Rituximab For Hairy-Cell Leukemia (HCL): A Multicentric Retrospective Study Of 41 Cases
Authors: Leclerc Mathieu , Suarez Felipe , Noël Marie-Pierre , Vekhoff Anne , Troussard Xavier , Claisse Jean-François , Thieblemont Catherine , Maloisel Frédéric , Beguin Yves , Tamburini Jérôme , Barbe Coralie , Delmer Alain 
Published: October 2019

Abstract

Introduction
the purine analogs (PA) cladribine (CDA) and pentostatin have dramatically improved the prognosis of HCL and are considered the standard of care both in front-line therapy and at relapse. However, some patients still fail to respond or will eventually relapse after treatment with PA. Chimeric anti-CD20 monoclonal antibody rituximab has shown significant activity in HCL and is an option for relapsed/refractory patients either alone or in combination with PA.

Methods
we retrospectively reviewed 49 treatments with rituximab for classical HCL, undertaken in 41 patients (pts) from 10 centers in France and Belgium between july 2002 and september 2012. Patients were included if they had received at least 3 infusions of rituximab. Eight pts were treated twice with rituximab. Complete hematologic response (CHR) was defined as recovery of normal blood counts (without circulating HCL cells) and absence of HCL-related symptoms. CHR was further divided into 3 groups: (i) stringent complete response (sCR), if bone marrow evaluation was normal; (ii) unconfirmed complete response (uCR), if bone marrow evaluation was not done and (iii) CHR with persistent medullar infiltration (iCHR). Partial response (PR) corresponded to a ≥ 50% improvement for every CHR-defining criterion or normalization of at least one blood count, without circulating HCL cells.

Results
characteristics of pts before treatment are summarized in table 1. Rituximab was given as front-line therapy in 8 cases (16.3%). When used at relapse/progression, the median number of previous lines was 3 (range 1-8) and all pts had already received PA (both CDA and pentostatin in one third of them). Rituximab was given alone in 55% of cases, while it was combined with a PA in the 45% remaining cases, mostly CDA (18 of 22 cases). The median number of infusions was 4 (3-12). After treatment, median absolute neutrophil count (ANC), hemoglobin (Hb) level and platelet count were 2.75 x 109/L, 135 g/L and 180 x 109/L respectively. Persistent significant neutropenia (ANC < 1 x 109/L) and anemia (Hb < 100g/L) were each found in only 2 cases and 10.6% of patients had platelets < 100 x 109/L. Overall response rate (ORR) was 89.6% with 70.8% CHR including 6 sCR (12.5%), 26 uCR (54.2%) and 2 iCHR (4.2%). PR was achieved in 9 cases (18.8%) and 5 pts were non responders (10.4%). All the 8 pts who received rituximab as front-line therapy (along with CDA in 5 of them) achieved CHR. In the relapsed pts, ORR was 87.5% (including 65% CHR) with a better outcome for those having received both rituximab and PA (100% ORR including 85.7% CHR versus 79.2% ORR and 54.2% CHR after rituximab alone). The 5 pts who failed to respond were relapsed pts treated with rituximab alone. Interestingly, all the 8 pts who were re-challenged with rituximab responded again to treatment (6 uCR, 1 iCHR and 1 PR). Multivariate analysis identified 3 independent prognostic factors for response to rituximab: absence of previous therapy (OR=0.027 [0,001-0,555], p=0,0192), combination therapy (OR=10,120 [1,227-83,485], p=0,0316) and ANC before treatment (OR=1,002 [1,001-1,004], p=0,006). The median follow-up is 36 months (4-117). Relapse or progression was observed in 15 cases (34.1%), with a median time to relapse of 19 months (2-39). Relapse rate was higher (54.5%) and time to relapse shorter (17.5 months) when rituximab was administered alone, as compared to combination therapy with a PA (10% and 38.5 months respectively). Overall, 3-year relapse-free survival is 68.3%. Six pts have died and 3-year overall survival is 90.3%.

Conclusion
this study confirms the efficacy of rituximab in HCL patients, mostly when combined to PA. Nevertheless, the relapse rate is high and time to relapse short when rituximab is used as monotherapy beyond front-line treatment. Further prospective studies are warranted to confirm the superiority of the combination PA + rituximab over PA alone.

Disclosures:
Off Label Use: Rituximab for the treatment of hairy-cell leukemia.