2026-06-29 | CEACAM1 expression by immunohistochemistry in B-cell lymphomas and plasma cell myeloma.

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with limited curative treatment options. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) has recently been implicated in B-cell receptor signaling in MCL. We evaluated CEACAM1 expression by immunohistochemistry across MCL and other mature B-cell neoplasms, including small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). We retrospectively analyzed 164 lymphoma cases, 35 MM cases, and 2 plasmacytomas. CEACAM1 expression was assessed on tissue microarrays by immunohistochemistry and scored using a prespecified dichotomous cutoff. In DLBCL, CEACAM1 status was correlated with cell-of-origin classification and targeted mutational data. CEACAM1 was expressed in 27 of 30 MCL cases (90%), higher than in the other lymphoma subtypes combined (35%; P < .0001). Expression was also seen in SLL (20/30, 67%), MM (23/35, 66%), MZL (8/22, 36%), and DLBCL (19/82, 23%). In DLBCL, expression was more frequent in germinal center B-cell subtype than activated B-cell subtype cases (30% vs 13%; P = .023). Within sequenced DLBCL cases, CEACAM1 expression was associated with BCL2 and TNFRSF14 mutations. In MM, CEACAM1 expression was not significantly associated with recurrent cytogenetic abnormalities, although a nonsignificant trend toward higher expression in t(11;14) cases (75% vs 53%, Fisher exact P = .28). CEACAM1 is frequently expressed in MCL and in subsets of other mature B-cell neoplasms and MM. These findings support further investigation of CEACAM1 as a biologically relevant marker and potential therapeutic target in selected lymphoid malignancies.

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2026-06-02 | Obinutuzumab plus bendamustine as first-line therapy for indolent B-cell lymphomas: a prospective multicenter open-label study.

This study evaluated the efficacy and safety of obinutuzumab plus bendamustine (GB) as first-line treatment for indolent B-cell lymphomas. In this prospective, multicenter, single-arm trial (NCT06415708), adults with newly diagnosed indolent B-cell lymphomas-including follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), hairy cell leukemia variant (HCL-v), and unclassified B-cell lymphoproliferative disorder (BCLPD-U)-received six induction cycles of GB followed by 2 years of obinutuzumab maintenance in responders (⩾ partial response). The primary endpoint was overall response rate (ORR), whereas secondary endpoints included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Among 220 enrolled patients (149 with FL and 71 with non-FL), 210 completed ⩾ 3 treatment cycles. At a median follow-up of 13.1 months, ORRs in the different patient subgroups were 96.6% (FL), 100% (MZL, HCL-v), 92.9% (WM), and 88.9% (BCLPD-U). The median DOR was 16.7 months in the FL group and was not reached in the non-FL group. PFS and OS were not reached in any subgroup. The FL and non-FL groups had comparable ORRs (P = 0.435); however, the FL group showed a higher CRR (92.4% vs. 78.5%; P = 0.004) and shorter PFS (P = 0.020). Treatment-emergent adverse events occurred in 42 patients and were more frequent in the non-FL group than in the FL group (26.8% vs. 15.4%; P = 0.046), particularly infections (18.3% vs. 6.0%; P = 0.005). Overall, the GB regimen demonstrated high response rates and manageable safety in Chinese patients with indolent B-cell lymphoma.

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2026-05-27 | Integrated multi-omic profiling reveals two distinct splenic marginal zone lymphoma subgroups with prognostic relevance.

Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy with notable genetic, epigenetic, and clinical heterogeneity. This study utilized coding and non-coding sequencing (n=74), including whole-genome sequencing (WGS) on 24 paired tumour-normal samples, targeted sequencing (n=55) and DNA methylation in 126 cases to characterize the disease. From WGS, we identified recurrent, predominantly clonal, coding mutations in KLF2 (50%), KMT2D (25%) and NOTCH2 (25%), alongside rare mutations in FLNC (8%), novel mutations in FAM135B (17%) and non-coding mutational hotspots in BCL6, PAX5 and BACH2, linked to aberrant somatic hypermutation. At least one non-coding hotspot was detected in 69% of cases. Copy-number aberrations (CNAs) were present in 73% of cases, including del(7q) (27%), gain(3q) (17%) and trisomy 12 (13%). DNA methylation profiling revealed two epigenetic subgroups: SMZL-HR (high-risk, n=67) and SMZL-LR (low-risk, n=59). SMZL-HR was associated with adverse features such as female sex, IGHV1-2*04 usage, KLF2 mutations, del(7q), shorter telomeres, and elevated epiCMIT scores. Transcriptomic analysis highlighted enhanced cell proliferation in SMZL-HR, with enrichment of E2F and G2M checkpoint pathways and epigenetic regulation via EZH2. SMZL-HR patients had significantly shorter time to first treatment (TTFT) (HR: 1.9, p=.003) and reduced overall survival (HR: 2.5, p=.039): 85% of SMZL-HR patients required treatment and showed a higher frequency of transformation (p=.007) and mortality (p<.001). Multivariate analysis confirmed SMZL-HR as an independent predictor of shorter TTFT (HR: 2.4, p=.001). These findings demonstrate the role of DNA methylation and molecular profiling in SMZL risk stratification.

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