Iomab-B Led Allogeneic Hematopoietic Cell Transplantation vs Standard of Care for Older Patients With R/R AML

Long-term Results of the Phase 3 SIERRA Trial

In a long-term follow-up of the phase 3 SIERRA trial, conditioning and induction with 131I-apamistamab (Iomab-B), an anti-CD45 radioimmunoconjugate, was well-tolerated and allowed for access to allogeneic hematopoietic cell transplantation (HCT) with curative potential for older patients with relapsed/refractory (R/R) acute myeloid leukemia (AML).

These results were presented at the 2024 European Hematology Association (EHA) Congress in Madrid, Spain by James M Foran, MD, Mayo Clinic, Jacksonville, Florida. 

“Most older patients with relapsed or refractory acute myeloid leukemia cannot tolerate intensive treatment and are not eligible for curative allogeneic hematopoietic cell transplant,” explained Foran and coauthors, “With better disease control and safer access to HCT, Iomab-B led induction/conditioning can improve outcomes in pts with active R/R AML.”

The SIERRA trial was a multi-center, randomized, controlled phase 3 study comparing Iomab-B-based conditioning vs physician’s choice of conventional care (CC) for patients 55 years of age or older with active R/R AML. In the trial, these patients were randomized to CC or Iomab-B with fludarabine and total body irradiation followed by HCT. The primary end point was durable CR (dCR), defined as CR/CRp ≥6 months. CR/CRp assessment was 28 to 56 days post HCT on the Iomab-B arm or 28 to 42 days post start of CC. Patients not achieving CR/CRp could crossover (CO) to Iomab-B. The primary analysis of efficacy with positive outcomes were documented at the data cutoff of June 2022, with a long-term results cutoff of January 2024.

In the trial, baseline patient characteristics were balanced between both arms. The 66 patients who received the therapeutic dose of Iomab-B underwent HCT vs 14 (18.2%) patients on the CC arm. Of the evaluable patients (Iomab: 59; CC: 64), 44 (74.6%) patients on the Iomab-B arm achieved initial CR/CRp compared to 4 (6.3%) on the CC arm. The durable CR rates were 22% vs 0% (95% confidence interval [CI]; 12.29 to 34.73.) The median duration of follow-up was 36.6 months (95% CI, 24.8 to 49.4) at the primary analysis cutoff, and 43.6 months (95% CI, 35.1 to 60.9) for the additional analysis.

Using the 2-stage estimation model, the median overall survival (OS) was found to be 6.3 months (95% CI 5.1 to 7.9) months in the Iomab-B arm and 4.0 months (95% CI, 3.0 to 5.1) in the CC arm (HR 0.69 [95% CI, 0.49 to 0.97]; P=0.0314) at the January 2024 data cutoff. Of the 13 patients who achieved a dCR with Iomab-B, 92.3% were alive at 12 months, 69.2% were alive at 24 months, and the median OS has not been reached (NR) (95% CI, 13.5 to NR). In this trial, a grouped survival analysis performed by investigators showed that event-free survival (EFS) was longer in the Iomab-B arm than the CC arm in the ITT population (HR 0.23; 95% CI, 0.15 to 0.34.) The EFS rate 180 days after randomization was higher in the Iomab-B (25.8%) than the CC arm (0.3%). The median EFS assessed by actual time was the same at both cut-off dates.

As for adverse events, the Iomab-B-led regimen followed by HCT was well-tolerated with a favorable safety profile. The rates of sepsis and mucositis for patients receiving Iomab-B-led HCT were lower compared to patients undergoing the standard of care HCT. Study authors found that for patients 55 years or older with active R/R AML, an Iomab-B-led regimen with HCT resulted in high initial CR/CRp rates and also led to statistically significant improvement as as to the primary end point of durable CR.

“The improved outcomes in the Iomab-B treated [patients] persisted when analysis was performed with longer follow up,” Foran and study authors concluded. “The Iomab-B-led regimen was well-tolerated and provided access to HCT with curative potential in a vulnerable [patient] population traditionally not considered eligible for HCT.”

Source:

Foran JM, Gyurkocza B, Nath R, et al. Long term efficacy results of the SIERRA trial: a phase 3 study of 131I-apamistamab-led allogeneic hematopoietic cell transplantation versus conventional care in older patients with active, R/R AML. Presented at the European Hematology Association 2024 Congress June 13-June 16, 2024. Madrid, Spain. Abstract P1377