Survival outcomes and treatment patterns in primary and secondary plasma cell leukemia: A multicenter retrospective cohort study Free

Plasma Cell Leukemia (PCL) is a rare and highly aggressive plasma cell disorder, typically categorized into primary Plasma Cell Leukemia (pPCL) and secondary Plasma Cell Leukemia (sPCL). PCL patients present with more severe clinical symptoms and biological abnormalities. Due to its rarity and heterogeneity, there is currently no standard treatment protocol for this condition.

This retrospective study included 100 PCL patients (circulating plasma cells [CPCs] ≥5%) from five tertiary hospitals in China, enrolled between September 2012 and May 2025. Chi-square tests or Fisher's exact test were used for categorical variables, while continuous variables between groups were compared using the nonparametric Mann–Whitney U test. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards models.

Of the 100 patients, 52 (50.9%) were male, with a median age of 63 years (range, 17-86 years). The median percentage of CPCs was 27.7% (range, 5.0-94.6%). Among the cohort, 62 (62.0%) were pPCL and 38 (38.0%) were sPCL. Compared to pPCL patients, sPCL patients exhibited lower hemoglobin (65 vs. 82 g/L, P = 0.002), platelet counts (40 vs. 89 ×10^9/L, P < 0.001), and albumin levels (32.6 vs. 38.7 g/L, P = 0.015), while lactate dehydrogenase (LDH) levels were elevated (463 vs. 327 U/L, P = 0.027). Furthermore, a higher proportion of sPCL patients were classified as R-ISS stage III (62.3% vs. 49.7%, P = 0.014), although the proportion of high-risk cytogenetic abnormalities did not differ significantly (77.8% vs. 72.7%, P = 0.428).

In terms of treatment regimens, a higher proportion of pPCL patients (82.3%, 51/62) received a proteasome inhibitor-based triplet regimen compared to sPCL patients (28.9%, 11/38; P = 0.002). Conversely, a greater proportion of sPCL patients (34.2%, 13/38) received a daratumumab-based quadruplet regimen compared to pPCL patients (9.7%, 6/62; P < 0.001). Notably, 14.5% (9/62) of pPCL patients and 18.4% (7/38) of sPCL patients underwent CAR T-cell therapy. Hematopoietic stem cell transplantation (HSCT) was performed in 24.2% (15/62) of pPCL patients, with 60.0% (9/15) receiving autologous transplant and 40% (6/15) undergoing allogeneic transplant. None of the sPCL patients received HSCT. Clinically, sPCL patients had significantly lower hematologic response rates than pPCL patients, with a ≥ very good partial response (VGPR) rate of 8.0% versus 63.5% (P < 0.001).

During a median follow-up period of 10.6 months (range, 0.5-124.5 months), the median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 3.6 months (95% CI, 1.8-5.4 months) and 6.7 months (95% CI, 1.7-11.8 months), respectively, with 69.7% of patients having died during the study. pPCL patients exhibited longer median OS compared to sPCL patients (16.6 vs. 1.6 months, P < 0.001). Among pPCL patients, receiving HSCT significantly improved OS (33.0 vs. 9.5 months, P = 0.008), with no survival advantage between autologous and allogeneic transplants (38.3 vs. 34.8 months, P = 0.661). Treatment with proteasome inhibitor-based triplet or daratumumab-based quadruplet regimens showed no notable difference in survival outcomes within the entire cohort or across PCL subtypes. However, patients who underwent CAR T-cell therapy exhibited superior outcomes across both pPCL and sPCL groups. Multivariate analysis revealed that extramedullary disease (HR 4.504, P = 0.028), elevated LDH (HR 2.292, P = 0.019), and CAR T-cell therapy (HR 0.207, P = 0.036) were independently associated with OS in sPCL patients. Among pPCL patients, independent predictors of OS included HSCT (HR 0.344, P = 0.043), achieving at least a ≥VGPR (HR 0.307, P = 0.003), elevated LDH (HR 2.706, P = 0.022), and thrombocytopenia (HR 2.348, P = 0.032).

Despite the advent of novel therapies, the prognosis of PCL remains poor. pPCL patients generally have a better response to treatment than sPCL patients, and HSCT remains a key therapeutic option. CAR T-cell therapy may represent a promising treatment modality for PCL patients in the future.