Rituximab-Cyclophosphamide-Dexamethasone (RCD) Combination In the Management of Autoimmune Cytopenias Associated with Chronic Lymphocytic Leukaemia
Authors: Michallet Anne-Sophie , Rossignol Julien , Oberic Lucie , Picard Muriel , Garon Audrey , Willekens Christophe , Dulery Remy , Leleu Xavier , Cazin Bruno , Ysebaert Loic 
Published: October 2019

Abstract
Abstract 2451
Between 2003 and 2008, 48 CLL patients have received a treatment combining rituximab, cyclophosphamide and dexamethasone (RCD) for autoimmune disorders (AID). Diagnosis of AID was autoimmune haemolytic anemia (AHAI) in 26 (54%), autoimmune thrombocytopenic purpura (AITP) in 9 (18.8%), Evan's syndrome in 8 (16.7%) and pure red cell aplasia (PRCA) in 5 (10.5%). Median age of patients was 59 years (range 36–79) at diagnosis and 68 years (range 41–85 years) at AID, 81% of the population were males. Median interval between AID onset and CLL diagnosis was 60 months (range 0–240) and CLL was progressive in 40% of subjects at the time of AID. Concerning AID therapy, 81% of patients have received previously a median of 2 lines before RCD including prednisolone in 81%, splenectomy in 19% and rituximab in 23% of cases.
After RCD, we observed 89.5% of overall response whatever was the type of AID (19% of patients were treated in frontline). 83% of patients achieved a complete response: AHAI 81%, AITP 89%, Evans syndrome 75% and PRCA 100%. Median hemoglobin level and platelet count before RCD were 7.7 g/dl (range 3.8–10.1) and 36.5. 109/L (range 2–71) respectively. RCD was scheduled until achievement of a complete response and a median of 4 cycles were given (range 3–6). The median duration of response for AID was 24 months, but was significantly shorter for patients developing Evan's syndrome (p=0.005) and patients developing AID later during the course of CLL (>36 months, p=0.035). After RCD, we showed a significant correlation between AID relapse and relapse of CLL (p= 0.0001). Median time to CLL progression was 16 months but appeared significantly shorter for Evan's syndrome and AITP than for AHAI and PRCA (p=0.0001). Overall median survival for the entire cohort was 52 months. Median duration of the response was longer for patients presenting AID without CLL evolution particularly if these patients received RCD therapy early suggesting clearly that it is very important to control leukemic cells when treating AID. RCD was remarkably well tolerated even if older patients over 70 years: we did not observe any neutropenic fever and there were no dose reduction and no delay of the treatment. Nineteen of 48 patients (39.5%) experienced AID relapse (AIHA 23%, AITP 44.4%, Evan's syndrome 100% and PRCA 20%):. 8 patients received a second course of RCD and 7 (87.5%) obtained a second response. With a follow-up of 11 months, the duration of AID response from retreatment was 11 months after a second course of RCD compared to only 4 months if using other regimens (splenectomy or rituximab)(p=0.011).
In conclusion we demonstrated that RCD was efficient and very safe for the management of AID during CLLallowing steroid-sparing especially in elderly patients. The short duration of the response for patients presenting AITP and Evan's syndrome despite achievement of good clinical and biological responses after RCD argues to choose an other immunotherapy with an higher efficacy on the clonal B cells as RFC combination.

Disclosures:
Leleu: Celgene: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Leo Pharma: Consultancy; Amgen: Consultancy; Chugai: Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.