1221 - Occurrence and Evolution of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia Patients treated with Venetoclax: a study of the French Innovative Leukemia Organization (FILO).

Occurrence and Evolution of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia Patients treated with Venetoclax: a study of the French Innovative Leukemia Organization (FILO).

Introduction
Autoimmune cytopenias (AICs) are a common complication in chronic lymphocytic leukemia (CLL) occurring in about 5 to 15% of cases, however their impact on survival is still controversial. Some drugs like fludarabine or ibrutinib are known to trigger AICs, but there is poor evidence regarding the role of venetoclax (VEN) in those events. Some authors have reported successful treatment of AIC with VEN, while some cases of emerging AICs were reported in VEN associated trials. Furthermore, its frequent use with anti-CD20 agents might represent a confounding factor to assess its impact on AIC. Here we present the results of a multicenter study of the FILO aiming to evaluate the outcome of AICs in CLL patients treated with VEN.
Methods
We retrospectively collected in all the FILO centers the cases of CLL patients who presented any kind of AICs [autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenia (AIT), autoimmune erythroblastopenia (AIEB), aplastic anemia (AA) or autoimmune neutropenia (AIN)] before or after treatment with VEN. Regarding CLL response by itself, iwCLL criteria were used except for bone marrow biopsy criteria, then we defined CR as clinical CR. Regarding AICs, response criteria were used as already published (Michallet et al, Leuk Lymphoma 2011)
Results
Sixteen patients were included from 9 FILO centers in France. Twelve patients (75%) had background history of AICs before VEN initiation (see Table 1 for detailed characteristics). When starting VEN treatment, 13/16 (81%) had a progressive CLL (lymphocytosis or tumoral syndrome) and 12 out of 16 patients (75%) had an active AIC: 6 AIHA, 4 AIT, 1 Evans syndrome (ES) and 1 AIEB. Seven patients (58%) had rituximab in association to VEN. On VEN treatment, regarding AICs outcome, 8 patients achieved complete remission (CR) (67%, one patient had initial worsening of AIHA and then achieved CR), 2 partial response (17%) and 2 patients were in failure (17%). Regarding the CLL, 8 out of 12 achieved clinical CR (67%), 3 (25%) in PR and one (8%) in progression. There seemed to be a correlation between the response of the CLL and the AIC: all patients who achieve a CR of the CLL were also in CR regarding the AIC. In the same way, the 2 patients in failure regarding the AIC were in progression and PR of the CLL. Two patients in CR presented an occurrence of their AIC at 5months and 11 months after stopping VEN. The first one achieve CR once again at reintroduction of VEN.
Within the four patients (25%) who did not have an active AIC at the time of VEN, all developed AICs on VEN: 2 AIHA, 1AIT and 1 AIEB, at 2.9 months in median (1.9-4.3) after initiation of the treatment. Fifty percent of the patients had rituximab in association to VEN. VEN was definitely stopped for all 4 patients at D0 of the AIC for 2 patients, D1 and D38 for the 2 others.
Conclusion
VEN can be both the cause or the treatment of AICs associated with CLL. When introduced while an AIC is active, it results in CR of the AIC in a majority of the cases and seems to be correlated with the response of the CLL. It is more difficult to conclude about the AIC triggered by VEN in this retrospective setting, because VEN was stopped quasi immediately after AIC and never reintroduced.