SIERRA: Iomab-B–based conditioning improves bone marrow transplant outcomes in R/R AML

The anti-CD45 radioimmunoconjugate Iomab-B has been shown to safely deliver myeloablative doses of targeted radiation to the bone marrow of older patients with relapsed/refractory acute myeloid leukemia (R/R AML), improving the outcomes of subsequent allogeneic haematopoietic stem cell transplantation (HSCT).

In the pivotal phase III SIERRA trial, “Iomab–B-based conditioning with HSCT resulted in rapid engraftment and high initial complete remission (CR) or CR with incomplete platelet recovery (CRp) rates, [while having] a favourable toxicity profile,” reported lead researcher Dr Boglarka Gyurkocza of Memorial Sloan-Kettering Cancer Center, Manhattan, New York, US at EHA 2023.

SIERRA included patients with active R/R AML and were at least 55 years of age. They were randomly assigned to receive either Iomab-B with fludarabine and total body irradiation (2 Gy) or conventional care (control) followed by HSCT. Patients in the control group who achieved CR were afterwards given physician’s choice conditioning and HSCT (noncrossover group), while those who did not achieve CR could crossover to Iomab-B-based conditioning followed by HSCT (crossover group).

Gyurkocza and colleagues assessed the patients for CR/CRp between days 28 and 56 after HSCT or initiation of therapy in the control arm. Those who achieved CR/CRp were evaluated for the primary endpoint of durable CR, defined as having CR for ≥6 months with or without platelet recovery.

Of the evaluable patients, 44 of 59 (74.6 percent) in the Iomab-B arm achieved initial CR/CRp compared with only four of 64 (6.3 percent) in the control arm. Durable CR rates were significantly higher in the Iomab-B group (22 percent vs 0 percent; p<0.0001). [EHA 2023, abstract S248]

Overall survival (OS) was significantly longer in the Iomab-B arm than in the noncrossover group in the control arm (median, 6.4 vs 3.2 months), as well as in the crossover group vs the noncrossover group in the control arm (median, 7.1 vs 3.2 months). Iomab-B halved the risk of death (hazard ratio [HR], 0.51, 95 percent confidence interval [CI], 0.31–0.85; p=0.0078).

Treatment with Iomab-B was also associated with a higher likelihood of event-free survival (EFS) at 6 months (26 percent vs 0.2 percent; HR, 0.22, 95 percent CI, 0.15–0.34; p<0.0001).

As for safety, “Iomab-B-based conditioning followed by HSCT was well tolerated,” with lower rates of sepsis in the Iomab-B arm than in the control arm, Gyurkocza noted.

These findings have important clinical implications, given that prognosis for patients with relapsed or refractory disease remains poor despite recent advances in the treatment of AML, according to the researcher. “The only potentially curative option for these patients is allogeneic HSCT.”

Based on the present data, Gyurkocza is positive that Iomab-B may improve the access to HSCT for the majority of older patients who do not reach complete remission or sufficient disease control to allow for HSCT, as well as for those who poorly tolerate induction and conditioning regimens.

In the SIERRA population, baseline characteristics were balanced between the two treatment arms. Most patients (61 percent) experienced targeted therapy failure prior to enrolment, of whom 66 percent received venetoclax-based therapy. Median time to HSCT was 29 and 66.5 days in the Iomab-B and control arms, respectively. The median infused activity of Iomab-B was 664.4 and 613.3 mCi in the Iomab-B arm and in the crossover group of the control arm, respectively, with median dose to marrow of 16 Gy in both arms. HSCT was performed in all patients who received the therapeutic dose of Iomab-B as opposed to only 14 (18.2 percent) in the control arm.