Intensity-modulated total marrow irradiation (IM-TMI) combined with fludarabine and melphalan is a feasible conditioning regimen for patients with hematologic malignancies undergoing second allogeneic stem cell transplantation (allo-SCT), according to research published in Blood Advances.
Researchers conducted a single-center, phase 1, modified 3 + 3 dose-escalation study evaluating the feasibility of combining IM-TMI with fludarabine and melphalan for conditioning in patients with relapsed hematologic disease undergoing second or greater allo-SCT between December 2015 and May 2020.
A total of 21 patients (median age, 56 years; range, 22-72 years) were treated with IM-TMI doses of 6 Gy (n=5), 9 Gy (n=10), or 12 Gy (n=6). The primary dose-limiting toxicity (defined as a grade 3 or higher treatment-related adverse event) was mucositis. The researchers determined the maximum tolerated dose for IM-TMI was 12 Gy. A dose of 9 Gy was used at the treating physician’s discretion for some patients who were older or underweight.
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The team observed a median time to neutrophil engraftment of 10 days (range, 8-20 days) and to platelet engraftment of 18 days (13-40 days). They reported a 1-year cumulative incidence of graft-versus-host disease of 65% (95% confidence interval CI, 38-83), 2-year nonrelapse mortality of 17% (95% CI, 4-39), 2-year cumulative incidence of relapse of 35% (95% CI, 13-58), and 2-year progression-free survival and overall survival of 48% and 50%, respectively.
“In this phase 1 clinical trial, we show that combining 12 Gy of IM-TMI with daily fludarabine 30 mg/m2 at days -7 to -3 and melphalan 140 mg/m2 on day -2 is a feasible and well-tolerated conditioning regimen in patients undergoing second or greater allo-SCT,” the investigators concluded in their report.
Limitations of the study included the small sample size, heterogeneous patient population, varying duration of remission from first allo-SCT (median, 11.8 months; range, 1.8-49.8 months), varying time from last relapse to protocol therapy (6.7 months, range, 2.8-84.4 months), and inability to adequately capture late-onset toxicities of the regimen with the follow-up duration used.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures.
Reference
Tran MC, Hasan Y, Wang A, et al. A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT. Blood Adv. 2023;7(3):285-292. doi:10.1182/bloodadvances.2022007530
