131I-Apamistamab Effectively Achieved Durable Responses in Patients with R/R AML Irrespective of the Presence of Multiple High-Risk Factors
Authors: Seropian Stuart , Foran James M. , Gyurkocza Boglarka , Nath Rajneesh , Choe Hannah , Litzow Mark R. , Koshy Nebu , Stiff Patrick J. , Tomlinson Ben K. , Abhyankar Sunil , Abedin Sameem , Chen George , Al-Kadhimi Zaid , Kebriaei Partow , Sabloff Mitchell , Orozco Johnnie J. , Jamieson Katarzyna Joanna , Magalhaes-Silverman Margarida , Van Besien Koen , Schuster Michael W. , Law Arjun D. , Mayer Sebastian A. , Lazarus Hillard M. , Spross Jennifer , Li Kate L , Haeuber Elaina , Vusirikala Madhuri , Nahar Akash , Sandmaier Brenda M. , Pagel John , Giralt Sergio A. , Desai Avinash , Abboud Camille N. 
Published: December 2023

Background :

Most older patients (pts) with relapsed or refractory (R/R) AML cannot tolerate intensive treatment and are not eligible for curative allogeneic hematopoietic cell transplant (alloHCT). 131I-apamistamab, an anti-CD45 radioimmunoconjugate, delivers high dose targeted radiation to hematopoietic cells, allowing for myeloablation and eradication of leukemic cells while sparing toxicity to healthy organs. 131I-apamistamab led induction and conditioning can thus provide these pts with access to alloHCT.

Methods:

The SIERRA trial (NCT02665065) is a multi-center, randomized, controlled Phase 3 study comparing the rate of durable complete remission (dCR) lasting &gt;6 months (mos) after complete remission with/without platelet recovery (CR/CRp) between two groups: 131I-apamistamab led induction and conditioning followed by alloHCT vs physician's choice of conventional care (CC). Pts were randomized (1:1) to CC or 131I-apamistamab with fludarabine and total body irradiation (2 Gy) followed by alloHCT. CR/CRp assessment was 28-56 days post alloHCT or 28-42 days post initiation of therapy on the CC group. Pts in the CC group not achieving leukemia-free state could crossover (CO) to 131I-apamistamab. Here we report the results of a post hoc analysis to determine if the presence of various risk factors (i.e., Karnofsky Performance Status (KPS) &lt;90, HCT Comorbidity Index &gt;3, age &gt;65, adverse-risk cytogenetics, venetoclax failure prior to randomization) influenced achievement of dCR in pts treated with 131I-apamistamab.

Results:

In total, 153 pts were randomized (CC, n=76; 131I-apamistamab, n=77). All pts who received the therapeutic dose of 131I-apamistamab (n=66) underwent alloHCT vs 14 (18.2%) in the CC group. Of evaluable pts, dCR rates at 6 mos were 22% in the 131I-apamistamab group vs 0% in the CC group (95% CI;12.29, 34.73; p&lt;0.0001). A total of 19 pts (13, 131I-apamistamab group; 6, CO) achieved dCR. Table 1 shows the pt, disease, and transplant characteristics of dCR vs. non-dCR pts. Eight of the 19 pts (42.1%) had primary induction failure and the median time to randomization from diagnosis was 5.4 mos. Approximately 50% of pts (9/19) had adverse-risk cytogenetics. Over 35% (7/19) of the pts had failed prior venetoclax and the median number of prior treatments was 3 (range 1-5). A total of 10/19 (52%) pts had KPS of &lt;90% and a comorbidity index of &gt;3. There was no difference in the rate of dCR when stratifying by number of risk factors for a given pt (0 to 5) with 27% for pts with 0-1 risk factors, 14% for pts with 2-3 risk factors, and 11% for pts with 4-5 risk factors (p=0.251).

Conclusion:

Pts with R/R AML who have multiple risk factors such as adverse risk cytogenetics, age &gt;65, venetoclax failure, high comorbidity index or poor KPS are typically not considered for alloHCT due to high transplant-related mortality and post-transplant relapse rates. 131I-apamistamab was effective in achieving durable responses in R/R AML pts irrespective of the presence of multiple risk factors and successfully enabled alloHCT in such pts due to its targeted mechanism of action.