Prognostic implications of measurable residual disease and autologous hematopoietic stem cell transplantation in primary plasma cell leukemia in the era of novel agents

Abstract Background:Primary plasma cell leukemia (pPCL) is the most aggressive malignancy of plasma cell neoplasms, with a median overall survival (OS) of 12-36 months. The most optimal treatment approaches and specific prognostic factors for pPCL have not yet been clearly defined, creating difficulties in clinical practice and patient management. While the clinical value of minimal residual disease (MRD) has been well established in multiple myeloma, there is a lack of data on MRD in patients with pPCL. Besides, the role of autologous hematopoietic stem cell transplantation (ASCT) in the era of novel agents requires reassessment. Methods:We retrospectively conducted a single-center cohort study of all adult patients with newly diagnosed pPCL at Beijing Chaoyang Hospital between 2017 and 2024. The status of MRD was assessed using next-generation flow cytometry on bone marrow aspirates with EuroFlow instrument settings. MRD negativity was defined as the absence of detectable abnormal plasma cells at a minimum sensitivity threshold of 10-5 in any assessment conducted during first-line treatment. Group comparisons of continuous variables were performed using Wilcoxon rank-sum tests and of categorical variables using the χ2 test or Fisher's exact test. Progression-free survival (PFS) and OS curves were plotted with the Kaplan–Meier method. A univariate/multivariate Cox regression analysis was conducted to identify survival predictors, reporting hazard ratios (HRs) along with their associated confidence intervals (CIs). We applied multiple imputation for handling missing data, and sensitivity analyses were performed in the 40 patients received MRD detection. Survival comparison between ASCT and non-ASCT groups was performed after propensity-score matching (PSM) based on ISS stage, age and response after induction therapy. A P-value < 0.05 (two-sided) was considered statistically significant for all comparisons. Statistical analyses were performed by R 4.4.1 and SPSS 26.0 software. Results:A total of 70 patients with newly diagnosed pPCL were included in the analysis. The median age at diagnosis was 59.5 (29-82) years. Among the patients, 46 (65.7%) had 5-20% CPCs, while 24 (34.3%) exhibited ≥20% CPCs. The median follow-up period was 11.3 (0.4 - 71.3) months. The median OS and PFS were 33.5 months (95% CI, 17.3–not reached) and 15.4 months (95% CI, 11.0–28.5), respectively. 50% (20/40) of patients who underwent MRD assessment achieved MRD negativity. MRD-negative was identified as an independent prognostic factor for both OS (HR, 0.24; 95% CI, 0.06-0.98; P = 0.047) and PFS (HR, 0.29; 95% CI, 0.11-0.77; P = 0.013), with significantly longer median PFS of 40.7 months and not reached OS. Among the 17 patients who had paired response pre-ASCT and 100 days post-ASCT, 13 patients experienced an increase in the depth of remission, with 12 patients achieving MRD-negative complete remission after ASCT. The holistic improvement in response translated to a significant increase in OS for the ASCT cohort of 19 patients compared to the other group (median OS:56.9 months vs. 16.7 months, P = 0.009). The Kaplan-Meier curve still demonstrated the survival benefit of ASCT after PSM (median OS: 56.9 months vs. 7.3 months, P < 0.001). Conclusion:Our findings first present that MRD negativity, as a marker of deeper treatment response, is an independent prognostic factor associated with improved survival outcomes in pPCL patients. Additionally, even in the era of new agents, ASCT can still deepen remission and provide survival benefits, making it a preferred therapeutic option for TE patients with pPCL. These results provide valuable evidence for risk stratification and future treatment strategies in pPCL.