131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant for Patients with TP53 Mutated R/R AML Results in Significantly Improved Outcomes
Year: 2024
Type: article
Abstract: Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy for relapsed or refractory (R/R) AML patients (pts). Due to high post-HCT relapse rates and high mortality, a minority of pts with TP53 mutations are offered HCT. Iomab-B (131I-apamistamab), an anti-CD45 radioimmunoconjugate, delivers high dose targeted radiation to hematopoietic cells, allowing for myeloablation and eradication of leukemic cells while also limiting off target toxicity. With better disease control and safer access to HCT, Iomab-B led induction/conditioning can potentially improve outcomes even in pts with TP53 mutation. We report characteristics and outcomes of pts with TP53 mutations enrolled in the SIERRA trial. SIERRA (NCT02665065) was a multi-center, randomized, controlled phase 3 study comparing the efficacy of Iomab-B based conditioning vs physician's choice of Conventional Care (CC) in pts ≥55 years of age with active, r/r AML. Pts were randomized (1:1, N=153) to CC or Iomab-B with fludarabine and total body irradiation (2 Gy) followed by HCT (CC, n=77; Iomab-B, n=76). Primary endpoint was durable CR (dCR), defined as CR/CRp ≥6 mos. CR/CRp assessment was 28-56 days post HCT on the Iomab-B arm or 28-42 days post start of CC. Pts not achieving CR/CRp could crossover (CO) to Iomab-B. Of 153 randomized pts, 100% of those who received a therapeutic dose of Iomab-B (n=66) underwent HCT vs 14 (18.2%) in the CC group. Among evaluable pts, dCR rates at 6 mos were 22% in the Iomab-B group vs 0% in the CC group (95% CI;12.29, 34.73; p<0.0001). A total of 37 pts with TP53 mutation were enrolled (CC=20; Iomab-B =17) with a prevalence of 24.2%. Baseline characteristics of these pts are shown in Table 1. The CR and dCR rates for Iomab-B treated pts were similar irrespective of TP53 mutation while in the CC group, no TP53 positive pts achieved CR or dCR (Table 2). Median overall survival (OS) for pts in the Iomab-B group, who were TP53 negative was 6.37 mos vs. 5.72 mos for the TP53 positive pts (HR=0.66; 95% CI [0.37, 1.18]; p=0.16). In the CC group (including CO pts), the median OS for TP53 positive pts was 2.96 mos. In a post hoc analysis of the CC group without CO, the median OS was 6.51 mos vs. 1.66 mos for the TP53 negative and positive groups respectively (HR=0.28; 95% CI [0.12, 0.67]; p=0.0022). For TP53 positive pts who received Iomab-B (Iomab-B + CO pts), the median OS was 5.49 mos vs. a median of 1.66 mos in pts who did not receive Iomab-B (CC pts without CO) [(HR=0.23; 95% CI [0.10, 0.52]; p=0.0002) (Figure 1)]. 131I-apamistamab led HCT significantly improves outcomes in pts with TP53 mutations, commensurate with rates observed in pts with wildtype TP53 in terms of CR, dCR and OS , overcoming the negative impact of this mutation. These data support the use of 131I-apamistamab led induction/conditioning and HCT in R/R AML, especially in patients with a TP53 mutation.
Authors: James Foran, Boglarka Gyurkocza, Rajneesh Nath, Hannah Choe, Mark R. Litzow, Camille Abboud, Nebu Koshy, Patrick J. Stiff, Benjamin Tomlinson, Sunil H. Abhyankar, Sameem Abedin, George L Chen, Zaid Al-Kadhimi, Partow Kebriaei, Mitchell Sabloff, Johnnie J. Orozco, Katarzyna Jamieson, Margarida Magalhaes-Silverman, Koen van Besien, Michael W Schuster, Arjun D. Law, Sebastian Mayer, Hillard M Lazarus, Jennifer Spross, Kate L Li, Norman G Nagl, Patrik Brodin, Madhuri Vusirikala, Akash Nahar, Prof. Brenda M. Sandmaier, John M. Pagel, Sergio A. Giralt, Avinash Desai, Stuart Seropian
Institutions: Mayo Clinic in Florida, Memorial Sloan Kettering Cancer Center, Banner MD Anderson Cancer Center, The Ohio State University, Mayo Clinic, Washington University in St. Louis, Louisiana State University, Louisiana State University Health Sciences Center Shreveport, Loyola University Medical Center, Loyola Medicine, University Hospitals Cleveland Medical Center, University Hospitals Seidman Cancer Center, University of Kansas Medical Center, Medical College of Wisconsin, Roswell Park Comprehensive Cancer Center, University of Alabama at Birmingham, The University of Texas MD Anderson Cancer Center, University of Washington, University of Iowa Hospitals and Clinics, University of Iowa Health Care, University of Iowa Holden Comprehensive Cancer Center, Stony Brook University Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W4391615289