Pb1957: prognostic significance of chronic lymphocytic leukemia with ighv-u in the era of novel agnets; real-life data

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia accounting for 25-30% of all the leukemias. It originates from a mature B cell with either mutated or unmutated immunoglobulin heavy chain variable region (IGHV) transcripts. A better understanding of the molecular basis and IGHV mutations status of CLL allows targeted therapies as a treatment options. Aims: We aim to present real-life data emphasizing the clinical features of our patients with immunoglobulin heavy chain variable region unmutated (IGHV -U) Methods: This multi-center, retrospective study included CLL patients with known IGHV mutational status. Ninety patients with available clinical data out of 114 patients who had IGHV mutation outcomes were included in our study. We evaluated IGHV mutation status by RNA-seq providing high resolution and high dynamic range transcription data. Results: The median age of the patients was 61 years(29-84), and 64.4% were male (Table 1). Forty-t wo patients (46.7%) had IGHV-U and 8 patients (8.9%) had both IGHV unmutated disease and 17p del. Fifty one patients 51 (56.7%) were treated during follow-up. Thirty-six percent of the patients received chemoimmunotherapy consisting of fludarabine, cyclophosphamide plus rituximab (FCR), or bendamustine plus rituximab (BR); 10% received chlorambucil in combination with anti CD20 antibodies or monotherapy; and 31% received Bruton’s tyrosine kinase inhibitor or B-cell lymphoma-2 (BCL-2) inhibitor with anti CD20 antibodies. In the treatment group 76.2 % IGHV unmutated disease and 62.5% of these patients were treated with novel agents. Median follow up time was 30.5 months (1-48). Median overall survival was 95.9% at 36 month in the cohort. Three-years OS for IGHV-M and IGHV-U was approximately 92.3 % and 100 %, respectively (p>0.5) (Figure1). No significant survival difference was detected in both groups during 36-months follow-up period.Summary/Conclusion: There were no difference in survival of patients with or without IGHV mutations. Our real life data suggested novel agents targeting B-cell receptor (BCR) pathway kinases or BCL-2 inhibitors can overcome the poor prognosis associated with unmutated IGHV status. Keywords: Immunoglobulin gene, Chronic lymphocytic leukemia