1104 - Non-Hematological Autoimmune Disorders are frequent in CLL, but are they clinically related? Data from a Single-center Real-Life Cohort

Background: Chronic lymphocytic leukemia (CLL) is marked by severe immune dysfunction, which results in an increased risk of autoimmune disorders (AID). The association of autoimmune cytopenia (AIC) with CLL has been extensively studied. However, there is little information about its relationship with other non-hematologic autoimmune complications.

Aims: To describe the prevalence and characteristics of patients with CLL spectrum (CLL, small lymphocytic lymphoma, and monoclonal B-cell lymphocytosis) and non-hematologic AID. The secondary objective was to ascertain differences in clinical and prognostic features between AIC and non-hematologic AID groups.

Methods: We included 712 patients with CLL from the historical database of our center. The medical records were retrospectively reviewed to identify any AID diagnosis. AID were categorized based on the American Autoimmune Related Diseases Association classification. Those patients with both AIC and non-hematologic AID were included into the AIC group.

Results: The main characteristics of patients with CLL and AID are shown in Table 1. After a median follow-up of 6.4 years (0.1-36.4), 87/712 (12.2%) presented non-hematologic AID, and 45/712 (6.3%) showed AIC; 11/712 (1.5%) had both AIC and a non-hematologic AID. In the non-hematologic AID group, endocrine disorders were the most frequent (48.3%; 42/87), followed by dermatological AID (33.3%; 29/87; including 5 patients with paraneoplastic pemphigus), and other AID such as rheumatoid arthritis (6.9%; 6/87), vasculitis (5.7%; 5/87), and neuromuscular syndromes (6.9%; 6/87). As diseases, the most observed non-hematologic AID were autoimmune hypothyroidism (n=41), psoriasis (n=17), rheumatic polymyalgia (n=7), rheumatoid arthritis (n=6), and pemphigus (n=5). Most patients (51/87; 58.6%) presented the non-hematologic AID before CLL diagnosis, with a median time of - 1.3 years (-45.8 – 15.9).

We found a significant association between AIC and the presence of poor biological variables (e.g., unmutated IGHV), and anti-CLL therapy. In contrast, female gender was the only variable significantly associated with non-hematologic AID. Prognostically, patients with CLL and AIC had shorter OS than those with non-hematologic AID (median 10.9 vs. 13.9 years; p=0.002) (Figure 1).

Summary/

Conclusion:
In our series, 12.2% of patients with CLL presented non-hematologic AID, the endocrine disorders being the most frequent. The presence of non-hematologic AID was not associated with CLL adverse features and these patients had the same prognosis as those with CLL without autoimmunity. In contrast, AIC was linked to the presence of poor biological features and had a negative impact on patients’ outcomes. Moreover. non-hematologic autoimmune disorders do not appear to be more frequent in CLL than in the general population, albeit the challenges they can pose in the management of patients with CLL should not be dismissed.