First Line Treatment with Bendamustine in Selected Non Hodgkin's Lymphoma Patients: Prospective Experience in Tuscany Region
Authors: Rigacci Luigi , Puccini Benedetta , Della Seta Roberta , Capochiani Enrico , Iovino Lorenzo , Cencini Emanuele , Bernardeschi Paolo , Kovalchuk Sofia , Benelli Gemma , Birtolo Silvia , Petrini Mario , Fabbri Alberto , Bosi Alberto 
Published: October 2019

Abstract
Bendamustine was introduced in Italy from 2008 and it was used as salvage therapy in patients pretreated, particularly in indolent lymphomas. Before approval as first-line treatment by the National Health System, starting from 2011 and thanks to our regional regulation, was possible to use Bendamustine in first line therapy as ‘off-label’ drug.
The aim of this study was to collect all consecutive patients treated in first line with Bendamustine in 7 Tuscany centers.
From June 2011 to December 2012, 72 patients were prospectively included in the study. Diagnosis was: Lymphocytic lymphoma in 25 patients (34%), Follicular lymphoma in 18 (25%), Diffuse large B cell lymphoma in 11 (15%), Mantle cell lymphoma in 10 (14%),
Lymphoplasmocytic lymphoma in 5 (7%) and MALT in 3 (5%). Thirty-nine patients were treated with Bendamustine 90 mg/m2 for two days, 28 with 70 mg/m2 and 5 with 120 mg/m2. The analyzed population must be considered negatively selected as such was not proposed the standard therapy. Moreover the data coming from literature and the experience in pre-treated patients increased the interest of clinicians for this drug. In 14 patients Bendamustine was used alone, in 56 in combination with Rituximab or other drug. The overall median age was 69 years (range 45-89), in DLBCL was 81 years and 78 years in MCL. Considering the advanced age of this population we applied the geriatric score assessment and 25% of patients were unfit or frail. The median number of cycles performed was 4 (range 2 - 6).
All patients but 2 were evaluable for response, 35 obtained a complete remission, 27 a partial remission considering the intention to treat the overall response rate was 86%, stable disease in 2 patients, progressive disease in 6 patients and not evaluable in 2 patients. According to histotype to note that all but two indolent lymphoma obtained a response; in aggressive lymphomas 4/11 DLBCL and 5/9 MCL reached a complete remission but 4 DLBCL and 2 MCL experienced rapid progression of the disease. Treatment was well tolerated, we observed: grade 3-4 neutropenia in 18 patients, no grade 3-4 anemia or thrombocytopenia. According to extrahematological toxicity was reported only grade 3-4 infection in 3 patients no other grade 3-4 toxicities were reported. Skin rush grade 1 was reported in in 5 patients. No toxic deaths were observed. After a median follow-up of 18 months the overall survival was 83%; 10 patients died all due to progressive disease. Progression free survival, after a median observation period of 12 months, was 60%; sixty-two patients are alive, 31 in continuous complete remission, 3 relapsed and 28 with disease under control.
In conclusion in this ‘real life’ negatively selected population, the use of Bendamustine showed a very high response rate particularly in indolent lymphomas, promising results, also, are observed in aggressive lymphoma suggesting that this drug can be used with interesting result in elderly patients who can not receive the standard therapy.

Disclosures
No relevant conflicts of interest to declare.