The overall survival of patients with advanced multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (SCT) was found to depend 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. 89 patients (median age of 51, range 32 - 60 years) received an intensified conditioning regimen consisting of total marrow irradiation (9 Gy applied in 2 fractions over 3 days with shielding of the lung and liver), high dose busulfan and cyclophosphamide 120 mg/kg (TMI/Bu/Cy) followed by PBSCT. Prior to chemoradiotherapy an induction and mobilization chemotherapy (4 g/m2 cyclophophamide) were administered. Isotypes were IgG in 48, IgA in 23, Light chain disease in 14, IgD in 3 and a non-secretory MM in 1 patient. Stage IIIA MM was diagnosed in 52, stage IIIB in 18, stage IIA in 16, stage IIB in 3 patients. 56 (62%) patients were pretreated at the time of inclusion in the study (35 with 1, 21 with > 1 line of pretreatment). 27 patients had received conventional therapy for > 1 year prior to high dose chemoradiotherapy. Regimen-related toxicity according to WHO criteria and response rates as defined by the EBMT/IBMTR criteria were analysed. TRM was 1% with 1 patient dying of invasive aspergillosis. Three patients developed reversible hepatic veno-occlusive disease (VOD). The main toxicity observed was mucositis WHO grade III/IV in 76%, and fever WHO grade > I in 75% of patients. Among the patients with de novo and pretreated MM a CR rate of 48% and 41%, respectively, was documented. With a median follow-up of 35 months, the actuarial median duration of progression-free survival (PFS) and overall survival (OS) of the whole patient group after transplant were 31 and 58 months, respectively follow up. The actuarial median PFS and OS of patients with de novo MM were 35 and > 60 months, respectively. Thus, administration of this new intensified conditioning regimen was associated with a tolerable toxicity and a high response rate. Due to these promising data, conditioning therapy with TMI/Bu/Cy is currently compared with tandem high dose melphalan in patients with advanced MM in a phase III study.
Full conference title:
43rd American Society of Hematology (ASH) Annual Meeting
- ASH 43rd (2001)