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SIERRA trial post hoc analysis: Outcomes of patients with a TP53 mutation vs wild type
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Relapsed/refractory TP53-mutated acute myeloid leukemia is associated with poor prognosis and, due to high relapse rates, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rarely offered.1 131I-apamistamab (Iomab-B) is an anti-CD45 radioimmunoconjugate that delivers targeted radiation to hematopoietic cells, therefore enabling allo-HSCT in patients with relapsed/refractory disease.1 The phase III randomized SIERRA trial (NCT02665065) investigating Iomab-B and allo-HSCT vs conventional care (CC) met its primary endpoint of durable complete remission (CR) lasting at least 6 months.1
During the 50th European Society for Blood and Marrow Transplantation Annual Meeting, Hannah Choe presented results from a post hoc analysis of the SIERRA trial comparing efficacy outcomes and safety of enrolled patients with a TP53 mutation vs wild type. We summarize the results below.
Study design
The overall study design has been previously reported on here.
Key findings1
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Of the 153 patients enrolled in the trial, 37 patients had a TP53 mutation.
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20 patients were treated with CC and 17 with Iomab-B.
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10 patients from the CC arm crossed over to Iomab-B.
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The rates of CR and durable CR were similar in patients treated with Iomab-B, regardless of TP53 mutation status (Figure 1).
Figure 1. Rates of A CR and B durable CR in patients treated with Iomab-B or CC who were TP53 mutation positive or TP53 wild type*
CC, conventional care; CR, complete remission; Iomab-B, 131I-apamistamab.
*Adapted from Choe.1
†27 patients treated with Iomab-B, and 10 patients treated with conventional care.
‡93 patients treated with Iomab-B, and 23 patients treated with conventional care.
§Iomab-B group also included patients who crossed over from the CC group.
- The median overall survival was higher in TP53 mutation-positive patients treated with Iomab-B vs CC (5.49 months vs 1.66 months; hazard ratio = 0.23, p = 0.0002).
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A TP53 mutation was not associated with an increased risk of complications post allo-HSCT.
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The safety profile of patients with a TP53 mutation was comparable to that of the overall Iomab-B treatment population.
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Sepsis was experienced by 17.4% of patients with a TP53 mutation treated with Iomab-B vs 9.6% of patients who were TP53 wild type and treated with Iomab-B.
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The cumulative incidence of acute graft-versus-host disease was comparable between patients treated with Iomab-B who were TP53 mutation positive or TP53 wild type (8.7% vs 8.6%, respectively).
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Key learnings |
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- Choe H. 131I-apamistamab-led allogeneic hematopoietic cell transplant demonstrates survival benefit and overcomes high-risk TP53 mutations in patients with r/r AML. Oral abstract #OS17-02. 50th European Society for Blood and Marrow Transplantation Annual Meeting; April 17, 2024; Glasgow, UK.
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