High-dose BCNU/Melphalan conditioning regimen before autologous stem cell transplantation in newly diagnosed multiple myeloma

Abstract

Single-agent high-dose melphalan (HDM, 200 mg/m) has been the most commonly used conditioning regimen prior to autologous stem cell transplant, since its introduction in 1992. We used a more aggressive alkylator-based conditioning regimen in an attempt to overcome early relapse and combat drug resistance. We present a retrospective comparison and long-term follow-up of newly diagnosed patients with multiple myeloma (MM) treated with induction followed by either high-dose carmustine (BCNU) and HDM, or HDM alone, both followed by autologous stem cell transplant (ASCT). Between 1997 and 2002, 104 patients were treated with BCNU/HDM; from 2001 to 2008, 103 patients were treated with HDM alone. Median follow-up of survivors was 78 and 68 months for the BCNU/HDM and HDM groups, respectively. The median PFS was significantly increased with the BCNU/HDM regimen (40.4 vs 20.5 months, P<0.001). Median overall survival was increased with the BCNU/HDM regimen when compared with HDM alone (88.4 vs 67.2 months, P=0.07), but the difference was not statistically significant. Transplant-related mortality was similar in both groups (2.9% with BCNU and HDM vs 3.9% with HDM alone). Our findings suggest that the BCNU/HDM preparative regimen should be investigated further and potentially compared in a prospective randomized manner with HDM alone.

The Role of Salvage Second Autologous Hematopoietic Cell Transplantation in Relapsed Multiple Myeloma

“…Costa et al [32] recently showed in a Phase I-II trial that the combination of carfilzomib on days -3 and -2 with Mel200 on day -2 is also very active in high-risk patients with relapsed MM receiving SAT, with a 1year PFS of 67% and a 1-year OS of 88%. Other regimens have evaluated various combinations of cytotoxic agents [33][34][35][36] (NCT03687125), immunomodulatory agents [37], proteasome inhibitors [38], and total marrow irradiation [39] with varying success [40]. Despite the promise of an intensified approach in the upfront setting, this is still not routinely used in the relapsed or upfront setting.…”

Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Therapies

“…Melphalan is the standard chemotherapeutic agent that is used in the conditioning therapy prior to autologous HSCT in MM. The dose ranges between 140 and 200 mg/m 2 , given intravenously (IV) [79,81,82,93]. It is cleared from plasma and urine in 1 and 6 hours, respectively.…”

“…Recently, other drugs have been used in the conditioning therapy prior to autologous HSCT in MM either alone or in combination with HD melphalan [94][95][96][97]. Compared to HD melphalan, the use of ixazomib, BCNU, bortezomib and IV busulfan either alone or in various combinations with HD melphalan in the conditioning therapies has increased the overall response rates and the median OS without additional toxicity [93][94][95][96][97].…”

Stem cell transplant and the potential role of CAR-T cells in multiple myeloma

“…One exception may be Bendamustine, but this has not been fully explored yet [4]. Several other agents like idarubicin, etoposide, busulfan, carmustine and bortezomib were also studied as a substitute for melphalan, while none of them was shown to be superior [5], some were even more toxic than melphalan alone [6,7], and recent studies comparing melphalan and carmustine did not show any diff erence in terms of TRM [8,9]. Furthermore, there is no universal consensus, when it comes to choice of the treatment modalities.…”