Clinical Characteristics and Survival Outcomes of Patients with Primary and Secondary Plasma Cell Leukemia According to the 2021 Definition: A Single Center Retrospective Study
Authors: Shalaby Khalid , Azad Farhan , Parker Sarah , Wang Katy , Attwood Kristopher , Hillengass Jens 
Published: December 2024

Plasma Cell Leukemia (PCL) is a rare malignancy with poor overall survival (OS). In 2021, the International Myeloma Working Group revised its diagnostic criteria by lowering the threshold of circulating plasma cells (PC) required for diagnosis to be ≥5%. PCL is classified as primary PCL (pPCL) when patients have ≥5% circulating PCs at the time of diagnosis and as secondary PCL (sPCL) when patients with relapsed/refractory multiple myeloma (MM) have leukemic transformation with ≥5% circulating PCs.Between 2010 and 2024, all patients with PCL were identified in the MM database at a tertiary cancer center. The study protocol was reviewed and approved by the Institutional Review Board. Available clinical and laboratory data at baseline (i.e. new diagnosis for pPCL and time of transformation to sPCL) were collected. We evaluated response to induction regimens, impact of stem cell transplant (SCT), progression free survival (PFS) and OS. For sPCL, we identified prior lines of therapy, time from MM to sPCL, triple-class (PI, IMiD, Anti-CD38 mAb) refractory status, penta-class (2 PIs, 2 IMiDs, 1 Anti-CD38 mAb) refractory status, and Daratumumab (Dara)-refractory status at time of diagnosis.Patient demographic and clinical characteristics were summarized using the median and range for continuous variables, and frequencies and relative frequencies for categorical variables. Survival outcomes in months (m) were summarized using Kaplan-Meier curves, where estimates of the median were obtained with 95% confidence intervals and comparisons were made using the log-rank test. Associations between survival outcomes and baseline characteristics were evaluated using Cox regression models, from which hazard ratios (HR) and corresponding 95% confidence intervals (CI) were obtained. All analyses were performed in SAS v9.4 (Cary, NC) at a significance level of 0.05. We identified 59 patients with PCL; 30 had pPCL while 29 had sPCL. In the overall cohort, the median age was 66.8 years (range 25 - 85). Cytogenetics data were available for 48 (81.3%) patients. The majority of patients (60.4%) had high-risk and ultra-high-risk disease by Florescent In-Situ Hybridization (FISH). The most common FISH abnormality was Gain 1q21 (43.8%) followed by t(11;14) at 31.25%.In the sPCL cohort, 55.2% had prior SCT, 72.4% of patients had triple-class refractory disease and Dara-refractory disease, while 51.7% had penta-refractory disease. The median time from first diagnosis of MM to sPCL was 31.5 m (range 5.5-131). The median time to sPCL in patients who received Dara-containing regimens for MM was 46.8 m (range 10.3-56.6) compared with 12.3 m (range 5.6-17.3, P= 0.0067) in patients who didn't. Patients with sPCL had a median of 3 (range 1-11) prior lines of therapy.Of the whole cohort, 51.9% received an induction regimen with novel agents (PI, IMiD, Anti-CD38 mAb without chemotherapy). More patients with pPCL (48.3%) received SCT after PCL diagnosis compared with 10.3% of patients with sPCL. Of the evaluable patients with pPCL and sPCL, 82.1% (23/28) and 64.7% (11/17) achieved partial response or better respectively.Median PFS was significantly worse in patients with sPCL than pPCL (2.2 vs. 38.3 months; HR 0.16; 95% CI 0.07-0.35, P=&lt;0.001). Median OS was also significantly worse in patients with sPCL compared with pPCL (3.1 months vs. NR [not reached]; HR 0.09; 95%CI 0.04-0.23, P=&lt;0.001). At a median follow up of 18.3 months, the 1-year and 3-year OS in patients with pPCL were 76% (95% CI 57-87%) and 62% (95% CI 41-78%) respectively.The median post-SCT survival for patients with pPCL was NR compared with 6.7 months for patients with sPCL (HR 0.17; 95% CI 0.03-0.83, P=0.03). Dara refractory status was associated with worse OS (HR 5.63; 95% CI (2.75-11.51), P=&lt;.0001) even though triple and penta-refractory status were not. In the overall cohort, age, sex, FISH risk status, hemoglobin, calcium, and creatinine levels were not associated with a significant impact on OS. Platelet count ≥100,000/ml and bone marrow PC% ≥60% at the time of PCL diagnosis in the overall cohort were associated with better OS (HR 0.29; 95% CI 0.13-0.62, P=0.001 and HR 0.27; 95% CI 0.13-0.55, P=0.0004, respectively).PCL, particularly sPCL, remains an aggressive disease. We explored the role of novel agents, especially Dara, in the treatment of PCL. More prospective analyses and clinical trials are needed to deepen our understanding of PCL and improve its outcomes.