Clinical Factors and Transplantation Are Associated With PCL Prognosis

A retrospective cohort study of 153 patients with plasma cell leukemia (PCL), including the subtypes of primary PCL (pPCL) and secondary PCL (sPCL), has established the direction and significance of relationships between survival, patient characteristics, and treatment patterns, providing deeper insight into survival patterns and disparities.¹

A key finding of the study is that overall survival (OS) varied significantly by PCL subtype. Notably, patients with sPCL had a significantly shorter median OS (3.2 months) compared with patients with pPCL (36.6 months; P <.001).

Hematopoietic stem cell transplantation was also found to be associated with better survival outcomes. The median OS of those in the entire cohort who received transplants (48.7 months) was significantly higher than those who did not (5.9 months; P <.001). Among patients with pPCL, the median OS of those who received transplants (49.5 months) was significantly higher than those who did not (12.5 months; P <.001). Likewise, among patients with sPCL, the median OS of those who received transplants (16 months) was significantly higher than those who did not (3.4 months; P =.005). There was no indication of a survival benefit of initial allogeneic transplantation over autologous transplantation.

Regarding genetic characteristics, there were no significant differences observed in the frequency of high-risk genetic features and t(11;14). Additionally, while there was variation in treatment regimens by disease subtype, there were no significant differences in survival observed across the different modalities analyzed, including proteasome inhibitor (PI)-based triplet therapies and VTD-PACE-like (bortezomib-thalidomide-dexamethasone-cisplatin-doxorubicin-cyclophosphide-etoposide) regimens by subtype and across the entire cohort.

“This is, to the best of our knowledge, the largest multicenter study conducted in the US of this rare disease,” said the investigators, Singh et al, in the paper.¹

The objective of this study was to examine clinical and genetic patient characteristics, disease features, and treatment-associated survival outcomes across the entire cohort and stratified by disease subtype. The analytic sample consisted of 153 patients with PCL, including 96 patients with pPCL and 57 patients with sPCL, diagnosed between January 2010 and January 2021 at 7 academic centers in the United States.

What Are the Future Directions for PCL Treatment and Research?

As a rare, aggressive disease with no current standard-of-care treatment, PCL is characterized by short survival duration and high mortality rates, warranting the development of treatments that can prolong survival. The findings from this study highlight the survival disparities between those with pPCL and sPCL and the viability of transplantation as treatment option, which may help inform future treatment strategies.

Another retrospective cohort study published in Blood in 2024 led to similar takeaways.² Venkatesh et al concluded that stem cell transplant significantly improved OS in patients with pPCL, with double autologous tandem transplant providing additional survival benefits.

“One of the primary challenges in treating PCL is the limited data and lack of large, well-designed clinical trials,” noted the investigators in the Haemotologica paper. “The bulk of the literature has focused on pPCL, with comparatively fewer studies exploring the more aggressive sPCL type. The heterogeneity in clinical course and treatment responses between pPCL and sPCL further complicates the development of standardized treatment protocols.”

The investigators acknowledged various limitations of the study, including the retrospective design, missing data on key variables such as genetic features; first-line chemotherapy, and treatment response; and lack of a racially and ethnically diverse cohort. Looking ahead, they underscored the importance of additional prospective and experimental studies, studies that characterize sPCL risk factors to address determinants of disease progression, and a focus on developing novel therapeutics that can improve response rates, specifically in sPCL.

REFERENCES:

1. Singh S, Peshin S, Wertheim BC, et al. Outcomes and treatment patterns in primary and secondary plasma cell leukemia: insights from a large US cohort study. Haematologica. 2025;110(9). doi:10.3324/haematol.2024.287158

2. Venkatesh P, Mansour R, Ehsan H, et al. Optimal Treatment for Newly Diagnosed Primary Plasma Cell Leukemia: A Retrospective Multicenter Analysis. Blood. 2024; 144 (Supplement 1): 3317. doi: 10.1182/blood-2024-207270