Navigating the Prognostic Complexity of IgH Cytogenetic Abnormalities in Multiple Myeloma Among Diverse IgH Cytogenetic Abnormalities–Involved High‐Risk Stratifications

To evaluate the clinical and prognostic significance of immunoglobulin heavy chain (IgH) cytogenetic abnormalities in patients with newly diagnosed multiple myeloma (NDMM) and explore their association with other high-risk cytogenetic features. We retrospectively analyzed 503 NDMM patients treated between February 1, 2016, and February 29, 2024. Cytogenetic abnormalities were identified by fluorescence in situ hybridization. The study uncovered a significant correlation between IgH cytogenetic abnormality and an increased prevalence of anemia (p < 0.001), thrombocytopenia (p = 0.005), and the presence of high-risk cytogenetic aberrations, including +1q21 (p < 0.001) and P53 deletion (p = 0.001). Patients afflicted with IgH cytogenetic abnormality were found to have more advanced stages of the disease, as indicated by higher Disease Stage (p < 0.001), International Staging System (p = 0.018), Revised International Staging System (RISS) (p < 0.001), and Second Revision of the International Staging System (p < 0.001). This cytogenetic abnormality was also linked to a markedly diminished progression-free survival (PFS) across RISS I-II, yet autologous stem cell transplantation (ASCT) offered significant improvement for PFS (p < 0.05). Notably, the specific t(14;16) and t(14; undefined) were significantly associated with shorter PFS (p < 0.001) and shorter overall survival (OS) (p < 0.05). Additionally, the confluence of IgH cytogenetic abnormality with other cytogenetic abnormalities, particularly +1q21, P53 deletion, RB/D13S319 deletion, and elevated LDH level, was found to exacerbate the disease outcome. IgH cytogenetic abnormalities indicate aggressive disease and poorer survival in NDMM, especially when accompanied by other high-risk markers. ASCT may mitigate these adverse outcomes, supporting its role in individualized treatment strategies.