B-cell receptor stereotyped subsets and outcome for patients with chronic lymphocytic leukemia in the HOVON 68 trial

Aim: We here assessed the impact of B-cell receptor stereotypy on progression-free survival (PFS) and overall survival in patients from the HOVON 68 trial.Methods: Based on IGHV mutational analyses from participating centers in Sweden, Norway, Finland, Denmark, Poland, and the Netherlands, B-cell receptor stereotyped subsets were assigned using the ARResT/AssignSubsets software. Analysis for recurrent mutations was performed by next-generation sequencing by a 454-base platform. All other clinical data were extracted from the HOVON database by November 2016.Results: In total, 178 out of 192 patients with sequences available were technically suitable for analysis. Thirty-eight patients (21%) were assigned to one of the 19 major subsets: Subset #2 (n = 12, 6.7%), Subset #8 (n = 7, 3.9%), Subset #6 (n = 6, 3.4%), and Subset #1 (n = 5, 2.8%). Other subsets found were: Subsets #3, #5, #31, and #64B. By November 2016, a PFS event had occurred for 150 patients (84%) and 79 patients (44%) had died. The median follow-up time for patients still alive was 78.9 months. Patients with UM-IGHV belonging to Subset #2 had significantly longer PFS than UM-IGHV 3-21-utilizing non-Subset #2 patients [UM-IGHV Subset #2 median PFS 61.3 months (n = 8) vs. UM-IGHV 3-21 non-Subset #2 median PFS 22.3 months (n = 6), P = 0.01]. Overall, no significant differences in PFS between groups were found for patients with M-IGHV.Conclusion: In the HOVON 68 trial. Subset #2 patients had a good treatment outcome comparable to the outcome for non-high-risk patients with chronic lymphocytic leukemia following fludarabine-cyclophosphamide-rituximab-based treatment

Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia

CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early' patients. For the 'early' patients, high sCD52 levels were associated with a significantly shorter time to first treatment. Regarding prognostic factors, no clear correlations with stage, IGHV, or beta-2-microglobulin were found; in a cox multivariate analysis of the 'early' patients, sCD52 and IGHV both had independent prognostic value. Following chemo-immunotherapy, sCD52 decreased in parallel with leukocytes while during ibrutinib treatment and ibrutinib-induced ymphocytosis, sCD52 decreased along with lymph node reductions. In vitro IgM stimulation of CLL cells led to increased sCD52 levels in the medium. Our findings indicate that sCD52 reflects disease activity and potentially treatment efficacy in CL

No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(Immuno)therapy

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