Decreasing Post-Transplant Relapse With Conditioning Regimens

Conditioning regimens of varying levels of efficacy and toxicity can help decrease the risk for relapse after hematopoietic cell transplantation (HCT) according to a review presented at the 2017 BMT Tandem Meeting (the combined annual meetings of the Center for International Blood and Marrow Transplant Research and the American Society for Blood and Marrow Transplantation). Transplant physicians, including Sergio A. Giralt, MD, from Memorial Sloan Kettering Cancer Center in New York, reviewed the spectrum of newer regimens, including those targeting the CD45 antigen, which may eliminate cells that could be resistant to current strategies.

A regimen containing iomab-B, an anti-CD45 antibody drug conjugate, was evaluated in 58 patients with advanced acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) prior to undergoing HCT. In the first stage, patients received iomab-B plus total body irradiation in escalating 2-Gy doses until a dose-limiting toxicity (DLT) was reached. In the second stage, patients were started at the next-lowest dose and radiation doses were again escalated in 2-Gy increments until a DLT was reached.

The maximum tolerated dose was estimated at 24 Gy. Ten days after treatment, patients received reduced-intensity fludarabine at 30 mg/m2 per day with radiation therapy. At a 1-year follow-up, study authors reported that the rate of non-relapse mortality was 22 percent, the relapse rate was 40 percent, and overall survival was 41 percent.

Another ongoing study is comparing an iomab-B conditioning regimen using high-dose, targeted radiation with conventional care prior to HCT in patients with relapsed/refractory AML. Though this is a reduced-intensity conditioning regimen, it will deliver targeted radiation to the tumor bed in hopes of increasing efficacy while limiting toxicities.

Dr. Giralt reviewed options for optimizing the delivery of currently available options, including a trial investigating methods for adjusting doses of intravenous busulfan in patients with AML or MDS. Targeting an average daily area under the curve of 6,000 µmol/min appeared to extend event-free survival in these patients.

Source: Giralt SA. Clinical outcomes of new and emerging targeted conditioning regimens. Presented at the 2017 BMT Tandem Meetings; February 23-26, 2017; Orlando, Florida.

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