PF491 COLD AGGLUTININ DISEASE: A RETROSPECTIVE ANALYSIS OF 95 CASES
Authors: P. Daufresne, C. Orvain, B. Mahe, A.‐V. Doncker, E. Gyan, M. Hamidou, P. Godmer, R. Houot, M. Bernard, V. Launay, A. Trebouet, R. Le Calloch, I. Grulois, G. Guillerm, T. Lamy
Journal: HemaSphere (2019)

Background: Cold agglutinin disease (CAD) is classified as primary or secondary to B or T‐cell lymphoma, auto‐immune disorders or cancers. Few studies have tried to determine which clinical and/or biological parameters may affect response to treatment and survival. Aims: We report on a large series of CAD cases and describe clinical characteristics, outcome, and prognostic factors. Methods: All cases of primary and secondary CAD treated between 2004 and 2017 in 15 French public hospitals were included in this study. All clinical and biological data were completed and centralized. We used multivariate Cox model to analyze overall survival and progression‐free survival. Results: Ninety‐five patients were included, 36 male and 59 female. Median age at diagnosis was 72 years. We identified 65 and 30 primary and secondary CAD, respectively. Causes of secondary CAD were as followed: B‐cell lymphoma (n = 25), T‐cell lymphoma (n = 3), auto‐immune disorder (n = 2). Thirty percent of patients had clinical symptoms at diagnosis (cold symptoms, anemia‐induced symptoms). Mean hemoglobin rate at diagnosis was 93 ± 22 g/L. Monoclonal immunoglobulin was found in 49% of cases. Mean LDH and reticulocytes were 606.5 ± 364.1 UI/L and 140.8 ± 79.9 G/L, respectively. Haptoglobin was below the normal value (0.3 g/L) in 66 patients (70%) and C3d direct antiglobulin test was found positive in all cases. A monoclonal IgM was detected in 46 patients (49%), with a mean peak at 3.9 ± 7.3 g/L. Bone marrow biopsy was available for 45 patients and twenty‐nine patients had primary CAD whereas sixteen had secondary CAD. Median time of follow‐up was 4.3 years. Overall response rate (ORR) to first line therapy was 76%: according to the different lines of treatment, ORR was 86% for patients treated with Rituximab monotherapy (group 1, n = 38),83% for Rituximab combined chemotherapy (group 2, n = 11: (RCD; n = 8), (RCHOP; n = 3), RCHOEP; n = 1), (R‐Bendamustin, n = 1) and 60% for other treatment such as steroids (group 3, n = 15). Median response duration was 19.2, 19.0 and 45.4 months for each group, respectively. Recurrence of CAD was observed in 34 cases. Twenty‐eight patients received a second‐line therapy. Overall response rate following second line therapy was 64%, 78% (Rituximab alone, n = 9), 60% (Rituximab combined chemotherapy, n = 10) and 67% (other treatment, n = 9), respectively. Twenty‐three patients died. Cause of death was hemolysis (n = 5), other cancers (n = 5) infectious disease (n = 2), other causes (n = 3), unknown (n = 8). Thirteen patients had grade 2 to 4 infections during CAD history. Median progression‐free and overall survival were 6.2 and 9.6 years, respectively. Both age and presence of adenopathy or splenomegaly at diagnosis were significantly associated with progression‐free survival. Only age at diagnosis was significantly associated with overall survival. Summary/Conclusion: We confirm that CAD is an indolent disease. Immunotherapy or immunochemotherapy is highly efficient but must be cautiously used regarding the high risk of infection.