non Hodgkin Lymphoma

At present, the standard salvage treatment for relapsed/refractory (R/R) T-cell non Hodgkin lymphoma (NHL) has not been defined yet. Several studies indicated the high therapeutic activity and good safety profile of Bendamustine in B-cell NHL while, on the contrary, only few data are available in T-cell NHL. Recently, a multicenter phase II study showed that Bendamustine is active in angioimmunoblastic lymphoma and other T-cell NHL with 50% overall response rates (OR) and 28% complete responses (CR) (Gressin et al. J Clin Oncol, 2012 ASCO Annual Meeting Proceedings, 30, 15 suppl: 8026).

On this basis we evaluated in the contest of everyday clinical practice the efficacy and safety of Bendamustine salvage monotherapy in unselected adult patients with T-cell NHL.

Hematological and Oncological Italian centers involved in the treatment of patients with lymphomas were asked to report retrospectively the results of their experience regarding the use of Bendamustine in T-cell NHL. Response status and toxicity were evaluated according to Cheson 2007 and to the Common Terminology Criteria For Adverse Events V 4.0.

Clinical data of 20 patients with R/R T-cell NHL (median age 73 years, range 31–83; 14 males) treated with Bendamustine in seven Italian centers between March 2009 and June 2012 were analyzed. Investigated series included 6 peripheral T-NHL-NOS, 4 angioimmunoblastic (AILT), 3 prolymphocytic T-cell leukemia (PLL), 3 advanced- stage Mycosis Fungoides (MF)/Sezary Syndrome (SS), 2 large granular lymphocyte (LGL) NHL and 2 ATLL- like HLTV-1 negative NHL. The median interval from diagnosis to Bendamustine treatment was 18 months (range 1–74). Eleven patients received up to 2 previous lines of therapy, while 9 received more than 2, including CHOP or CHOP-like therapy (14 patients), Fludarabine or Pentostatine (5), Gemcitabine based therapy (7), Alemtuzumab (4), Romidepsin (1), allogeneic stem cell transplant (1). Nearly 70% of patients were refractory to the last previous chemotherapy. Bendamustine was given as monotherapy at a dosage of 60 and 70 mg/m² (7 patients) or 90–100 mg/m²(13) for a median number of 2.5 cycles (range 1–8) and a total number of 67 cycles. Response to Bendamustine was CR in 2 (10%) and PR in 8 (40%), with an ORR of 50%, including 3 PR in T-cell NHL/NOS, 1 CR in AILT, 3 PR in PLL, 1 PR in MF/SS, 1 CR and 1 PR in LGL NHL. The median period of observation was 6 months (range 1–18 months); 6- months estimated PFS, OS and response duration are 63%, 70% and 60%, respectively. Three patients in PR (2 PLL and 1 MF) progressed after 3, 4 and 7 months. Grade 3–4 neutropenia, thrombocytopenia and anemia were registered in 44%, 25% and 19% of cases. Three patients developed pneumonia (1 invasive aspergillosis) and 1 had septic shock; no grade 3–4 extra hematological toxicity was reported.

Bendamustine is a safe and active agent that desertes further investigation in patients with T-cell NHL. Combinations with other cytostatics or target therapy with potential synergistic effect should be assessed in future prospective trials.

Zaja:Mundipharma: Honoraria. Off Label Use: Bendamustine In T-NHL. Fanin:Mundipharma: Honoraria.