Bortezomib-doxorubicin-cyclophosphamide-dexamethasone induction followed by stem cell transplantation for primary plasma cell leukemia: a prospective phase II study of the IFM

Purpose Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis: with conventional chemotherapy, patients typically die within one year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in pPCL patients in order to assess the efficacy of an alternate regimen combining standard chemotherapy, a proteasome inhibitor, high dose melphalan and autologous transplantation (HDM/ASCT), followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. Patients and methods Patients ≤ 70-years old with newly diagnosed pPCL received 4 alternate cycles of bortezomib-dexamethasone plus doxorubicin (PAD) or cyclophosphamide (VCD). Peripheral blood stem cells were collected for responding patients with less than 1% of circulating plasma cells prior to HDM/ASCT. As consolidation, young patients received a reduced intensity conditioning (RIC) allograft, whereas the remaining patients underwent a second HDM/ASCT followed by one year of bortezomib-lenalidomide-dexamethasone. The primary end point was progression free survival (PFS). Results Forty patients with a median age of 57 years (range 27-71) were enrolled. The median follow-up was 28.7 months. In the intent-to-treat analysis, the median PFS and overall survival (OS) were 15.1 (95%CI [8.4; -]) and 36.3 months (95%CI [25.6; -]) respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT: 16 of them subsequently received a RIC-allograft, 7 a second ASCT followed by maintenance. Conclusion In this prospective trial in patients with pPCL, we showed that PAD/VCD induction followed by transplantation induced high response rates and appears to significantly improve progression free survival