Dose escalation by adding Y-anti-CD25 RIT at 0.3 mCi/kg to 12 Gy TMLI was safe, including in older patients, with no dose-limiting toxicities, mean critical organ doses lower than conventional myeloablative TBI, and encouraging response rates. The toxicity profile and dose estimates at 0.3 mCi/kg predict that the planned higher dose levels will also be feasible with acceptable toxicities. RIT and TMLI are complementary and when combined address the limitations of each modality. Combining these targeted therapies may be a superior strategy to intensify dose to leukemia compared to dose escalation of either modality alone.

This TMLI 20 Gy only conditioning regimen, together with PTCy and tacrolimus, is associated with low toxicity and NRM. All patients achieved engraftment. Participants with ≥ 1-year follow-up have discontinued immunosuppressive therapy. The results suggest an improved GRFS rate compared to traditional myeloablative regimens reported. A larger phase II trial is planned.

To our knowledge, this is the largest analysis to date of patients treated with TMLI. Relapse incidence was as frequent in regions receiving ≥12 Gy as those receiving < 12 Gy, suggesting TMLI is not associated with an increased EM relapse risk. These patients did not have significantly different OS compared to historical controls. RT is an effective modality to treat EM relapse in patients with acute leukemia who were previously treated with TMLI.