Primary Plasma Cell Leukemia: Results of a Retrospective Italian Multicentric Survey.
Authors: Pagano Livio , Valentini Caterina Giovanna , De Stefano Valerio , Venditti Adriano , Visani Giuseppe , Petrucci Maria Teresa , Candoni Anna , Specchia Giorgina , Visco Carlo , Pogliani Enrico Maria , Ferrara Felicetto , Galieni Piero , Gozzetti Alessandro , Avvisati Giuseppe , Leone Giuseppe , Musto Pellegrino , Pulsoni Alessandro 
Published: October 2019

Abstract
Abstract 2885
Poster Board II-861

Background:
Epidemiological and clinical information on Primary Plasma Cell Leukemia (pPCL) are rarely reported.

Aims:
To evaluate in patients (pts) with pPCL the clinical features, the prognostic factors, and the efficacy of treatments.

Patients and Methods:
A multicenter retrospective cohort study was carried out between January 2000 and December 2008 in 26 Italian hematology divisions. A total of 128 cases of PCL were collected, and 73 of them (57%) were classified as primary (M/F 43/30).

Results:
The median age was 63 years (range 32-86). At diagnosis the median values of peripheral blood plasma cells and bone marrow plasma cell infiltration were 2.7 × 10 9/L (range 0.4-49.9) and 80% (range 37-100), respectively. The median values of hemoglobin, white blood cell count, and platelet counts were 9.1 g/dl (range 4.8-12.9), 13.7 × 10 9/L (range 1.3-56.7), 116 × 10 9/L (range 8-428), respectively. Extramedullary disease was present in ten cases (14%) and included testis, muscular, neuromeningeal, and cutaneous localization. At diagnosis, 64 pts (88%) had at least one CRAB sign, namely 35 pts (48%) had low hemoglobin level, 20 pts (27%) calcium ≥11 mg/dl, 32 pts (44%) creatinine ≥2 mg/dl, and 47 pts (64%) had osteolysis. In 41 pts (56%) cytogenetic study was performed, revealing an unfavourable karyotype in 17 (23%), in 13 of them del(13q-). Seventy-two pts received front-line therapy (1 died early, receiving only support treatments and steroids), that included antracycline-containing regimens in 36 pts (50%), and single alkylating agents in 17 pts (24%, 9 cyclofosfamide and 8 melphalan). In 11 of them Bortezomib (BTZ, n= 7) or Thalidomide (THAL, n= 4) were also employed. Finally, 19 pts (26%) received BTZ (4) or THAL (5) or both (10) as unique treatment. Twenty-one pts (29%) underwent autologous stem cell transplantation (SCT) as part of front-line therapy, followed by allogeneic-SCT in four cases; two additional pts underwent only allogeneic-SCT. A complete or partial remission after front-line therapy was achieved in 20 pts (27%) and 19 pts (26%) respectively (overall response rate 53%). The median overall survival (OS) was 13.1 months (range 0.5-75.8); 30.6 months (range 4.7-75.8) in responder pts and 4.2 months in non-responder ones (range 0.5-75.6, univariable hazard ratio, HR, 0.28, 95% CI 0.11-0.39). In the responder pts the median progression free survival (PFS) was 17.2 months (range 1.4-72.1). Of note, in SCT pts the median OS and PFS were 38.1 months (range 4.8-75.8) and 25.8 months (range 1.4-72.1) respectively, with a significant advantage with respect to non-transplanted pts in OS (median 9.1 months, range 0.5-75.6, HR 0.28, 95% CI 0.16-0.52) and in PFS (median 7.3 months, range 1.7-17.7, HR 0.29, 95% CI 0.04-0.44). The low number of allo-SCTs did not allow a reliable separate statistical analysis. A multivariable Cox proportional hazard regression analysis showed that OS was influenced by lack of initial response (HR 2.62, 95% CI 1.04-6.57), albumin <3 g/dl (HR 3.33, 95% CI 1.64-6.76), and SCT (HR 0.34, 95% CI 0.12-0.98). Pts with hypercalcemia at diagnosis had a shorter PFS (HR 4.0, 95% CI 1.04-15.24); the PFS was favourably influenced by SCT (HR 0.05, 95% CI 0.009-0.28). Overall, the use of BTZ and/or THAL did not influence the OS and PFS.

Conclusions:
pPCL is a highly aggressive lymphoprolipherative malignancy, characterized by a poor prognosis and a low response rate to conventional therapy. The use of high-dose chemotherapy followed by autologous or allogeneic-SCT is a very effective therapy leading to 66% increase in the OS and to 95% increase in PFS in respect to non-transplanted pts. Apparently, the use of novel drugs such as BTZ and THAL did not produce a further amelioration in the patient outcome. However, those latter findings should be taken with caution, given the relatively low number of treated pts.

Disclosures:
No relevant conflicts of interest to declare.