Relapsed Or Refractory Aggressive Non Hodgkin B-Cell Lymphomas Treated With Lenalidomide With/Without Rituximab Or Steroids: A Single Center Restrospective Study
Authors: Castellino Alessia , Chiappella Annalisa , Ghione Paola , Ceccarelli Manuela , Benevolo Giulia , Botto Barbara , Caracciolo Daniele , Ciochetto Chiara , Nicolosi Maura , Orsucci Lorella , Pecoraro Clara , Pregno Patrizia , Riccomagno Paola , Zanni Manuela , Ladetto Marco , Vitolo Umberto 
Published: October 2019

Abstract

Introduction
Patients with relapsed or refractory aggressive non Hodgkin B-cell lymphomas (NHL) not eligible to high dose chemotherapy and transplantation had a dismal prognosis. Lenalidomide showed activity in this setting as single agent or in combination. On this basis, we conducted a single center retrospective study to investigate efficacy and safety of lenalidomide alone or in association with rituximab or steroids in patients with heavily pretreated aggressive B-cell NHL.

Methods
Primary end points of the study were response rate (RR), defined as complete response (CR), partial response (PR) and stable disease (SD), and duration of response (DOR); secondary end points were feasibility and safety. Inclusion criteria for the analysis were: patients with relapsed/refractory aggressive B-cell NHL, aged >18 years, treated with lenalidomide between August 2007 to June 2012. Treatment scheme were: standard dose of oral lenalidomide 25 mg/day for 21 days every 28 days as single agent; standard dose of lenalidomide with the same schedule in association to weekly dexamethasone (20 mg bolus); lenalidomide 20 mg/day for 21 days every 28 days in combination with rituximab (375 mg/sqm) every 28 days. Patients were treated until disease progression or unacceptable toxicities.

Results
A total of 53 patients were analyzed. Different histotypes of NHL were included in the study: 34 diffuse large B-cell lymphomas (DLBCL), 11 mantle cell, 5 follicular, 2 primitive mediastinal B-cell and one Burkitt lymphoma. At relapsed before lenalidomide treatment, the majority of the patients presented an advanced disease: 40 (75%) stage 3-4; intermediate high/high risk international prognostic index (IPI) 23 (43%). Bone marrow was involved in 20 (38%) patients and 20 (38%) cases presented a bulky disease. Prior treatment lines were as follows: 8 (15%) patients received lenalidomide at first relapse while 24 (45%) underwent more than 3 previous lines of therapy; 14 (26%) patients received high dose chemotherapy and autologous stems cell transplant, one (2%) patient was allogenic transplanted and 4 (8%) did both before lenalidomide. All patients analyzed received lenalidomide: 31 patients (58%) underwent lenalidomide as single agent, 11 (21%) received a combination scheme of lenalidomide plus rituximab and 11 cases (21%) were treated with lenalidomide plus steroids. Median time from diagnosis and the beginning of lenalidomide was 25,3 months (3,7- 145,9), while median time from last previous therapy and lenalidomide treatment was 3,2 months (0,4- 38). At the time of this analysis response assessment was done in 51 patients: Response rate was 35% (18 patients), with CR 8 (15%), PR 5 (10%), SD 5 (10%). All patients who obtained CR underwent more than 3 courses of therapy, while among 31 patients who did not respond to treatment, 21 failures occurred during the first three cycles. Concerning different schemes of therapy: in the arm treated with lenalidomide as single agent RR was 24%, among patients underwent lenalidomide plus rituximab was 55% and in the group receiving lenalidomide plus steroid 45%. Among 34 DLBCL patients, RR was 41% (n= 14: CR 5, PR 4, SD 5), while in 11 patients affected by mantle cell lymphoma RR was 27% (n= 3: CR2, PR 1). Median DOR for all 18 responding patients was 12 months (0,2-24). At a median follow-up of 20 months, 5 patients were in stable CR, 7 continued lenalidomide, 11 relapsed and 28 died. Patients received a total of 257 cycles of lenalidomide, of which 25 were earlier interrupted and 48 were reduced in dose or duration; 50% of patients had at least one interruption in the planned treatment, however globally 91% of the expected dose was given. One patient died due to heart failure during the treatment. Toxicity was globally mild: most common grade 3-4 adverse events were neutropenia (19%), anemia (17%) and thrombocytopenia (17%). Five patients had grade 3-4 infections and 3 patients had thromboembolic events (only one grade 3). Two cases of neuropathies, both grade ≤ 2 were observed.

Conclusions
Lenalidomide single agent or in association with rituximab or steroids is effective and safe in patients with relapsed or refractory aggressive B-cell NHL, showing a promising response rate also in patients with heavily pretreated disease and with a mild toxicity profile.

Disclosures:
Vitolo: Roche: Speakers Bureau; Celgene: Speakers Bureau; Takeda: Speakers Bureau.