This retrospective MSK study compared infectious complications among adults with relapsed/refractory multiple myeloma treated with B-cell maturation antigen (BCMA)-directed therapies, including CAR-T, bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs). Among 256 patients, 92 received CAR-T, 55 received BsAbs, and 109 received ADCs. Severe infections were more common with BsAbs than CAR-T: 40% of BsAb recipients had grade ≥3 infections compared with 26% of CAR-T recipients. CAR-T recipients had no grade 4 or 5 infections, while BsAb recipients experienced grade 4 infections in 4% and grade 5 infections in 7%. Severe infection risk was lowest in the ADC group, at 8%.

The study found that infection risk followed different patterns by treatment type. With CAR-T, the most first severe infections occurred within the first 100 days, while BsAb-related infection risk appeared more prolonged over the first year. Hypogammaglobulinemia was common after both CAR-T and BsAb therapy, but severe infections during hypogammaglobulinemic periods were more pronounced with BsAbs. Neutropenia was more common after CAR-T and associated with higher infection risk, supporting the need for close monitoring and supportive care. Overall, the authors conclude that BCMA-directed BsAbs may require especially vigilant infection prevention strategies, including consideration of immunoglobulin replacement during treatment-induced hypogammaglobulinemia. CAR-T and ADCs may require different supportive-care approaches.

Reference: Lesokhin A, Nath K, Shekarkhand T, et al. Comparison of Infectious Complications with BCMA-directed Therapies in Multiple Myeloma. Res Sq [Preprint]. 2024 Feb 7:rs.3.rs-3911922. doi: 10.21203/rs.3.rs-3911922/v1. Update in: Blood Cancer J. 2024 May 31;14(1):88. doi: 10.1038/s41408-024-01043-5. PMID: 38405866; PMCID: PMC10889082.

This review focuses on the differential diagnosis of multiple myeloma and other plasma cell neoplasms, especially conditions that can closely mimic them. It highlights two major diagnostic challenges: distinguishing plasmablastic/anaplastic plasmacytoma from plasmablastic lymphoma and separating true plasma cell neoplasms from low-grade B-cell lymphomas with plasmacytic differentiation. Because these entities can share overlapping morphology and immunophenotype, the authors emphasize the need to integrate clinical history, laboratory findings, morphology, flow cytometry, immunophenotype, cytogenetics, EBV status, and molecular sequencing to reach the correct diagnosis.

The review outlines key distinguishing features across several mimics, including lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, marginal zone lymphoma, CLL/SLL, follicular lymphoma, and mantle cell lymphoma with plasmacytic differentiation. It notes that B-cell lymphomas with plasmacytic differentiation often retain B-cell markers such as CD19 and CD45, while multiple myeloma plasma cells more often show aberrant loss of CD19/CD45 and expression of CD56. Molecular findings also can help, such as MYD88 mutations in lymphoplasmacytic lymphoma, MYC rearrangements in plasmablastic lymphoma, and MM-type translocations in plasma cell neoplasms. Overall, the article reinforces that accurate diagnosis depends on avoiding reliance on any single feature and instead using a comprehensive, context-driven workup.

Reference: Cantu MD, Chen W. Differential diagnosis of multiple myeloma. Semin Diagn Pathol. 2025;42(6):150944. doi: 10.1016/j.semdp.2025.150944. Epub 2025 Aug 7. PMID: 40813193.

This study evaluated whether readily available clinical and lab factors could predict “functional high-risk” (FHR) multiple myeloma-patients who relapse very early despite current therapies. Researchers retrospectively analyzed 1026 patients treated from 2019-2024 across 12 Italian hematology centers and defined FHR as progression-free survival (PFS) of ≤18 months for transplant-eligible patients or ≤12 months for non-transplant-eligible patients. Overall, 17% of patients met the FHR definition. These patients had dramatically worse outcomes, with median PFS of 7 months vs 57.5 months in non-FHR patients, and median overall survival of 19 months vs not reached in the non-FHR group.

The researchers built a practical risk model using ECOG performance status ≥2, ISS stage III, and a modified lab formula based on LDH, creatinine, hemoglobin, and platelet count. This score separated patients into low-, intermediate-, and high-risk groups, with FHR rates of 7%, 29.5%, and 63.5%, respectively, although the model’s AUC was modest at 65% and requires external validation. Importantly, frontline regimens containing anti-CD38 monoclonal antibodies were associated with significantly lower FHR frequency and longer PFS, especially in high-risk patients. The study concludes that simple, accessible clinical and laboratory markers may help identify patients at risk for early relapse when advanced cytogenetic or genomic data are unavailable. It also stresses that anti-CD38-based combinations may help reduce the likelihood of FHR disease.

Reference: Morè S, Offidani M, Corvatta L, et al. The strange case of functional high-risk multiple myeloma patients: is it possible to identify them in clinical practice? Cancers (Basel). 2025 Nov 6;17(21):3580. doi: 10.3390/cancers17213580. PMID: 41228371; PMCID: PMC12607954.