Session: 617. Acute Myeloid Leukemias: Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Combination therapy, Adult, Clinical Research, Chemotherapy, Diseases, Treatment Considerations, Non-Biological therapies, Myeloid Malignancies, Study Population, Human
Methods: We analyzed a total of 1103 pts with newly diagnosed AML from across 4 large academic centers (DFCI, MSKCC, Yale and NCI in Lithuania) treated with 7+3 or CPX-351 (IC) v HMA+ven. vHRC was defined as AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2:MECOM(EVI1), t(3q26.2;v)/MECOM(EVI1)-rearranged, complex karyotype (CK) or monosomal karyotype (MK) as defined per 2022 ELN AML guidelines. Composite complete remission (cCR) was defined as CR+CR with incomplete count recovery (CRi). The Kaplan-Meier method was used to estimate OS and the log-rank test was used to compare OS between groups.
Results: A total of 318 pts (29%) had AML harboring vHRC with a median age of 66 yrs (range 18-93). Of these pts, 91% (n=289) harbored a CK, 64% (n=205) harbored a MK and 10% (n=32) had chr.3-related abnormalities. Pts were stratified into 2 groups based on treatment received: IC (n=137, 43%) or HMA+ven (n= 181, 57%). Pts in the HMA+ven group were older (median age: 72 yrs vs 59 yrs, p<.001) and more likely to harbor MK (75% vs 51%, p<.001). Pts in the IC group were more likely to harbor chr.3 abn (15% vs 6.6%, p=.023), whereas pts with CK-AML equally received IC and HMA+ven (88% vs 93%, p=.16). Pts who received HMA+ven were more likely to harbor a TP53 mutation (TP53mt) (70% vs 28%, p<.001), whereas those who received IC were more likely to harbor RAS pathway and secondary splicing mutations (59% vs 26%, p<.001 and 23% vs 14%, p=.043 respectively).
Of the total 318 pts, 280 (88%) were available for response assessment. cCR rates were higher with IC (66/127) than with HMA+ven (62/153) (52% vs 41%, p=.006). Among HMA+ven-treated pts, 41% (62/153) achieved a cCR as best response, 14% (22/153) attained morphologic leukemia-free state (MLFS) and 45% (69/153) had progressive disease (PD). Among pts treated with IC, 52% (66/127) achieved a cCR, 4% (5/127) MLFS and 44% (56/127) had PD. 77% (50/65) of HMA+ven pts experienced relapse vs 36% (35/96) of those treated with IC (p<.001). Significantly more pts proceeded to alloSCT after prior treatment with IC compared to HMA+ven (n=98, 53% vs 14% respectively, p<.001).
The mOS for the entire vHRC cohort was 8 mos (95% CI, 6.8-10) vs 29 mos (95%CI 24-42) for those with non-vHRC (p<.001). In the AML-vHRC population, pts treated with IC had a longer mOS than pts treated with HMA+ven [11 mos (95%CI, 8.6-18) vs 6.4 mos (95%CI, 5.2-8), p<.001]. Given that HMA+ven treated pts were older, we analyzed pts aged 60-75 yrs and found that mOS was similar between IC [7 mos (95%CI 5.6-11)] and HMA+ven [6.4 mos (95%CI 5.1-9.4)], p=0.56. Additionally, the mOS among pts who received an alloSCT did not differ by treatment strategy prior to transplantation [34 mos (95%CI, 21-64) for IC vs 39 mos (95%CI, 18-NR) for HMA+ven, p=0.71].
Given that >50% of pts with vHRC carried a TP53mt, we analyzed survival outcomes based on TP53mt status and treatment strategy. The mOS of pts with vHRC and concomitant TP53mt was 6.1 mos (95%CI 5.2, 7.8) and was similar between those treated with IC [7.6 mos (95%CI 4.1-11)] compared to HMA+ven [5.8 mos (95%CI 4.8-7.8)] (p=0.30). Conversely, the mOS of pts with vHRC without concomitant TP53mt was 12 mos (95%CI 8.3-18) and was higher among pts treated with IC [14 mos (95%CI 10-30)] compared to HMA+ven [8.0 mos (95%CI 5.2-15)] (p=.007).
