Evaluation of Characteristics and Outcomes of Patients with Primary and Secondary Plasma Cell Leukemia Treated with Modern Therapies
Authors: Broughton Megan , Bhatta Subodh , Sharma Nidhi , Umyarova Elvira , Khan Abdullah Mohammad , Devarakonda Srinivas , Bumma Naresh , Rosko Ashley , Benson Don , Cottini Francesca 
Published: December 2024

Background: Plasma cell dyscrasias are clonal proliferation of plasma cells (PC), resulting in a spectrum of clinical conditions, ranging from the asymptomatic presence of a monoclonal protein in the blood to symptomatic disease with organ damage. Usually, multiple myeloma (MM) cells remain in the bone marrow (BM) and rely on the support of the BM to survive. However, MM cells can also become independent from the BM, leading to systemic dissemination. These more aggressive forms of plasma cell dyscrasias are called plasma cell leukemias (PCL). PCL is referred to as ‘primary’ when the leukemic phase presents at diagnosis (pPCL), or ‘secondary’ when leukemic progression occurs in the context of preexisting MM (sPCL). In this abstract, we analyze the differences between pPCL and sPCL, investigating prognostic factors, immunophenotypes, therapeutic trends, and outcomes.

Methods: Medical records of all adult patients seen at our center between January 2010 and November 2023 with a diagnosis of PCL were reviewed, after approval from the Ohio State University Institutional Review Board. PCL was defined as the presence of plasma cell ≥5% of the peripheral total white blood cell count or an absolute plasma cell count of ≥2 × 109/L. We assessed disease characteristics, treatment types, and prognostic outcomes. Kaplan-Meier method was used to estimate survival outcomes, and the groups were compared using the log-rank test. Survival time was calculated from the date of diagnosis or transformation (progression to sPCL) to last known visit, or death. Cox regression model was used to identify prognostic factors for overall survival (OS).

Results: In our institutional registry, we identified 25 patients (pts) with pPCL and 19 pts with sPCL. Among those who progressed, median time of progression to sPCL was 42.8 months (range: 9-119.2). Median age at diagnosis was 56 years (range: 35-80) for pPCL and 67 years (range: 40-83) for sPCL; no difference in terms of gender, race, myeloma type, or cytogenetic risk was noted. While the percentage of circulating PCs was comparable in the two groups (26% versus 38%), the median LDH values were higher in pts with sPCL (median LDH in pPCL: 278 U/L, range: 108-2718; median LDH in sPCL: 530 U/L, range: 145-3232; p = 0.008), to indicate rapid disease kinetics. In terms of immunophenotype of the MM cells, median CD56 clone size was higher in sPCL compared with pPCL (sPCL = 46.3%; pPCL = 24.7%), while median CD38 and CD28 clone sizes were lower (CD38: sPCL = 74%; pPCL = 98%; CD28: sPCL = 9.3%; pPCL = 27%). As initial therapy, 16/25 (64%) pts with pPCL received a bortezomib-lenalidomide-dexamethasone (VRD) or carfilzomib-lenalidomide-dexamethasone (KRD) regimen, 6/25 (24%) received CyBorD, and 3/25 (12%) received VD-PACE. Induction therapy was followed by autologous stem cell transplant in 11/25 pts. 3 of these 11 pts also underwent allogeneic stem cell transplant at relapse.

In contrast, pts with sPCL were already heavily pre-treated at time of transformation (median prior lines: 5, range: 1-12). 8/19 of them did not receive treatment and succumbed to progressive disease. The other 11 pts received a chemotherapy-based regimen (4/11, 36%), a carfilzomib-based regime (5/11, 45%), or an anti-CD38 antibody-based regimen (2/11, 19%). The median OS for all pts was 6.9 months (95% CI: 3.1-21.6), with pPCL having a significantly longer median OS of 26.0 months (95% CI: 14.8-NR) compared to sPCL's 1.6 months (95% CI: 0.5-4.4) (p &lt; 0.001). The 1-year OS estimates for pPCL and sPCL were 67% (95% CI: 51-89) and 5% (95% CI: 1-35), respectively.Variables associated with an inferior OS in both the univariable and multivariable analysis were the presence of sPCL, 1q+, and LDH values at presentation.

Conclusions: The introduction of novel therapies has overall improved the outcomes of pts with PCLs; however, their OS remains inferior compared to pts with MM. In addition, the prognosis of pts with sPCL is particularly poor with a median OS of 1.6 months compared to 26.4 months for pts with pPCL. Except for differences in LDH levels, rates of 1q+, and immunophenotype of MM cells, no other differences were noted between pPCL and sPCL, to suggest that the more aggressive features and resistance to therapies of sPCL is not accounted by standard prognostic scoring. Further studies using whole-exome sequencing, RNA-sequencing, and CITE-sequencing will be helpful to further understand the biological differences between pPCL and sPCL.