Abstract
Abstract 4960
High-dose melphalan (HDM) with autologous stem cell transplantation (ASCT) is the standard of care for myeloma (MM) patients aged < 70 years. Achievement of complete/very good partial response (CR/VGPR) is prognostic for improvement overall survival (OS) and use of more effective induction regimens prior to HDT-ASCT may result in improvement post-transplant responses. We performed a retrospective analysis of newly MM pts treated with bortezomib-doxorubicin-dexamethasone (PAD) prior HDM-ASCT.
From October 2005 and July 2008, 20 previously untreated MM pts were enrolled: median age was 56 years (range 44-68), 50% male. Of them, 3 had primary plasma cell leukemia (pPCL), 5 were on dialysis for MM-related renal impairment. Cytogenetic was available for 9: 2 (1 pPCL and 1 MM) had t(4;14). PAD included Bortezomib (1.3 mg/m2 on D1, 4, 8, 11), doxorubicin (9mg/m2 D1-D4), dexametasone (40mg D1-D4): 4 cycles (13 pts), 3 (6 pts), and 2 (1). Response rates after PAD were CR 10%, VGPR 50%, PR 20%, SD 10%. 1 pt died of pulmonary hypertension related to MM after 2 cycles of PAD. Neurologic toxicity ' grade 2 was observed in 3 pts and DVT in 1.
Following induction, 17 pts underwent PBSC harvesting: cyclopsphamide + G-CSF (8), G-CSF only (10). Median yields were 7.9 106 CD34/kg (6-10.5). 17 pts underwent HDM: 200 mg/m2 (12 pts) and 140 mg/m2 (5 pts with renal insufficiency, including 3 on dialysis), followed with ASCT. 1 pt benefited a double HDM/ASCT and 1 (pPCL) a mini-allotransplant 3 monts after. There was no treatment related mortality.
Response rates 3 months post ASCT (17 pts) were: CR 18%, VGPR 70%, PR 6%, SD 6%. 1 SD post PAD obtained VGPR after Thal-Dex had double HDM/ASCT with CR.
With a median follow-up of 23 months (7-34), median OS has not been reached and 1-year survival was 95%. At the reference date of July 2009 85% are alive, 5 pts relapsed: median 12 months (6-14), EFS was 31 months and 2 pts with t(4;14) are alive in CR/VGPR at 23 and 31 months
Concerning the 3 pPCL pts: 1 remained alive in CR 12 months post allo-transplant (follow-up 23 months), 1 was in CR post PAD and relapsed 11 months post HDM/ASCT (survival = 20 months) and 1 is alive at 12 months from diagnosis with a refractory disease. Dialysis could be interrupted for 3 pts in CR/VGPR: 1 after PAD, 2 after ASCT..
In conclusion, according to previously published results (Popat R, British Journal of Haematology 2008), PAD regimen in preparation of HDM/ASCT is safe and highly active in MM patients. Moreover, prolonged remissions and survivals could be obtained in pPCL patients and reversal of severe renal insufficiency observed.
Disclosures
No relevant conflicts of interest to declare.
Consolidation therapy with autologous stem cell transplantation in plasma cell leukemia after VAD, high-dose cyclophosphamide and EDAP courses: a report of three cases and a review of the literature