Conclusion: In this large multicenter cohort, the survival for pts with AML-vHRC was overall poor. In pts aged 60-75, and in those who carried a TP53mt, or who underwent SCT following initial therapy, there was no significant difference in OS between those treated with HMA+ven and those treated with IC. In these pts, HMA+ven might be preferable given its comparatively lower toxicity, however, this should be explored ideally in a prospective setting.
Disclosures: Shallis: Servier: Consultancy, Honoraria, Other: Steering Commitee; Rigel: Consultancy, Honoraria; Kura Oncology: Consultancy, Honoraria; Gilead Sciences, Inc: Consultancy, Honoraria. Zucenka: AbbVie: Consultancy, Honoraria, Other: travel expenses; Astellas: Consultancy, Honoraria; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Other: travel expenses; Johnson & Johnson: Consultancy, Honoraria, Other: travel expenses; Takeda: Other: travel expenses. Garciaz: Janssen: Consultancy, Honoraria; Imcheck Therapeutics: Consultancy; Servier: Consultancy, Honoraria; Sanofi: Consultancy, Other: travel grant; Abbvie: Consultancy, Honoraria, Other: Travel grant; BMS: Consultancy. DeAngelo: Incyte: Consultancy; Fibrogen: Other: DSMB; MT Sinai MPN Consortium: Other: DSMB; Jazz: Consultancy; Kite: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Servier: Consultancy, Honoraria, Research Funding; Daiichi-Sankyo: Other: DSMB; Glycomimetics: Research Funding; Abvie: Research Funding; Takeda: Consultancy; Bristol-Meyers Squibb: Honoraria; Gilead: Consultancy; Curis: Consultancy; Blueprint: Consultancy, Research Funding; Autolos: Consultancy; Amgen: Consultancy, Honoraria. Stone: AbbVie: Consultancy. Luskin: Pfizer: Honoraria; Jazz: Honoraria; AbbVie: Research Funding; Novartis: Honoraria, Research Funding; KITE: Honoraria. Garcia: AbbVie: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Taiho: Research Funding; Servier: Consultancy; Newave: Research Funding. Chen: Rigel: Consultancy; AbbVie: Consultancy. Stein: Jazz Pharmaceuticals: Consultancy, Other: consulting fees; Gilead: Consultancy, Other: consulting fees; AstraZeneca: Consultancy, Other: consulting fees; Celgene: Consultancy, Other: consulting fees; Genentech: Consultancy, Other: consulting fees; Daiichi Sankyo, Inc.: Consultancy, Other: consulting fees; Servier: Consultancy, Other: consulting fees; Agios Pharmaceuticals: Consultancy, Other: consulting fees; Abbvie: Consultancy, Other: consulting fees; Astellas Pharmaceuticals: Consultancy, Other: consulting fees. Goldberg: Pfizer: Research Funding; Syndax Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Honoraria, Research Funding; Aprea: Research Funding; Aptose: Research Funding; AROG: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celularity: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Molecular Partners: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ikena Oncology: Consultancy; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Honoraria. Zeidan: Epizyme: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; BioCryst: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Kura: Consultancy, Honoraria, Research Funding; Keros: Consultancy, Honoraria; Hikma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Glycomimetics: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Geron: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Schroedinger: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Treadwell: Consultancy, Honoraria; Notable: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Sumitomo: Consultancy, Honoraria; Taiho: Consultancy, Honoraria; Faron: Consultancy, Honoraria; Chiesi: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Syros: Consultancy, Honoraria, Research Funding; Orum: Consultancy, Honoraria; Lava Therapeutics: Consultancy, Honoraria; Kyowa Kirin: Consultancy, Honoraria; Medus: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Syndax: Consultancy, Honoraria; Shattuck Labs: Research Funding; Vinerx: Consultancy, Honoraria; Astex: Research Funding; Rigel: Consultancy, Honoraria; Zentalis: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; ALX Oncology: Consultancy, Honoraria; Akeso Pharma: Consultancy, Honoraria. Stahl: GSK: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Sierra Oncolgy: Membership on an entity's Board of Directors or advisory committees; Kymera: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees.
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