PB2161 TREATMENT OF PRIMARY PLASMA CELL LEUKEMIA WITH HIGH DOSES OF CYCLOPHOPHAMIDE, BORTEZOMIB AND DEXAMETHASONE FOLLOWED BY DOUBLE AUTOLOGOUS HSCT
Authors: Pagano L. , Maraglino A. E. M. , Criscuolo M. , Fianchi L. , Rossi E. , Za T. , Chiusolo P. , Bonanni M. , Dragonetti G. , Bacigalupo A. , Sica S. , De Stefano V. 
Published: June 2019

Background:Primary plasma cell leukemia (pPCL) accounts for 1–3% of all plasmacellular dyscrasias. The course of this disease is highly aggressive, with unsatisfactory response to therapy, poor prognosis, and a median survival of about 7 months. Conventional treatment adapted from those used for myeloma are ineffective and optimal therapy remains to be defined.Aims:We analyzed the efficacy of a treatment including high doses of cyclophophamide, bortezomib and dexamethasone followed by double autologous HSCT in a monocentric study.MethodsBetween January 1, 2012 and December 31, 2018, 12 adult patients (pts) with a diagnosis of pPCL were observed in our institution. Three pts were excluded, 2 for bad performance status and 1 for early death. The remaining 9 pts received the same front line approach: CTX 1500 mg/mq d 1,8–Bortezomib 1,3 mg/mq d 1,4,8,11 ‐ Dexamethasone 40 mg d 1,2,4,5,8,9,11,12 for 3 courses. The pts who obtained at least a PR after induction therapy underwent stem cell collection with high doses of CTX (4000 mg/mq) and then received double auto‐HSCT. After auto‐HSCT pts received maintenance with continuous lenalidomide 25 mg every day for 21 days followed by one week of rest.Results:All the 9 pts fulfilled diagnostic criteria with an absolute count of peripheral blood monoclonal plasma cells >2 × 109/l. The median plasma cells count was 5646 × 106/l (range 2400‐20000). Regarding clinical and laboratory characteristic, 8 (89%) pts presented the CRAB criteria at the onset: 8 pts had anemia (median Hb 9,6 gr/dl; range 4,7‐13,4); 6 pts had hypercalcemia (median 12,4 mg/dL, range 9,7‐17,3); 6 had acute kidney failure with a median creatinine levels of 3,4 mg/dL (range 0,92‐14,9); 7 pts had bone osteolysis. 5 pts showed a normal karyotype, 1 pts had hypodiploidy, and 3 pts had a complex karyotype. Monoclonal IgG was present in 3 pts, 2 had IgA and the remaining 4 pts had a micro‐molecular component.All received the same induction therapy for 3 courses. At the end of the treatment 6 (67%) patients showed a CR, 2 pts showed a PR and 1 was unresponsive. Five patients received the double auto‐HSCT, while the other 1 is ongoing.Regarding side effects during the induction phase, only 2 pts (22%) showed complications such as infection and neutropenia during induction therapy, regressed through an appropriate treatment; all pts presented a complete resolution of acute kidney failure and hypercalcemia after induction therapy.The median overall survival (OS) for whole population was not reached; at 5 years follow‐up 55% of patients are still alive. Comparing OS of patients who achieved CR with patient in PR after first line treatment a trend of significance could be noted (OS not reached vs 10 months respectively, p‐value = 0.055).Median progression free survival (PFS) for only patients achieving CR after induction therapy was 50 months.Summary/Conclusion:This study shows that a in induction treatment based on high doses of CTX combined with bortezomib followed by 2 procedures of auto‐HSCT could improve the prognosis and survival of these poor prognosis pts when compared to other treatments. No patient had relevant side effects, death in induction or delay in the following treatments. The double autologous transplantation seems effective to reduce the incidence of relapse in this subset of pts.