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2801 Clinical Characteristics and Outcomes of Mixed Phenotype Acute Leukemia (MPAL): A Large Multi-Center Retrospective Study

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Acute Myeloid Malignancies, AML, Adult, Clinical Research, Health outcomes research, Diseases, Lymphoid Malignancies, Myeloid Malignancies, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Adam Julian Cohen-Nowak, MD1*, Alexander Coltoff, MD2, Anand Ashwin Patel, MD3, Ehab L. Atallah, MD4, Mobachir El Kettani, MD5*, John Wang, MD1*, Emily Symes, MD6, Girish Venkataraman, MD, MBBS7, Alexa Siddon, M.D.8*, Emily Giever, MSN, RN9*, Rory M. Shallis, MD10, Jessica Altman, MD1, Kirsten Bell-Burdett1*, Talha Badar, MD11, Barina Aqil, MBBS1* and Yasmin Abaza, MD1

1Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
2Medical University of South Carolina, Charleston, SC
3Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
4Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI
5Yale Cancer Center, New Haven, CT
6Section of Hematology/Oncology, The University of Chicago, Chicago, IL, Chicago, IL
7Department of Pathology, University of Chicago, Chicago, IL
8Section of Hematology, Department of Medicine, Yale University School of Medicine, New Haven, CT
9Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
10Department of Internal Medicine, Section of Hematology, Yale School of Medicine - Yale Cancer Center, Killingworth, CT
11Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL

Introduction:

MPAL is a rare and heterogenous subtype of acute leukemia characterized by a single blast population with phenotypic expression of both myeloid and lymphoid lineages (biphenotypic) or multiple co-existing lineages of blasts that satisfy criteria for both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). MPAL presents both a diagnostic and therapeutic challenge given its rarity and resistance to traditional therapies. Data suggest ALL-directed or hybrid therapies are most effective at inducing durable remissions as a bridge to allogeneic stem cell transplantation (Allo-SCT; Lazzarotto 2023, Rasekh 2021); however, many are single-institution with limited sample sizes.

Methods:

A retrospective analysis at 7 US academic centers was performed. Adult patients (pts) with a confirmed diagnosis of MPAL between 2003-2023 were included. Comparisons of categorical and continuous variables utilized the Fisher exact test and Wilcoxon rank-sum or Kruskal-Wallis test as appropriate. Time-to-event outcomes were calculated using the Kaplan-Meier method and compared using log-rank test.

Results:

A total of 79 pts with MPAL were included in this study. Median age at diagnosis was 61 years (range, 18-89); 52% were ≥ 60 years. Majority of pts were male (60%), non-Hispanic white (64%), and had an ECOG ≤ 1 (83%). Of the 50 pts with baseline CSF analysis, 5 (10%) had CNS disease. Phenotypically, the predominant blast population was biphenotypic in 68%, myeloid in 17%, and lymphoid in 15% of cases. KMT2A-rearrangement and BCR::ABL1 translocation constituted 4% and 14% of cases, respectively, and 30% of pts had complex cytogenetics. Most common mutations at baseline included RUNX1 (33%), DNMT3A (30%), FLT3-ITD (26%), TET2 (19%), WT1 (19%), NRAS (18%), TP53 (17%), and ASXL1 (14%) mutations.

Of the 79 pts, 61 (77%) received intensive chemotherapy (IC), 12 (15%) received HMA-based regimens, 4 (5%) received other non-intensive regimens, and 2 (3%) transitioned to hospice prior to therapy. Among those receiving IC, 37 (61%) received ALL-directed therapies, 16 (26%) AML-directed, and 8 (13%) received hybrid regimens which included FLAG-VIPR (6/8), 7+3+vincristine (1/8), and cladrabine/low-dose cytarabine/vincristine/dexamethasone (1/8). Therapies were phenotype-discordant in 4/61 pts receiving IC; 3 myeloblast-predominant MPAL pts received ALL-directed therapy and one lymphoid-predominant pt received AML-directed therapy. Among 54 pts with predominant biphenotypic blasts, 52% received ALL-directed regimens. Of the 11 pts with BCR::ABL1 translocation, 8 (73%) received dasatinib, 2 (18%) ponatinib, and 1 (9%) received both. Only 30% of pts with FLT3-ITD mutated MPAL (5/17) received a FLT3 inhibitor.

Overall, 56% of pts achieved complete remission (CR) or CR with incomplete count recovery (CRi), with a median duration of response of 16.7 months (IQR: 8.1-46.1). The rates of CR/CRi were 39%, 56%, and 75% for myeloid, biphenotypic, and lymphoid MPAL, respectively. All pts with CNS disease (5/5) cleared after induction. Thirty-seven percent of pts proceeded with Allo-SCT in first remission (23% of myeloid pts, 58% lymphoid, 35% biphenotypic). Thirty-two percent of responders (CR/CRi; 14/44) relapsed with a median time to relapse of 9.4 months (range, 0.5-42).

Median overall survival (OS) for the entire cohort was 51 months (95% CI: 15-89). The 2-year OS rate was higher in pts with lymphoid-predominant phenotype (83%) compared to biphenotypic (55%) or myeloid-predominant phenotype (38%; p=0.16). Median OS was significantly longer in transplant versus non-SCT recipients (121 vs 14 months) with a 1-year OS rate of 97% vs. 59% (p<0.0001), respectively. Among pts who achieved CR/CRi, median OS significantly longer in transplant versus non-SCT recipients (121 vs 55 months, p=0.031), with a 2-year OS rate of 91% vs 75%.

Conclusions

In this large multi-center study, there were differences in survival based on predominant blast phenotype, with improved OS in lymphoid-predominant MPAL. Although most pts with biphenotypic-predominant MPAL received ALL-directed regimens, OS was worse in this subtype compared to lymphoid-predominant MPAL. There was significantly improved OS among Allo-SCT recipients underscoring the importance of Allo-SCT in this subtype of acute leukemia. Additional studies are needed to understand this rare and heterogenous disease.

Disclosures: Cohen-Nowak: AIDAR: Consultancy. Patel: Bristol Myers Squibb: Honoraria; Pfizer: Research Funding; Sobi: Honoraria; Sumitomo: Research Funding; AbbVie: Honoraria; Kronos Bio: Research Funding. Atallah: Novartis Pharmaceuticals Corporation: Honoraria. Shallis: Servier: Consultancy, Honoraria, Other: Steering Commitee; Rigel: Consultancy, Honoraria; Kura Oncology: Consultancy, Honoraria; Gilead Sciences, Inc: Consultancy, Honoraria. Altman: Rigel: Other: advisory board; Aptitude Health: Other: advisor; Gilead: Other: advisory board; VJ HemOnc: Other: advisory board and education; Treadwell Therapeutics: Other: advisory board; Dark Blue Therapeutics: Other: advisory board; Curio: Other: advisory board; Astellas: Honoraria, Other: advisory board, Research Funding; MD Educations: Other: advisory board and education; Daiichi Sankyo: Other: advisory board. Badar: Morphosys: Other: Advisory Board; pfizer: Other: Advisory board; Takeda: Other: advisory board .

*signifies non-member of ASH