To evaluate the clinical characteristics and their associations with treatment response and prognosis in multiple myeloma (MM) patients with positive autoantibody profiles (PA).

This single-center retrospective cohort study enrolled 189 MM patients who had undergone the autoantibody profile tests at the Gansu Provincial Clinical Medical Research Center for Molecular Diagnosis and Treatment of Hematological Diseases, the First Hospital, Lanzhou University, from April 2015 to April 2025. Follow-up data were collected until August 1, 2025. Based on the autoantibody profile results, patients were categorized into a negative autoantibody profiles group (NA) and a PA group for comparison of baseline characteristics and treatment responses between the two groups. The assessment of treatment response included the overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, non-response rate, and the utilization rates of key therapeutic strategies, such as anti-CD38 monoclonal antibody therapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Furthermore, the PA group patients were stratified into three subtypes based on antibody profiles: antinuclear antibody (ANA)-positive, anti-extractable nuclear antigen (ENA) antibody-positive, and antineutrophil cytoplasmic antibody (ANCA)-positive, to analyze prognostic differences. The Kaplan-Meier survival curve was used to calculate median survival time, and Cox regression analysis was performed to evaluate prognostic factors.

A total of 189 patients with MM were included, with 57 (30.16%) in the PA group and 132 (69.84%) in the NA group. All patients received treatment; 58 (30.69%) received anti-CD38 monoclonal antibody therapy, and 57 (30.16%) underwent auto-HSCT. After induction therapy, the ORR was 75.66% (143/189), comprising a PR in 43.39% (82/189) and a CR in 32.28% (61/189). The CR rate was significantly lower in the PA group than in the NA group (21.05% vs 37.12%, P=0.031). At a median follow-up of 39 months (IQR 16 to 59), the median progression-free survival (PFS) was 37 months (IQR 16 to 58) for the entire cohort, while the median overall survival (OS) was not reached. Kaplan-Meier analysis showed significantly shorter median PFS in the PA group versus the NA group (31 vs 43 months, P=0.048). Subgroup analysis based on specific autoantibodies revealed that patients with anti-ENA antibody positivity had significantly shorter median OS (41 vs 61 months, P=0.038) and PFS (28 vs 41 months, P=0.001) than those without. No significant differences in OS or PFS were observed between ANA/ANCA-positive and -negative groups. Cox regression identified anti-ENA antibody positivity (P=0.004) and male sex (P<0.001) as independent risk factors for OS, whereas achievement of CR post-induction (P=0.002) and anti-CD38 therapy (P=0.008) were protective factors. For PFS, independent risk factors were male sex (P<0.001) and anti-ENA positivity (P<0.001), with protective factors including elevated fibrinogen (P=0.011), achievement of CR (P=0.009), and anti-CD38 therapy (P=0.011).

MM patients with positive autoantibodies exhibit inferior responses to induction therapy and poor long-term outcomes. Anti-ENA antibody positivity is an independent risk factor for both OS and PFS in MM.