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5193 What Is the Prognostic Relevance of Responses Less Than a CR(Sub-CR) to Initial AML Treatment?

Program: Oral and Poster Abstracts
Session: 908. Outcomes Research: Myeloid Malignancies: Poster III
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Diseases, Myeloid Malignancies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Akhil Rajendra, MD, MBBS, DM1, Elliot Smith, MD2*, Eshetu Atenafu, M.Sc, P. Stat3*, Aniket Bankar, MD, MBBS, MSc, DM4, Steven M. Chan, MD, PhD5, Marta Beata Davidson, MD, PhD4, Vikas Gupta, MD, FRCP, FRCPath6, Mark D. Minden, MD, PhD7*, Maria Agustina Perusini8, Guillaume Richard-Carpentier, MD, FRCPC9, Aaron D Schimmer, MD10, Andre C. Schuh, MD, FRCPC7, Hassan Sibai, MD7, Karen Yee, MD, FRCPC7* and Dawn C. Maze, MD, FRCPC, MSc7

1Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
2Department of Medicine, University of Toronto, Toronto, ON, Canada
3Biostatistics, University Health Network, Toronto, Canada
4Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
5Princess Margaret Cancer Centre, Toronto, ON, Canada
6The Princess Margaret Cancer Centre, Toronto, ON, Canada
7Princess Margaret Cancer Centre / University Health Network, Toronto, ON, Canada
8Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
9Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
10Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada

Context: Achievement of CR has long been one of the goals of AML treatment. Over the years, less stringent criteria for defining CR (sub-CR) have been developed to incorporate patients in clinical trials and to facilitate regulatory approvals. In both the intensive and non-intensive up-front treatment scenarios, sub-CR responses are associated with inferior outcomes compared to those achieving true CR. However, it is not clear whether sub-CR response comprises a prognostic factor independent of the underlying disease biology.

Design: Retrospective single center study

Patients and methods: 363 AML patients CR or sub-CR response between Jan 2019 to Jan 2023 were included. Sub-CR responses included CRi, CRh, and MLFS per ELN 2022. Univariate and multivariable logistic regression models were conducted to assess the association between clinical variables and CR/sub-CR response. Kaplan-Meier curves were generated for EFS and OS, and differences were tested using the log-rank test. All statistical analyses were performed using the EZR software (a modified version of R commander (version 1.5.4)).

Objectives: Primary objective: To identify predictors of sub-CR response.

Secondary objectives: To compare EFS and OS between CR and sub-CR patients, in both overall population and AML subgroups

Results: Among the 363 patients, 227 patients achieved CR, and 136 sub-CR. Sub-CR responses included CRi/h(75) and MLFS(61). By UVA, sub-CR response was associated with secondary AML(OR: 2.801(95%CI[1.70 - 4.63]); p<0.0001), adverse cytogenetics(OR: 5.008[1.36 - 18.35]; p 0.02), intermediate cytogenetics(OR: 6.5[1.92 - 22.03]; p 0.02), ELN adverse risk(OR: 5.95[3.2 – 11.1]; p<0.001), ELN intermediate risk(OR: 2.11[1.07 - 4.15]; p<0.0001), unmutated NPM1 (OR: 1.96[1.23 – 3.13]; p 0.02), MDS-related mutations(OR: 4.49[2.84 - 7.09]; p<0.0001) and non-intensive treatment (OR: 8.612[4.98 - 14.87]; p<0.001). On MVA, sub-CR responses were associated with non-intensive treatment (OR: 6.273 [3.46 - 11.35]; p<0.0001), ELN adverse risk (OR: 3.033 [1.49 - 6.18]; p 0.0073) and MDS-related mutations (OR: 2.757[1.57 - 4.83]; p 0.0004).

