All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit Know AML.

The AML Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Introducing

Now you can personalise
your AML Hub experience!

Bookmark content to read later

Select your specific areas of interest

View content recommended for you

Find out more
  TRANSLATE

The AML Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the AML Hub cannot guarantee the accuracy of translated content. The AML Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact
LOADING
You're logged in! Click here any time to manage your account or log out.
LOADING
You're logged in! Click here any time to manage your account or log out.
2024-06-07T10:41:55.000Z

SIERRA trial post hoc analysis: Outcomes of patients with a TP53 mutation vs wild type

Jun 7, 2024
Share:
Learning objective: After reading this article, learners will be able to cite a new clinical development in the treatment of acute myeloid leukemia.

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 

  • Of the 153 patients enrolled in the trial, 37 patients had a TP53 mutation. 

  • 20 patients were treated with CC and 17 with Iomab-B. 

  • 10 patients from the CC arm crossed over to Iomab-B. 

  • 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). 
  • A TP53 mutation was not associated with an increased risk of complications post allo-HSCT. 

  • The safety profile of patients with a TP53 mutation was comparable to that of the overall Iomab-B treatment population. 

  • 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. 

  • 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). 

Key learnings 

  • Treatment with Iomab-B significantly improved rates of CR in patients with relapsed/refractory disease, regardless of TP53 mutation status. 

  • Iomab-B was well tolerated, and the safety profile of patients with a TP53 mutation was comparable to that of the overall trial population. 

  • Results from this trial support the use of Iomab-B in patients with relapsed/refractory TP53-mutated acute myeloid leukemia. 

  1. 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. 

Newsletter

Subscribe to get the best content related to AML delivered to your inbox