131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant for Patients with TP53 Mutated R/R AML Results in Significantly Improved Outcomes

Background 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. Methods 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. Results 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)]. Conclusion 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.