Study Examines Prognostic Subsets of B-Cell Receptor Immunoglobulins in CLL

A recent study evaluating the impact of stereotyped B-cell receptor immunoglobulins (BcR IG) on 4 relevant clinical outcomes found that subset #2 is an independent adverse-prognostic indicator irrespective of IG heavy variable (HV) mutational status in early and advanced stage chronic lymphocytic leukemia (CLL).

Almost one-third of all patients with CLL express stereotyped BcR IG and can be assigned to distinct subsets, each with a particular BcR IG.

The study investigated #1, #2, #4, and #8 stereotyped subsets which were associated with specific clinicobiological characteristics and outcomes in retrospective studies. The researchers evaluated the associations and prognostic value of the BcR IGs in prospective multicenter clinical trials that reflected early-stage patients as well as patients in need of treatment, enrolled in 3 phase 3 trials, and treated with different chemotherapy immunotherapies.

“Using the data of four prospective multicenter clinical trials of the German CLL study group (GCLLSG), the primary objective of the current study was to search for associations between the most common and best characterized CLL stereotyped subsets (#1, 2, 4 and 8) and disease characteristics as well as outcome and, moreover, compare these findings against non-subset U-CLL and M-CLL,” explained the authors. “The secondary objective was to study the prognostic value of subset #2 irrespective of its IGHV mutational status.”

The analysis revealed that subset #1 was associated with higher CLL international prognostic index scores and similar clinical course to CLL with unmutated IGHV genes in both early and advanced groups.

Additionally, the study reported that IGHV-mutated (M-CLL) subset #2 cases had shorter time-to-first-treatment (TTFT) compared to other M-CLL cases in the early-stage cohort. Subset #2 also had shorter time-to-next-treatment (TTNT) in the advanced-stage cohort.

“Taken together, we confirmed for the first time in prospective clinical trials that subset #2 is an independent prognostic marker for shorter TTFT, TTNT and PFS in CLL, regardless of the IGHV mutational status,” concluded the study. “Therefore, patients with CLL subset # 2 should be monitored closely. Thus, CLL clinical guidelines should include subset #2 also when mutated as an independent marker for high risk in patients receiving chemo-immunotherapy. Furthermore, our study showed that assignment to stereotyped subsets may have different impact depending on clinical stage in chemo-immunotherapy settings.”

The authors suggest that future studies must assess the relevance of the subset classification in regards to the response of novel therapies.

Reference

Jaramillo S, Agathangelidis A, Schneider C, et al. Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG) [published on December 26, 2019]. Haematologica. doi: 10.3324/haematol.2019.231027.