The 24 month-EFS was inferior(p<0.0001) in patients with sub-CR (33.5% [25.2 - 41.7]) compared those with a CR (58.1% [51.1 - 64.5]). Similarly, 24-month OS was inferior in the sub-CR group (45.3% [36.3 - 53.9] (sub-CR) vs 67.5% [60.6 - 73.5] (CR); p<0.0001). This difference persisted after censoring for transplant (HSCT) (26.4% [17.6 - 36.1] (sub-CR) vs 54.6% [45.9 - 62.6] (CR); p<0.0001).

The inferior OS of the sub-CR group was seen in ELN favorable (24-month OS: 56.2%(sub-CR) vs 84.3%(CR); p 0.008) and intermediate risk (24-month OS: 52.9%(sub-CR) vs 64.9%(CR); p-0.02), but not in adverse risk (24-month OS: 39.8%(sub-CR) vs 52.3%(CR); p-0.187). Inferior OS of sub-CR was observed in intensively treated patients (24-month OS:52.7%(sub-CR) vs 71.7%(CR); p-<0.0001), but not in non-intensively treated patients (24- month OS: 37.6%(sub-CR) vs 22.5%(CR); p-0.149).

When MRD status was considered, we did not observe a significant difference in the 24-month OS between sub-CR and CR, whether MRD negative (24-month OS: 56.6%(sub-CR) vs 67.7%(CR); p-0.06) or positive (24-month OS: 40.3%(sub-CR) vs 62.95(CR); p-0.08). In patients who underwent HSCT, there was no significant difference in the 24-month OS between sub-CR and CR (64%(sub-CR) vs 72.4%(CR); p-0.0504) whereas a difference was noted in the non-transplanted population (31.6%(sub-CR) vs 62.5%(CR); p-<0.0001).

Conclusions: We conclude that sub-CR responses in AML reflect both underlying disease biology and type of treatment administered. Sub-CR responses were more common in patients with adverse pre-treatment characteristics (ELN adverse risk and MDS-related mutations), and in non-intensively treated patients. In these subgroups, a sub-CR response did not confer inferior survival. In contrast, sub-CR response was associated with inferior survival in intensively treated patients and in favorable/intermediate risk AML. The OS effects of sub-CR response were MRD independent in our hands, and HSCT appeared to be able to overcome the negative OS impact of sub-CR status.

Disclosures: Chan: Servier Pharmaceuticas LLC: Research Funding. Gupta: Sierra Oncology: Consultancy, Other: Participation on a data safety or advisory board; GSK: Consultancy, Honoraria, Other: support for attending meetings and/or travel; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Other: Participation on a data safety or advisory board; Sumitomo Pharm: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Consultancy, Other: Participation on a data safety or advisory board; Constellation: Consultancy; Pfizer: Consultancy, Other: Participation on a data safety or advisory board; BMS/Celgene: Consultancy, Other: Participation on a data safety or advisory board; Daiichi Sankyo: Consultancy, Other: Participation on a data safety or advisory board; Novartis: Consultancy. Richard-Carpentier: Taiho: Honoraria, Other: Advisory Board Participation; AbbVie: Honoraria, Other: Advisory Board Participation; BMS: Other: Advisory Board Participation; Astellas: Honoraria, Other: Advisory Board Participation; Pfizer: Honoraria, Other: Advisory Board Participation. Schimmer: Jazz: Consultancy; Otsuka Pharmaceuticals: Consultancy; Novartis: Consultancy; UHN: Patents & Royalties: DNT cells; Medivir AB: Research Funding; BMS: Research Funding; Takeda: Consultancy, Research Funding. Yee: Astex: Other: research support; Forma Therapeutics: Other: research support; F. Hoffmann-La Roche: Other: research support; Genentech: Other: research support; Geron: Other: research support; Gilead Sciences: Other: research support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: research support; Bristol Myers Squibb/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Taiho Pharma: Membership on an entity's Board of Directors or advisory committees; Taiho Pharma: Honoraria. Maze: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma Essentia: Research Funding; Takeda: Research Funding; Kronos Bio: Research Funding; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy.

*signifies non-member of ASH