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1506 Real-World Experience with CPX-351 for Secondary Acute Myeloid Leukemia: Comparison with FLAG-IDA in a Propensity Score Matching Analysis

Program: Oral and Poster Abstracts
Session: 617. Acute Myeloid Leukemias: Commercially Available Therapies: Poster I
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Diseases, Myeloid Malignancies
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Maria Agustina Perusini1, Claire Andrews, MBBCHBAO2*, Eshetu G Atenafu, MSc, PStat3*, Sarit E. Assouline, MD4, Joseph Brandwein, MD5, Mohammad Jarrar6*, Steven M. Chan, MD, PhD7, Signy Chow, MD, MSc, FRCPC8, Dina Khalaf9*, Vikas Gupta, MD, FRCP, FRCPath10, Dawn C. Maze, MD, FRCPC, MSc3, Mark D. Minden, MD, PhD3*, Gizelle Popradi11*, Waleed Sabry, MD, MSc. PhD, FRCPE12*, Lalit Saini13*, David Sanford, MD, FRCPC14, Lynn Savoie15*, Aaron Schimmer3*, Andre C. Schuh, MD, FRCPC3, Karen Yee, MD, FRCPC3* and Hassan Sibai, MD3

1Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
2St Vincents Hospital, Dublin, IRL
3Princess Margaret Cancer Centre / University Health Network, Toronto, ON, Canada
4Jewish General Hospital, McGill University, Westmount, QC, Canada
5Department of Medicine, University of Alberta, Edmonton, AB, Canada
6Windsor Regional Hospital, Windsor, Canada
7Princess Margaret Cancer Centre, Toronto, ON, Canada
8Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
9Juravinski Cancer centre, Hamilton, ON, Canada
10The Princess Margaret Cancer Centre, Toronto, ON, Canada
11McGill University Health Center, Montreal, Canada
12Saskatoon Cancer Centre, Saskatoon, SK, Canada
13London Health Sciences Centre, London, Canada
14Department of Medicine, Division of Hematology, University of British Columbia, Leukemia Bone Marrow Transplant Program of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada, Vancouver, Canada
15University of Calgary, Calgary, Canada

CPX-351 is approved for therapy-related acute myeloid leukemia (t-AML), and AML with myelodysplastic-related changes (AML-MRC). This approval was based on improved survival, remission rates, and similar safety compared to 7+3 regimen. In clinical practice, FLAG-IDA, followed by Allogenic Stem Cell transplant (ASCT) is an acceptable approach for this group of patients (pts). Evaluating real-world data on CPX compared to FLAG-IDA, and identifying which pts might benefit most from either treatment, is crucial for optimizing treatment decisions.

Aims

To report real-world outcomes of CPX vs FLAG-IDA in terms of Overall Survival (OS), Leukemia-free Survival (LFS), and complete remission (CR), and to determine if mutational profiles can predict responses.

Methods

Patients aged 18+ meeting WHO criteria for t-AML and AML-MRC with next-generation sequencing (NGS) profiles were included. Data were collected from 10 Canadian centers for CPX and the Princess Margaret Cancer Centre for FLAG-IDA. A total of 76 patients treated with CPX and 95 with FLAG-IDA were identified. Propensity Score Matching (PSM) was used to adjust for baseline differences between the two treatment groups. Key pre-treatment variables included: age, complex cytogenetics, and TP53 mutational status. PSM resulted in 92 pts (46 case-control pairs) with a caliper difference within 0.2.

Results

Significant differences between pts treated with different approaches were mitigated when PSM was applied. The median number of frequently detected somatic mutations was 2 (range: 1-8), with the most common mutations being RUNX1 (n=19), ASXL1 (n=20), DNMT3A (n=20), and TET2 (n=18).

In the PSM-selected population (n=92), the median follow-up time was 303 days (range: 22-1488). CR rates were higher with FLAG-IDA, with CR achieved in 27 (61%) pts treated with CPX-351 compared to 38 (82%) pts treated with FLAG-IDA (p=0.024). This finding did not translate into significantly higher rates of ASCT. Overall, 18 (41%) pts in the CPX group and 24 (52%) pts in the FLAG-IDA group proceeded with ASCT (p=0.28), corresponding to 55% and 52% of the pts who achieved CR1 after first induction (p=0.81).

