Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG)

• Published in: Haematologica (Roma) 2020-11, Vol.105 (11), p.2598-2607
• Main Authors: Jaramillo, Sonia, Agathangelidis, Andreas, Schneider, Christof, Bahlo, Jasmin, Robrecht, Sandra, Tausch, Eugen, Bloehdorn, Johannes, Hoechstetter, Manuela, Fischer, Kirsten, Eichhorst, Barbara, Goede, Valentin, Hallek, Michael, Döhner, Hartmut, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, Stilgenbauer, Stephan
• Format: Article
• Language: English
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2019.231027

Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each with a particular BcR IG. The largest stereotyped subsets are #1, #2, #4 and #8, associated with specific clinicobiological characteristics and outcomes in retrospective studies. We assessed the associations and prognostic value of these BcR IG in prospective multicenter clinical trials reflective of two different clinical situations: i) early-stage patients (watch-and-wait arm of the CLL1 trial) (n=592); ii) patients in need of treatment, enrolled in 3 phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1861). Subset #1 was associated with del(11q), higher CLL international prognostic index (CLL-IPI) scores and similar clinical course to CLL with unmutated immunoglobulin heavy variable (IGHV) genes (U-CLL) in both early and advanced stage groups. IGHV-mutated (M-CLL) subset #2 cases had shorter time-to-first-treatment (TTFT) versus other M-CLL cases in the early-stage cohort (HR: 4.2, CI: 2-8.6, p