Integrated Immune Profiling Identifies Treatment-Associated Immune Patterns in Patients with B-Cell Hematological Malignancies

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Abstract Immune dysfunction in hematological malignancies arises from both disease-related alterations and therapeutic interventions, yet comprehensive approaches for characterizing the immune status remain limited. We evaluated an integrated immune profiling strategy combining antigen-specific serology and high-dimensional B-cell phenotyping. Thirty-eight patients with B-cell hematological malignancies receiving ibrutinib-, lenalidomide-, and rituximab-based therapies, or no treatment, were analyzed. Antigen-specific humoral responses were assessed by using a customized protein microarray containing 37 microbial antigens, enabling parallel IgG and IgM profiling. B-cell subpopulations were characterized by spectral flow cytometry. Multiomics factor analysis was applied to integrate serological and cellular data sets and identify major sources of immune variability. Distinct serological and cellular immune profiles were observed across therapeutic groups. Patients receiving ibrutinib displayed lower IgG levels against several microbial antigens and alterations in multiple B-cell compartments, whereas patients receiving lenalidomide-based therapy showed comparatively preserved B-cell populations and broader antigen-specific IgG reactivity. Rituximab-containing regimens were associated with marked reductions in several B-cell subsets. Integrated analysis identified cellular immune features as the major contributors to interpatient heterogeneity, which suggests the presence of treatment-associated immune patterns within the studied cohort. Therefore, integrated serological and cellular profiling provides a scalable framework for characterizing an immune fingerprint with potential prognostic value in patients with B-cell hematological malignancies. These findings support further investigation of immune monitoring approaches in larger longitudinal cohorts.