A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma

Abstract

Summary:The overall survival of patients with advanced multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (SCT) depends mainly on the quality of response. Thus, to improve the response rate, a new intensified high-dose chemoradiotherapy was evaluated in a phase I/II study. After induction chemotherapy, 89 patients (median age 51 years, range 32-60 years) with MM stage II/III received a conditioning regimen with total marrow irradiation (9 Gy), busulfan (12 mg/kg) and cyclophosphamide (120 mg/kg) followed by SCT. Regimen-related toxicity according to WHO criteria and response rates defined by EBMT/IBMTR were analyzed. The main toxicity was mucositis grade III/IV in 76%, and fever grade 4I in 75% of patients. Three patients developed reversible venoocclusive disease. Transplant-related mortality was 2%. Among patients with de novo and pretreated MM, a CR rate of 48 and 41%, respectively, was documented. With a median follow-up of 45 months, the actuarial median durations of event-free survival (EFS) and overall survival (OS) after transplant were 29 and 61 months for the whole group, 36 and 85 months for patients with de novo MM, respectively. Thus, administration of this intensified conditioning regimen was associated with tolerable toxicity, a high response rate and long EFS and OS.

Myeloablative intensified conditioning regimen with in vivo T-cell depletion (ATG) followed by allografting in patients with advanced multiple myeloma. A phase I/II study of the German Study-group Multiple Myeloma (DSMM)

“…22 We used this conditioning regimen with modified total body irradiation with lung and liver shielding (total marrow irradiation) in combination with busulfan and cyclophosphamide because a high percentage of complete responses was observed in a phase II trial followed by autologous transplantation. 27 Achieving CR after autologous or allogeneic transplantation is a major obstacle for longterm disease-free survival. 5,22 In our study, 53% of the patients achieved a CR after allogeneic transplantation, which could be enhanced by donor lymphocyte infusion to 67%.…”

Consensus statement from European experts on the diagnosis, management, and treatment of multiple myeloma: from standard therapy to novel approaches

“…In this respect it is noteworthy that to date, del(17p13) remains a negative prognostic factor, whereas the adverse impact of t(4;14) might be overcome with allo-SCT [55]. Since it is safe and effective, ASCT as opposed to allo-SCT has become the standard of care in MM, with only 6% of transplant-eligible patients undergoing an allo-SCT while 94% receive an ASCT, thereby making MM the most common indication for ASCT worldwide [56]. Randomized trials have shown that ASCT is superior to conventional chemotherapy, resulting in an improved CR rate (22-44% vs. 5-8%) and a 12-30-month prolongation of event-free survival (EFS) and OS [12-15 ,54] (Table III).…”

High‐dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment‐related mortality in patients with multiple myeloma: results of a randomised study

“…This observation may be biased by the relatively small number of patients because of the early discontinuation of the study. However, other studies that focused on dose intensification and used less intense regimens for single HDT also found no clear benefit with respect to outcome (Meloni et al, 2000;Einsele et al, 2003;Ria et al, 2004). Therefore, it is noteworthy that, in our study, dose-escalation up to a dose-limiting toxicity did not prolong the duration of remission of surviving patients in the intensified treatment arm.…”