Assessment of mutations and their biological pathways showed that pts with ASXL1 mutations had higher CR rates with FLAG-IDA (90%) compared to CPX (50%) (p=0.046). Activating signaling (AS) mutations also showed better CR rates with FLAG-IDA (100%) vs. CPX (70%) (p=0.04). The overall 1-year OS was 52.2% (95% CI: [40.5-62.6]). There were no significant differences in outcomes when comparing CPX with FLAG-IDA. For pts treated with CPX, the 1-year OS was 56.4% [39.6-70.2], compared to 49.4% [33.3-63.5] for those treated with FLAG-IDA (p=0.73, HR: 1.10 [0.60-2.1]). The 1-year LFS was 40% [25.6-55.4] for the CPX-351 group and 46.30% [30.8-60.5] for the FLAG-IDA group (p=0.59, HR: 0.86, [0.50-1.5]. When censoring OS for transplant, the 1-year OS was 52.8% [32.0-69.9] for CPX and 47.8% [23.9-68.4] for FLAG-IDA (p=0.55, HR: 0.79 [0.37-1.7].

Pts who underwent ASCT had significantly better OS (p=0.003). However, there was no significant OS difference between ASCT preceded by FLAG-IDA or CPX(p=0.08). Specifically, for pts who had ASCT, the 1-year OS was 78% [47.0-92.7] for CPX and 58% [35.0-75.9] for FLAG-IDA. Considering pts characteristics, type of mutations, or biological pathways involved, the only subgroup that demonstrated a difference in OS when comparing CPX with FLAG-IDA was the presence of tumor suppressor gene mutations (TS=TP53+PHF6, n=17). Pts with these mutations showed higher survival in the uni and multivariable analysis when treated with CPX; the 1-year survival rate for pts treated with CPX was 25% [3.7-55.8], compared to 13% [0.7-44] for those treated with FLAG-IDA (HR 3.11 [1.4-6.9], p<0.001). No other factors showed significant differences between treatments.

Conclusions

We used PSM to effectively minimize differences in pts characteristics. Although FLAG-IDA was associated with higher CR rates, particularly in pts with ASXL1 mutations and, AS mutations, this did not translate into higher ASCT rates, improved OS or LFS. The only subgroup that showed a difference in OS in favor of CPX was the one with TS gene mutations.These results should be interpreted with caution due to the small pt numbers. Data regarding the reasons for not proceeding with ASCT were not available. Future research will focus on expanding the cohort and evaluating adverse events

Disclosures: Assouline: BMS: Consultancy, Honoraria; F. Hoffman-La Roche Ltd.: Consultancy, Honoraria; Gilead: Honoraria; Ipsen: Consultancy; Novartis Canada Inc.: Research Funding; AstraZeneca: Consultancy, Honoraria; Genentech/Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Pfizer: Consultancy. Brandwein: AbbVie: Honoraria; Amgen: Honoraria; Astellas: Honoraria; Avir: Honoraria; BMS: Honoraria; Jazz: Honoraria; Paladin: Honoraria; Pfizer: Honoraria; Servier: Honoraria. Chan: Servier Pharmaceuticas LLC: Research Funding. Chow: Sobi: Consultancy, Honoraria, Other: supported travel. Gupta: Incyte: Consultancy, Other: Participation on a data safety or advisory board; Constellation: Consultancy; Sumitomo Pharm: Consultancy; Sierra Oncology: Consultancy, Other: Participation on a data safety or advisory board; CTI Biopharma: Consultancy, Other: Participation on a data safety or advisory board; Roche: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Other: Participation on a data safety or advisory board; BMS/Celgene: Consultancy, Other: Participation on a data safety or advisory board; GSK: Consultancy, Honoraria, Other: support for attending meetings and/or travel; Pfizer: Consultancy, Other: Participation on a data safety or advisory board; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy. 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. Popradi: Amgen: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Abbvie: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; BMS: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Daiichi Sankyo: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Gilead: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Jazz: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Kyowa Kirin: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Mallinckrodt: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Medexus: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Paladin: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Pfizer: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Sean Gen: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Sanofi: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Servier: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Sobi: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Takeda: Current Employment, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau. Sanford: AbbVie: Consultancy, Research Funding, Speakers Bureau; Astellas: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding. Schimmer: BMS: Research Funding; Jazz Pharmaceuticals: Consultancy; Medivir AB: Research Funding; Novartis: Consultancy; Otsuka: Consultancy; Takeda: Consultancy, Research Funding; UHN: Patents & Royalties. 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.

*signifies non-member of ASH