Optimal Treatment for Newly Diagnosed Primary Plasma Cell Leukemia: A Retrospective Multicenter Analysis
Authors: Venkatesh Priyanka , Mansour Razan , Ehsan Hamid , Ahmed Nausheen , Mushtaq Muhammad Umair , Abdallah Al-Ola , Atrash Shebli , Paul Barry 
Published: December 2024

Background: Primary plasma cell leukemia (pPCL) represents the most aggressive plasma cell dyscrasia and has distinct biologic and clinical features which differentiate it from multiple myeloma. The International Myeloma Working Group (IMWG) adopted a more inclusive diagnostic criteria in 2021, but still pPCL remains rare and is nearly always an exclusion criterion for clinical trials. Classically, the prognosis of pPCL has been poor, with OS &lt; 3 years. However, most published studies of pPCL represent small cohort and often don't include patients who meet criteria for pPCL based on the newer 2021 diagnostic guidelines. Given the limited data on appropriate treatment of pPCL we conducted a multi-center retrospective analysis of induction and consolidation regimens in pPCL patients with a goal of determining the optimum treatment for this condition.
Methods: Patients with newly diagnosed pPCL based on the 2021 IMWG guidelines (i.e. ≥5% circulating plasma cells) diagnosed prior to 12/31/23 at either Levine Cancer Institute or University of Kansas Medical Center and who received at least 1 cycle of induction therapy were included. Using R Core Team (2024) software, a descriptive analysis was performed. Continuous variables were summarized and reported the mean (min, max) and median (IQR). Dichotomized factors were summarized by total numbers and frequency. Fisher's exact was used to analyze contingency tables. Wilcoxon rank-sum test is used to compare two independent samples. Responses to therapy were evaluated using the International Myeloma Working Group (IMWG) criteria. Kaplan-Meier methods were used for progression-free (PFS) and overall survival (OS) calculations. A univariate/multivariate Cox proportional hazards analysis assessed the relationship between variables and a time-to-event outcome. The analysis calculates hazard ratios (HRs) and their associated confidence intervals (CIs) for each predictor variable, adjusting for censoring in survival data.
Results: A total of 56 patients were identified and included in our analysis. Median age at diagnosis was 63 (33-81); 35 patients (63%) were female, and 14 (25%) were African American. The majority of patients (54%) had high risk cytogenetics [defined as presence of del 17p, amplification (≥4 copies) of 1q, t(4;14), t(14;16), t(14;20), or complex cytogenetics]. Median circulating plasma cells at diagnosis was 34% (5-82). Notably, 13 (23%) of included patients has 5-19% circulating plasma and would not have met the prior definition for pPCL. Most (48%) patients received infusional chemotherapy with cisplatin, doxorubicin, cyclophosphamide, and etoposide (PACE) based induction regimens followed by cyclophosphamide, bortezomib, and dexamethasone (CyBorD- 25%) and lenalidomide, bortezomib, and dexamethasone (RVd-13%). Thirty-five (63%) patients underwent stem cell transplant. Of these, 20 had a single autologous transplant, and 15 underwent a tandem (7 auto-auto and 8 auto-allo). Overall response rate (ORR) was similar in patients after induction and transplant-in those patients who proceeded to transplant (75%; vs 80%), but depth of response (defined as a ≥VGPR) was significantly improved with transplant (53% vs 77%). Median OS was 22 months in the entire patient population; however, it was 9 months (95% CI 9; 27) in patients who did not proceed to transplant and was 46 month in patients who underwent any transplant (HR 0.30; 95% CI 0.16; 0.58). Median OS in patients who underwent any tandem transplant was 21 months, but was significantly improved for patients who had auto-auto tandem transplant (median OS 75 months; HR 0.05; 95% CI 0.0; 0.57).
Conclusions: Primary plasma cell leukemia remains a rare but aggressive form of plasma cell dyscrasia with limited data to guide treatment. Our dataset represents the largest cohort to date using the expanded definition of pPCL adopted by the IMWG in 2021. Our analysis shows that stem cell transplant significantly improves OS and that double autologous tandem transplant provides additional survival benefit. As many patients diagnosed with pPCL are ineligible for transplant based on end-organ damage from uncontrolled disease or disease that is refractory to induction therapy, more efforts are needed to diagnose and treat pPCL to allow patients to proceed to transplant.