Primary Plasma Cell Leukemia Has a Poor Prognosis Even in the Era of Novel Agents - a Multicenter Case Series
Authors: Ganzel Chezi , Rouvio Ory , Magen Hila , Jarchowsky Osnat , Avivi Irit , Herzog Katrin , Yossi Cohen , Tadmor Tamar , Horowitz Netanel A , Leiba Merav , Nagler Arnon , Cohen Yael , Bulvik Shlomo , Ben Yehuda Dina , Rowe Jacob M. , Gatt Moshe E. 
Published: October 2019

Abstract
Introduction: Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma (MM), characterized by the presence of 20% and/or 2X109/L plasma cells (PCs) in the peripheral blood (PB) of the patient. Data regarding this entity are scarce and based on case reports and few retrospective case series. Most of the reports are dated prior to the incorporation of novel agents into MM treatment. The aim of this multicenter retrospective study was to evaluate the response and survival of PPCL patients in the era of the novel agents.
Methods: We searched for the diagnosis of PPCL, during the years 2002-2016, in the medical summaries of 16 medical centers in Israel which routinely treat patients with MM. Patients with the presence of plasma cells in the blood during the course of MM (secondary plasma cell leukemia) were excluded.
Results: 40 PPCL patients were identified in 11 of the 16 medical centers. It is probable that several patients were recorded as MM and thus not identified as PPCL. The characteristics of the patients and their disease are available for 35 patients and are summarized in table 1. One third of the patients presented with light chain disease and over two thirds had hypercalcemia at diagnosis. The median age was 60 and 3 patients were aged less than 35 years at diagnosis. The median number of treatments was 2. 83% of the patients received at least one IMiD or proteosome inhibitor (PI), 51% received both IMiD and PI. 17% of the patients received more than one line of IMiDs and a similar number of patients received more than one line of PIs (Fig. 1). The type of novel agents that were used are shown in figure 2. 45.7% of the patients underwent hematopoietic stem cell transplant (HSCT), of those, 4 patients (11%) have undergone tandem auto-allo HSCT and 1 (3%) - tandem auto-auto HSCT.
29% of the patients did not responded to induction therapy and 57% achieved PR or better response. 13 out of 35 patients (37%) are still alive and one is lost to follow-up. The median overall survival (OS) was 11 months.7 patients (20%) survived less than 2 months while 13 (37%) survived more than 24 months, including 7 who survived more than 48 months.
Among the 16 patients who underwent HSCT, all the 4 who underwent tandem auto-allo-transplant survived more than 32 months.
Conclusions: Despite the modest size of this patient cohort, several inferences may be made. Patients with PPCL have unique characteristics compared to MM patients; lower median age, more frequent light chain disease and hypercalcemia at presentation. Extreme leukocytosis or leukopenia are rare. Despite intensive use of novel agents, the median OS of this cohort remains poor - 11 months. The best results were seen in patients who received tandem auto-allo HSCT, suggesting that the immunotherapeutic graft-versus-myeloma effect may offer the best hope for long-term survival to patients with PPCL.
Table 1 Patient and disease characteristics Table 1. Patient and disease characteristics Figure 1 Combinations of novel agents Figure 1. Combinations of novel agents Figure 2 Types of novel agents Figure 2. Types of novel agents

Disclosures
Avivi: Tel Aviv Sourasky Medical center: Consultancy, Other: consultancy to :BMS Roche.