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 >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) <90, HCT Comorbidity Index >3, age >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<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 <90% and a comorbidity index of >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 >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.

Foran:BeiGene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Actinium: Research Funding; Kura: Research Funding; Sellas: Research Funding; Roivant: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Astellas: Research Funding; NCI: Membership on an entity's Board of Directors or advisory committees; CTI: Membership on an entity's Board of Directors or advisory committees. Gyurkocza:Actinium Pharmaceuticals, Inc: Research Funding. Nath:AlloVir: Membership on an entity's Board of Directors or advisory committees; Pfizer: Current equity holder in publicly-traded company; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Actinium Pharmaceuticals: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria. Choe:Actinium Pharmaceuticals: Other: Support for attending meetings and/or travel; MJH Life Sciences: Honoraria; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Receipt of equipment, materials, drugs to institution; Opna: Other: Receipt of equipment, materials, drugs to institution, Research Funding; NIH National Cancer Institute: Research Funding. Stiff:CRISPR: Consultancy; Amgen: Research Funding; AtaraBiotherapeutics: Research Funding; Eisai: Research Funding; Gamida Cell: Research Funding; Incyte Corp: Research Funding; Macrogenics: Research Funding; Takeda: Research Funding. Abedin:Incyte: Research Funding; AltruBio: Research Funding; Actinium Pharmaceutical: Research Funding; AbbVie: Consultancy, Honoraria; Daichii Sankyo: Consultancy, Honoraria; Servier: Consultancy, Honoraria. Kebriaei:Pfizer: Consultancy, Honoraria; Jazz: Consultancy, Honoraria. Sabloff:Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Taiho Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Actinium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees. Orozco:Actinium Pharmaceuticals: Other: Site PI for clinical trials sponsored by Actinium, Research Funding. Jamieson:Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Research Funding. Van Besien:Orca: Research Funding; Precision Biosciences: Research Funding; Avertix: Current equity holder in private company; Calibr: Research Funding; BMS: Research Funding; Actinium: Research Funding; Moprhosys: Consultancy; Intellia: Consultancy; Hemogenyx: Consultancy, Current equity holder in publicly-traded company; SNIPR: Consultancy; Incyte: Consultancy. Schuster:Abbvie: Consultancy, Speakers Bureau; Actinium: Research Funding; AlloVir: Research Funding; Amgen: Other: Stock, Speakers Bureau; Astellas: Speakers Bureau; Beigene: Speakers Bureau; BMS: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Epizyme: Speakers Bureau; Genentech: Speakers Bureau; GSK: Research Funding; Incyte: Research Funding; Janssen: Consultancy, Speakers Bureau; MorphSys: Research Funding, Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau; Rafael: Research Funding; Seattle Genetics: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; ADC Therapeutics: Other; CTI Biopharma Corp: Speakers Bureau; Karyopharm: Research Funding, Speakers Bureau; Macrogenomics: Research Funding; Pfizer: Consultancy, Research Funding; Sanofi: Speakers Bureau; Syndax Pharmaceuticals: Research Funding. Law:Actinium Pharmaceuticals: Research Funding. Mayer:Omeros: Consultancy. Lazarus:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Spross:Actinium Pharmaceuticals: Current Employment. Li:Actinium Pharmaceuticals: Current Employment. Haeuber:Actinium Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Vusirikala:Actinium Pharmaceuticals: Current Employment. Nahar:Actinium Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Sandmaier:Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Pagel:Loxo Oncology at Lilly: Current Employment. Giralt:Amgen, Actinuum, Celgene/BMS, Omeros, Johnson & Johnson, Miltenyi, Takeda: Research Funding; Amgen, Actinuum, Celgene/BMS, Kite Pharma, Janssen, Jazz Pharmaceuticals, Johnson & Johnson, Novartis, Spectrum Pharma, Takeda: Membership on an entity's Board of Directors or advisory committees. Desai:Actinium Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company.

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2023
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