Busulfan, melphalan, and bortezomib compared to melphalan as a high dose regimen for autologous hematopoietic stem cell transplantation in multiple myeloma: long term follow up of a novel high dose regimen

Abstract

Melphalan at a dose of 200 mg/m 2 (MEL200) remains the standard high dose therapy before autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Intensifying the high dose regimen has shown promising results. We report here 7-year follow up of our novel high dose regimen of busulfan and melphalan followed by bortezomib (BuMelVel). Forty-three MM patients received BuMelVel high dose therapy with pharmacokinetic adjusted busulfan. Outcomes were compared to a matched control cohort from the CIBMTR database (n ¼ 162) receiving MEL200. The primary endpoint was progression free survival. Five year PFS was 47% v 30% (95% CI; 32-62) in favor or the BuMelVel group (95% CI; 23-37) (p ¼ 0.05). In multivariate analysis for PFS, BuMelVel (HR 0.65; 95% CI 0.44-0.97)(p ¼ 0.036) was predictive. Similar to recent reports of double alkylator therapy, although depth of response was similar between the BuMelVel group and MEL200, the BUMELVEL group experienced an improved PFS.

Busulfan, melphalan and carfilzomib high‐dose chemotherapy and autologous haematopoietic stem cell transplantation in multiple myeloma

“…Our own group has previously investigated bortezomib in combination with the dual alkylator backbone of BuMel (BuMelVel). When compared to a cohort of matched CIBMTR controls, we noted an improved PFS with a 5‐year PFS of 47%, even without IMiD maintenance, with 7‐year follow‐up continuing to show this advantage 11,18 . These results suggest that BuMelVel alone may reach the same median PFS as BuMel+maintenance IMiD in the MD Anderson study 19 …”

“…However, the addition of oral busulfan has been shown to worsen short‐term toxicity in particularly mucositis, veno‐occlusive disease (VOD) and febrile neutropenia (FN) which has tempered enthusiasm and uptake of this intensified regimen 3,7–10 . Palifermin, a keratinocyte colony stimulating factor, has demonstrated efficacy in mitigating mucositis in several studies, although not in all 11–13 . VOD has been largely eliminated with pharmacokinetic (PK)‐directed IV Busulfan in these regimens 14 .…”