Plasma Cell Leukemia - a Single Center Experience
Authors: Mota Diana , Roque Adriana , Pinto Ana Luísa , Geraldes Catarina , Carda Jose Pedro , Gomes Marília , Cortesão Emília , Almeida José Carlos , Araújo Luis Francisco , Espadana Ana Isabel , Ribeiro Maria Leticia 
Published: October 2019

Abstract
BACKGROUND: Plasma cell leukemia (PCL) is a rare disorder representing 2-4% of malignant plasma cell diseases and constitutes their most aggressive form. It presents either as primary disease (pPCL) or as secondary leukemic transformation (sPCL) of multiple myeloma (MM). It has a poor prognosis compared to MM, and the results of conventional therapy are disappointing though autologous stem cell transplantation (aSCT) may improve survival.
AIMS: We aim to evaluate clinical characteristics, prognostic factors and treatment outcome of patients (pts) with pPCL and sPCL.
METHODS: We conducted a single center retrospective study of pts diagnosed since January/2006 to June/2018. The diagnosis was based on the presence of ≥20% or ≥2x109/L peripheral blood (PB) plasma cells (PCs) (WHO, 2016). Response to treatment was evaluated according to IMWG consensus criteria (2016). Statistical analysis was performed with a significant level set at p<0.05. All risk factors with p<0.15 in univariate model were further entered into multivariate analysis.
RESULTS: A total of 24 pts were included, 46% male, with a median age at diagnosis of 67y (44-78). At baseline, most of the pts had a poor performance status (PS), with ECOG≥2 (63%). From those, 66.7% (n=16) had pPCL and 33.3% (n=8) sPCL. In elderly pts (>65y), sPCL was less common (21.4 vs 50%; p=NS). In sPCL, median time from MM diagnosis to sPCL diagnosis was 27.3 months.
IgG was the most frequent subtype (42%), followed by light-chain κ (17%) and λ (17%). Median PB-PCs was 4x109/L (0.4-65) with a median relative proportion of 34% (17-85) by PB smear and 26% (10-71) by flow cytometry. At diagnosis, 75% of pts presented anemia, 38% renal impairment, 31% hypercalcemia, 69% bone disease and 33% extramedullary disease.
According to the International Staging System (ISS), 79.0% had ISS III, 10.5% ISS II and 10.5% ISS I. Abnormal lactate dehydrogenase (LDH) level was present in 71% of pts (median 497 U/L). FISH analysis was performed in 11 pts, 50% presenting high-risk cytogenetic abnormalities [del(17p) and/or t(4;14) and/or t(14;16)]. The expression of CD56 in PB and bone marrow PCs was positive in 82% and 86% of pts, respectively.
Median number of therapeutic lines after PCL diagnosis was 1 (1-4), with 58% of pts receiving a novel agent, and all sPCL pts had been treated with a novel agent previously to the PCL diagnosis.
In our cohort, 1st line therapy included novel agents in 42% pts (bortezomib in 7, IMIDs in 1 and both in 2 pts), 38% received a protocol including anthracycline and 29% pts only received palliative treatment. Overall response rate (ORR) to 1st line therapy in PCL was 42%, being significantly higher in pPCL (56 vs 13%; p=0.04). One third of the pts have received aSCT.
Median overall survival (OS) was 4.1 months, with a significant decreased OS in sPCL (0.4 vs 4.5 months; p=0.002); 71% died directly from disease progression and 29% from other causes. Three-month, 1-year and 2-years OS was 54%, 29% and 17%, respectively.
In our cohort, sPCL (HR 3.41; 95% CI 1.29-8.97; p=0.013) and non-response to 1st line therapy (HR 4.82; 95% CI 1.85-12.57; p=0.001) were associated with increased risk of death. Treatment with bortezomib (any time) was related with a reduced risk of mortality (HR 0.21; 95% CI 0.07-0.62; p=0.005) as well as an anthracycline-based regimen (HR 0.34; 95% CI 0.13-0.85; p=0.022) and aSCT (1.5 vs 18.5 months, p=0.045), but not an IMIDs-based protocol (HR 0.66; 95% CI 0.26-1.73; p=0.40).
On the other side, ISS stage, renal impairment, bone disease, high-risk cytogenetic abnormalities and high LDH levels did not present a predictive value for OS.
In a multivariate analysis only a higher age at diagnosis (HR 0.92; 95% CI 0.86-0.99; p=0.020), and aSCT (HR 0.07; 95% CI 0.01-0.55; p=0.012) predicted higher OS.
CONCLUSIONS: PCL has a poor prognosis and low ORR to conventional treatment. Inversely to MM, no major prognostic improvements have been observed. Although limited by sample size, our study shows that response to 1st line therapy, bortezomib-based and anthracyclines-based regimens as well as consolidation with aSCT improve outcome by lengthening OS, which was not observed with IMIDs-based treatments. A higher age, probably due to a less incidence of sPCL, was also associated with a decreased risk of death.

Disclosures
No relevant conflicts of interest to declare.