Primary Plasma Cell Leukemia in the Era of Novel Agent: Report of Multicenter Study from Japanese Society of Myeloma.

[Introduction] Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia with poor outcomes. Because of the rarity of the disease, most clinical data have been derived from case reports and small retrospective studies. And accordingly, there has been a limited information about the possible role of novel agents in the treatment of PCL. [Purpose] The objective of this study was to investigate the current treatment status and outcome of Japanese patients with primary PCL (pPCL) in the era of novel agent and to analyze risk factors affecting survival in order to propose an optimal treatment strategy for pPCL in the future. [Patients and Methods] This study was approved by the local institutional review board. Between January 2001 and December 2012, 38 consecutive pPCL patients were treated at the participating hospitals of the Japanese Society of Myeloma among 3318 patients with symptomatic multiple myeloma (MM). Diagnosis was made according to the criteria of International Myeloma Working Group. We investigated clinical characteristics at diagnosis, including age, gender, PS (ECOG), serum biochemistry and hematological parameters, Ig subtypes, the proportion of plasma cells in the bone marrow (BM), cytogenetics including FISH, and clinical stages [Durie & Salmon (DS) staging and International Staging System (ISS)]. The data about treatment regimen, including the first-line and salvage therapy, response rates with first-line therapy and overall survival (OS) were also analyzed. [Results] The incidence of pPCL was 1.1% among patients with symptomatic MM. The median age and male/female ratio were 64 years (range 35-89) and 1.24 (21/17), respectively. The median OS of all pPCL patients was 2.85 years, which was much longer compared with that in the previous reports from USA and Europe. Proportion of patients treated with novel agents during the entire study period was 61% (23/38). OS of the patients treated with novel agents during the period was significantly extended than that of patients treated without novel agents by generalized Wilcoxon test (2.85 years vs 1.16 years, p=0.049); however, there was no significant difference by log-rank test (p=0.28). This finding would implicate that treatment with novel agents could have prevented early death in patients with pPCL. There was no significant difference in OS between patients who received autologous stem cell transplantation (ASCT) and who did not (2.85 years vs 2.34 years). Only age was statistically significant prognostic factor for inferior OS (HR, 4.57). Patients older than 65 years tended to have received treatment without novel agents (47% vs 74%), so the lack of novel therapy might have contributed to the inferior survival of the elderly patients. Five patients received maintenance therapy with novel agents, and OS of these patients tend to be longer than that of the other patients (4.45 years vs 2.85 years). [Conclusion] The incidence of pPCL in Japan was similar to that in USA and Europe; however the OS of Japanese patients was significantly better than that reported from USA and Europe. This might result from the maintenance therapy with novel agents used in Japanese patients. Unlike MM, OS with pPCL has not been improved significantly in the last decade, especially in the elderly patient population, it would be important to establish the treatment strategy, particularly after induction treatment, such as intensification/maintenance therapy.