Dataset Information

A Phase 1 Study of Intravenous Busulfan as a Conditioning Regimen for Multiple Myeloma.

ABSTRACT: The efficacy of melphalan (MEL) 140 mg/m2 pre-transplant conditioning versus MEL 200 mg/m2 for the elderly is still debated. We hypothesized that single-agent intravenous busulfan (BU) would show significant anti-myeloma efficacy and be better tolerated by elderly patients. A prospective 3+3 dose escalation study enrolled symptomatic multiple myeloma (MM) patients 65 years or older with SWOG performance 0-2 for treatment with intravenous BU pre-transplant at different administration levels. The primary objective was to determine the maximum tolerated dose (MTD) of BU that could be safely given over the least number of days. All patients, except one, received maintenance treatment post-transplant, mostly for 2 years. We enrolled 13 patients, mean age of 73 years (range 68-80). Pharmacokinetic analysis showed no greater than 2% accumulation in the 13 patients, confirming a lack of accumulation in the multi-dose regimen. No deaths occurred in the peri-transplant period. Grade 3/4 adverse effects were hematological, no dose-limiting toxicity was observed and MTD was not reached. Three patients developed grade 3 mucositis but none developed veno-occlusive disease. Ten (77%) patients achieved a complete remission (CR) post-transplant with a remarkably long average time to best response of 6.7 months (range: 6-14 m), and two attained a partial response. Median overall survival was 84 months (95% CI, 21-104) and the median progression-free survival was 60 months (95% CI, 9-93). Our results suggest that IV BU could be an alternative conditioning regimen to MEL 140 in elderly patients with MM, and supports future randomized trials.

SUBMITTER: Radhakrishnan SV

PROVIDER: S-EPMC6923548 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Phase 1 Study of Intravenous Busulfan as a Conditioning Regimen for Multiple Myeloma.

Radhakrishnan Sabarinath V SV Boyer Michael M Sherwin Catherine M CM Zangari Maurizio M Tricot Guido G

Cell transplantation 20191016 12

The efficacy of melphalan (MEL) 140 mg/m<sup>2</sup> pre-transplant conditioning versus MEL 200 mg/m<sup>2</sup> for the elderly is still debated. We hypothesized that single-agent intravenous busulfan (BU) would show significant anti-myeloma efficacy and be better tolerated by elderly patients. A prospective 3+3 dose escalation study enrolled symptomatic multiple myeloma (MM) patients 65 years or older with SWOG performance 0-2 for treatment with intravenous BU pre-transplant at different admin ...[more]

PMID: 31619057

Similar Datasets

Project description:BackgroundRetrospective studies suggest that conditioning therapy with busulfan plus melphalan could result in longer progression-free survival compared with melphalan alone in patients with multiple myeloma undergoing autologous haemopoietic cell transplantation (auto-HCT). We aimed to test this hypothesis in a randomised trial.MethodsThe primary objective of the study was to compare progression-free survival with conditioning of busulfan plus melphalan with melphalan alone in patients with multiple myeloma. Patients with newly diagnosed multiple myeloma who were eligible for cell transplantation, aged 70 years or younger, with at least stable disease, were randomly assigned (1:1) to treatment. Patients received either busulfan plus melphalan, with a test dose of busulfan 32 mg/m2 followed by pharmacokinetically adjusted doses on days -7, -6, -5, and -4 to achieve a target daily area under the curve (AUC) of 5000 mmol-minute and melphalan 70 mg/m2 per day on days -2 and -1 (total melphalan dose 140 mg/m2), or a melphalan dose of 200 mg/m2 on day -2. Randomisation was performed via a Clinical Trial Conduct Website at the University of Texas MD Anderson Cancer Center. The accrual is complete and final results are presented here. The study is registered with ClinicalTrials.gov, number NCT01413178.FindingsBetween Oct 12, 2011, and March 22, 2017, 205 patients were assessed for eligibility and randomly assigned to treatment. The primary analysis of progression-free survival was measured in 202 patients who received treatment: 104 patients in the busulfan plus melphalan group and 98 patients in the melphalan alone group. 90 days after auto-HCT, 102 (98%) of 104 patients given busulfan plus melphalan and 95 (97%) of 98 patients given melphalan alone achieved partial response or better. The median follow-up in the busulfan plus melphalan group was 22·6 months (IQR 15·2-47·1) and 20·2 months (IQR 8·8-46·6) in the melphalan alone group. Median progression-free survival was 64·7 months (32·9-64·7) with busulfan plus melphalan versus 43·5 months (19·9-not estimated) with melphalan alone (hazard ratio 0·53 [95% CI 0·30-0·91]; p=0·022). There were no treatment-related deaths by day 100 in either group. Grade 2-3 mucositis was observed in 77 (74%) of 104 patients in the busulfan plus melphalan group versus 14 (14%) of 98 patients in the melphalan alone group.InterpretationThese findings, if confirmed in other ongoing studies, suggest that busulfan plus melphalan could replace melphalan alone as the conditioning regimen for auto-HCT in patients with newly diagnosed myeloma.FundingThis study was funded in part by the National Institutes of Health (NIH) through MD Anderson's Cancer Center Support Grant (CA016672).

Dataset Information

A Phase 1 Study of Intravenous Busulfan as a Conditioning Regimen for Multiple Myeloma.

Publications

A Phase 1 Study of Intravenous Busulfan as a Conditioning Regimen for Multiple Myeloma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets