Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who had an MYD88 L265P mutation were uncommon and had distinct features, reported a cohort study in Blood Cancer Journal.

Study researchers identified 56 (3.1%) patients with CLL/SLL who had MYD88 mutations among 1779 who underwent mutational analysis. The study also included 100 patients who did not have MYD88 mutations to serve as a control group.

Among patients with MYD88 mutations, 38 (68%) had the L265P mutation and 18 (32%) had non-L265P mutations, which included 10 with V217F and 4 with M232T. Among the remaining patients with non-L265P mutations, 2 had a single-nucleotide mutation, 1 with S219C and the other with A6fs, and 2 had concurrent mutations, 1 with N291S/T294P and the other with F252I/M232T.

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No morphological differences were seen, as all patients had a typical CLL morphology. In general, patients with non-L265P mutations had similar features to patients with wild-type MYD88.

In contrast, patients with the L265P mutation had several unique features, in particular being younger (P =.0077) and having more favorable prognostic factors compared with patients who had wild-type MYD88.

Specifically, patients with the L265P mutation had lower levels of β2-microglobulin (P =.0173), a higher frequency of mutated IGHV (P <.0001) and isolated deletion of 13q14.3 (P=0.0036), less CD38 (P=0.0008) and ZAP-70 expression (P<0.0001), and a lower frequency of trisomy 12 (P =.0136), deletion in 11q22.3 (P =.041), NOTCH1 mutation (P =.0005), and SF3B1 mutation (P =.0033).

No clinical differences were seen, however, with all patients having a similar time to first treatment.

The study authors explained that evaluating prognosis was “challenging due to the low frequency of MYD88 mutations, the clinically indolent nature of CLL, and the presence of other confounding factors associated with prognosis.”

Shuai W, Lin P, Strati P, et al. Clinicopathological characterization of chronic lymphocytic leukemia with MYD88 mutations: L265P and non-L265P mutations are associated with different features. Blood Cancer J. 2020;10(8):86. doi:10.1038/s41408-020-00351-w