Primary Plasma Cell Leukemia in the Era of Novel Agents: A Multicenter Study of the Japanese Society of Myeloma

Abstract

We investigated the treatment and outcome of Japanese patients with primary plasma cell leukemia (pPCL) in the era of novel agents and analyzed the risk factors affecting survival. Among 3,318 patients with symptomatic multiple myeloma (MM), 38 patients were diagnosed with pPCL. The median overall survival (OS) of the pPCL patients was 2.85 years, which was significantly extended compared with that in previous reports. The proportion of patients treated with novel agents was 61%. The OS of the patients treated with novel agents was significantly extended compared with that of patients treated without novel agents according to the generalized Wilcoxon test (2.85 vs. 1.16 years, p = 0.049). This statistical finding suggests that treatment with novel agents could have prevented early death in the patients with pPCL. Age was the only statistically significant prognostic factor associated with an inferior OS (hazard ratio 4.57). Five patients received maintenance therapy with novel agents, and their OS tended to be longer than that of the other patients without maintenance (4.45 vs. 2.85 years). Unlike MM, OS for pPCL has not been improved significantly over the last decade, especially in elderly patients. Therefore, it is important to establish the treatment strategy, particularly after induction treatment.

Real-world data on prognosis and outcome of primary plasma cell leukemia in the era of novel agents: a multicenter national study by the Greek Myeloma Study Group

“…During the last decades, initially autologous stem cell transplantation 9 (ASCT) and subsequently novel therapies 10 including immunomodulatory drugs and proteasome inhibitors (PIs) namely bortezomib, led to a slight improvement of pPCL patients’ survival 5 . The efficacy of bortezomib in pPCL has been demonstrated by our group and others in small retrospective series 5 , 11 – 13 , however, this has been questioned in other studies 14 , 15 . Recently, a prospective phase 2 study has demonstrated that induction therapy with bortezomib based combinations followed by ASCT led to high response rates and prolonged survival in patients with pPCL 16 .…”

“…The introduction of first generation novel agents, i.e., thalidomide, lenalidomide, and bortezomib has improved response rates and OS 20 of MM patients, therefore it was reasonable to explore their role in PCL 4 , 5 . Novel agent-based therapies and more commonly bortezomib-based combinations were evaluated retrospectively in several case reports and case series, that included limited number of patients, as expected, considering the rarity of the disease 5 , 11 – 13 ; according to those studies, objective response ranged from 56-80% and median OS ranged from 12–31 months, depending on the incorporation or not of ASCT in the induction therapy 5 , 11 – 13 . We have previously suggested that, the efficacy of bortezomib could be at least partially related to abnormal CD27 expression whose triggering on pPCL cells has a significant anti-apoptotic effect involving ERK1/2, NF-kB, and JNK signal transduction pathways 21 .…”

“…We have previously suggested that, the efficacy of bortezomib could be at least partially related to abnormal CD27 expression whose triggering on pPCL cells has a significant anti-apoptotic effect involving ERK1/2, NF-kB, and JNK signal transduction pathways 21 . The majority of studies showed survival advantage in patients treated with bortezomib-based combinations compared to those treated with conventional therapy 11 – 13 however, the number of patients with pPCL included in those studies was limited. At variance, in the study performed by the Intergroup Francophone du Myelome (IFM) 14 there was no survival advantage with the use bortezomib-based combinations, however, the exact number of patients treated with bortezomib, conventional treatments or thalidomide-based regimens was not reported 14 .…”

Retrospective analysis of primary plasma cell leukemia in Kansai Myeloma Forum registry

“…Recently, Iriuchishima et al. reported that novel agents significantly prolonged OS compared to other treatments (2.85 versus 1.65 years, p = 0.049) [9] .…”

Novel Agents for the Treatment of Primary Plasma-Cell Leukemia: Lights and Shadows

“…In this issue of Acta Haematologica , Iriuchishima et al [3] report a national retrospective Japanese survey concerning 38 cases of PPCL collected over a 12-year period. In this study, there was no difference in overall response rates (ORR) to ‘conventional' or novel therapies (68 vs. 67%), but significantly higher rates of complete response and very good partial response were detected in patients treated with novel agents (50 vs. 16%; p = 0.029).…”