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2868 Outcomes of Blast-Phase MPN and JAK2, MPL, and CALR Mutated de Novo AML Compared to AML with Wild-Type JAK2, MPL, and CALR Genes: A Propensity Score-Adjusted Cohort Study

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Diseases, Myeloid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Daniel P. Nurse, DO1, Jessica El-Asmar, MD, MPH2, Ameed Bawwab, MD3*, Yomna Abu-Farsakh, MD4*, Moath Albliwi, MD5*, John Hanna, MD5, Asad Rauf5*, Hasan Abuamsha5*, Heya Batah, MD5*, Daniel Cancilla, MD5*, Emily C. Zabor, DrPH6*, Yohana B. Bedelu6*, Mark Jinan Chen, PhD7*, Joy Nakitandwe, PhD7*, Ismail Elbaz Younes, MD8*, David S. Bosler, MD7*, Akriti G. Jain, MD2, John C. Molina, MD, MEd2, Sophia Balderman, MD2*, Abhay Singh, MD, MPH2, Aaron T. Gerds, MD, MS2, Sudipto Mukherjee, MD, PhD, MPH2, Anjali S. Advani, MD2, Hetty E. Carraway, MD, MBA2 and Moaath K. Mustafa Ali, MD, MPH2

1Department of Internal Medicine, Cleveland Clinic, University Heights, OH
2Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
3Department of Internal Medicine, Cleveland Clinic, Akron, OH
4Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, North Canton, OH
5Department of Internal Medicine, Cleveland Clinic, Cleveland, OH
6Department of Quantitative Health Sciences, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
7Department of Pathology and Laboratory Medicine, Cleveland Clinic Diagnostics Institute, Cleveland, OH
8Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis

Background:

The BCR-ABL-negative myeloproliferative neoplasms (MPNs) include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. These MPNs are clonal disorders of hematopoietic stem cells that can transform into secondary acute myeloid leukemia (AML), known as the blast phase of an MPN. Transformation to blast phase occurs in about 10% of patients with MPN. Previous studies have shown that patients with MPN-BP have very poor prognosis, and there is currently no accepted standard of care for these patients. The VIALE-A trial, which showed that combining venetoclax (VEN) with azacitidine improved outcomes in AML patients, excluded patients with MPN-BP. The purpose of this single-center retrospective study is to compare the outcomes of MPN-BP patients to patients with de novo AML with JAK2, MPL, and CALR mutations and AML with wild-type JAK2, MPL, and CALR genes.

Methods:

We conducted a single-center retrospective cohort study to compare composite complete response (CCR), overall survival (OS), and event-free survival (EFS) of patients with MPN-BP, de novo AML with underlying JAK2, MPL, or CALR mutations (AML-D-MPN), and AML without underlying JAK2, MPL, or CALR mutations (AML-WT). Patients with AML who were tested for JAK2, MPL, and CALR mutations at baseline were included in the study. Data collected included age, gender, ethnicity, comorbidities, AML subtypes, cytogenetics, BCR::ABL1 and FLT3 status, mutational profiles (via next-generation sequencing), ECOG performance status, treatment history, and follow-up. CCR was defined as complete response (CR) or CR with incomplete count recovery. Event-free survival (EFS) was defined from the diagnosis date to refractoriness, progression, or death. Overall survival (OS) was from diagnosis date to death. Survival probabilities were estimated using the Kaplan-Meier method, with differences assessed by the log-rank test. Multivariable regression and propensity score (PS) analysis were used to adjust for confounders, including comorbidities.

Results:

From May 2017 to September 2023, 730 AML patients were treated at the Cleveland Clinic Foundation, Ohio. Of the 528 AML patients who had NGS at baseline, 74 had MPN-BP (14%), 22 had AML-D-MPN (4%), and 432 had AML-WT (82%). The median age for the groups above were 62 (IQR: 55-73), 71 (IQR: 66-78), and 66 (IQR: 57-73) years. In patients with MPN-BP, 70% had JAK2 mutations, 28% had CALR mutations, and 2% had MPL mutations. In patients with AML-D-MPN, 100% had JAK2 mutations. The median time for MPN to BP transformation was 49 months (IQR: 21-123). With a median follow-up of 34.9 months (mo) (95CI: 1.8-90.2), the median OS for MPN-BP was 7.1 mo (95CI: 4.1-11), 13 mo (95CI: 6.1-NC) for AML-D-MPN, and 12 mo (95CI: 10-14) for AML-WT (log-rank P<0.01). Similarly, the MPN-BP had worse EFS when compared to AML-D-MPN and AML-WT (P=0.02).

In a combined analysis for MPN-BP and AML-D-MPN, we compared CCR, OS and EFS between first-line treatment arms. Twenty-seven patients received intensive regimens, 17 received VEN + hypomethylating agents (HMA), 11 received HMA, and 22 received other regimens. There was no statistically significant difference in response rate on PS-adjusted logistic regression. The PS-adjusted median OS was 17 mo (95CI: 11-NR) for intensive regimens, 10 mo (95CI: 5.2-NR) for VEN+HMA, 13 mo (95CI: 13-13) for other regimens and 1.2 mo (95CI: 0.85-NR) for HMA regimens. Similarly, the PS-adjusted median EFS was 13 mo (95CI: 407-NR) for intensive regimen, 5.2 mo (95CI: 4.2-NR) for VEN+HMA regimens, 5.1 mo (95CI: 5.1-5.1) for other regimens and 1.2 mo (95CI: 0.85-NR) for HMA regimens.

Conclusions:

While all AML patients in our study had poor survival outcomes, patients with MPN-BP had worse survival when compared to patients with de novo AML with a similar mutational profile and patients with AML negative for these mutations. Intensive regimens in MPN-BP and AML-D-MPN were associated with the largest impact on OS and should be utilized when feasible.

Disclosures: Jain: Rigel: Other: Teaching and Speaking. Molina: Autolus: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Gerds: Agios: Consultancy; Disc Medicine: Consultancy; PharmaEssentia: Consultancy; Rain Oncology: Consultancy; GSK: Consultancy; AbbVie: Consultancy; BMS: Consultancy. Advani: Incyte: Research Funding; OBI: Research Funding; Seattle Genetics: Research Funding; Amgen: Research Funding; Wolters Kluwer: Honoraria; Wiley: Honoraria; Springer: Honoraria; American Society of Hematology: Honoraria; PER: Honoraria; MD Education: Honoraria; Emmes: Honoraria; Macrogenics: Research Funding; MJH Life: Honoraria; Web MD: Honoraria; Pfizer: Other: Manuscript help, Research Funding; Glycomimetics: Research Funding; BEAM: Other: Research support, Research Funding; Immunogen: Research Funding; Kite: Consultancy, Research Funding; Servier: Research Funding; Kura: Research Funding; Novartis: Consultancy. Carraway: Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Stemline: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi: Membership on an entity's Board of Directors or advisory committees. Mustafa Ali: Daiichi Sankyo: Consultancy.

*signifies non-member of ASH