Observation as the initial management strategy in patients with mantle cell lymphoma.

BACKGROUND: Patients with mantle cell lymphoma (MCL) follow a heterogeneous clinical course. While they generally require treatment initiation shortly after diagnosis, it is unclear whether deferring treatment in selected patients with an indolent clinical behavior affects their overall outcome. PATIENTS AND METHODS: In this population-based study, all patients diagnosed with MCL during 1998-2014 were identified in the British Columbia Cancer Agency Lymphoid Cancer Database. The associations between clinico-pathologic characteristics, including the expression of Ki67, SOX11, and TP53, and time to treatment (TtT) and OS were analyzed. RESULTS: A total of 440 patients with MCL were evaluated: 365 (83%) received early treatment and 75 (17%) were observed ≥3 months. In the observation group, 54 (72%) patients had a nodal presentation, 16 (21%) a non-nodal presentation, and 5 (7%) had only gastrointestinal involvement. Characteristics associated with deferred treatment included good performance status, no B symptoms, low LDH, non-bulky disease, non-blastoid morphology, and lower Ki67 values. The median TtT in the observation group was 35 months (range 5-79), and 60 (80%) patients were observed beyond 12 months. The median OS was significantly longer in the observation group than in the early treatment group (72 versus 52.5 months, respectively, P = 0.041). In multivariable analysis, treatment decision was not associated with OS [HR 0.804 (95% CI 0.529-1.221), P = 0.306]. CONCLUSIONS: A subgroup of patients with MCL may be safely observed from diagnosis without negatively impacting their outcomes, including patients with non-nodal presentation as well as asymptomatic patients with low burden nodal presentation and a low proliferative rate.

BCL2 mutations in diffuse large B-cell lymphoma.

BCL2 is deregulated in diffuse large B-cell lymphoma (DLBCL) by the t(14;18) translocation, gene amplification and/or nuclear factor-κB signaling. RNA-seq data have recently shown that BCL2 is the most highly mutated gene in germinal center B-cell (GCB) DLBCL. We have sequenced BCL2 in 298 primary DLBCL biopsies, 131 additional non-Hodgkin lymphoma biopsies, 24 DLBCL cell lines and 51 germline DNAs. We found frequent BCL2 mutations in follicular lymphoma (FL) and GCB DLBCL, but low levels of BCL2 mutations in activated B-cell DLBCL, mantle cell lymphoma, small lymphocytic leukemia and peripheral T-cell lymphoma. We found no BCL2 mutations in GC centroblasts. Many mutations were non-synonymous; they were preferentially located in the flexible loop domain, with few in BCL2-homology domains. An elevated transition/transversions ratio supports that the mutations result from somatic hypermutation. BCL2 translocations correlate with, and are likely important in acquisition of, additional BCL2 mutations in GCB DLBCL and FL. DLBCL mutations were not independently associated with survival. Although previous studies of BCL2 mutations in FL have reported mutations to result in pseudo-negative BCL2 protein expression, we find this rare in de-novo DLBCL.