The prognostic factors and immune microenvironment of primary plasma cell leukemia: the KMMWP-2204 study

Primary plasma cell leukemia (pPCL) is a rare but highly aggressive plasma cell malignancy with a dismal prognosis. We retrospectively analyzed the KMMWP-2204 cohort of 127 patients with newly diagnosed pPCL from 20 Korean centers to identify prognostic factors and assess treatment outcomes, and integrated these findings with exploratory single-cell RNA sequencing (scRNA-seq) data from bone marrow samples obtained from 4 patients with pPCL, 2 with multiple myeloma, and 3 healthy donors. Our findings support the revised 2021 International Myeloma Working Group 5% circulating plasma cell (CPC) diagnostic threshold, as patients with 5-19% and ≥20% CPCs had comparable survival despite differences in disease burden. Poor performance status (odds ratio [OR], 3.28; P=0.031), elevated lactate dehydrogenase (OR, 3.45; P=0.019) and del(17p) (OR, 3.58; P=0.025) independently predicted 6-month early mortality. Achievement of complete remission was the strongest predictor of improved survival (hazard ratio for overall survival, 0.30; P=0.005), whereas autologous stem cell transplantation (ASCT) appeared to have a consolidative rather than independent effect in time-dependent analyses. Although the use of intensive triplet or quadruplet induction regimens and ASCT increased in the post-2016 era, survival outcomes remained broadly similar across eras, likely reflecting differences in baseline risk and the retrospective nature of the cohort rather than regimen-specific efficacy. Exploratory scRNA-seq analysis identified transcriptional features suggestive of altered immune differentiation and myeloid-associated immunoregulatory signaling in pPCL, providing preliminary biological context for the observed clinical aggressiveness. These findings should be interpreted as hypothesis-generating and require validation in larger cohorts with orthogonal functional studies.