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2749 Association of Hypometilating Agents (HMA) + Venetoclax (VEN) in the Treatment of Myeloproliferative Neoplasms in Blastic Phase (MPN-BP) and Acute Leukemias Evolved from Myelodysplastic Syndromes (AML-MDS) Already Treated with Azacytidine

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Combination therapy, Diseases, Therapies, Adverse Events, Myeloid Malignancies
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Roberto Latagliata, MD1*, Gianluca Cristiano, MD2*, Dorela Lama, MD3*, Susanna Fenu, MD4*, Lorenzo Rizzo, MD5*, Benedetta Cambò, MD6*, Simone Zoletto, MD7*, Francesca Spirito, MD8*, Fabrizio Cavalca9*, Daniele Cattaneo, MD10*, Natalia Cenfra, MD11*, Giulia De Luca, MD12*, Beatrice Esposito Vangone, MD13*, Ambra Di Veroli, MD1*, Raffaele Palmieri, MD14*, Mario Annunziata15*, Olga Mulas, MD16*, Elisabetta Abruzzese, MD17, Alfredo Molteni, MD18*, Monica Piedimonte19*, Ida Carmosino, MD20*, Prassede Salutari, MD21*, Annalisa Biagi, MD22*, Monica Bocchia, MD23*, Michelina Santopietro, MD24*, Gianni Binotto, MD25*, Alessandra Iurlo, MD, PhD26*, Monica Crugnola, MD27*, Marta Riva, MD28*, Anna Lina Piccioni, MD29*, Elena Maria Elli, MD30*, Antonio Curti, MD, PhD31 and Antonella Poloni, PhD, MD32*

1Hematology, Belcolle Hospital, Viterbo, Italy
2Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
3Hematology, AOU Ospedali Riuniti, Università Politecnica Marche, Ancona, Italy
4Hematology Dep. Az. Osp. San Giovanni-Addolorata Rome, Italy, Rome, Italy
5Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
6Hematology and BMT Unit, Azienda Ospedaliera-Universitaria di Parma, Parma, Italy
7Department of Medicine, Hematology and Clinical Immunology, University of Padua, Padua, Italy
8Haematology and Haematopoietic Stem Cells Transplant Unit, AO San Camillo-Forlanini, Rome, Italy
9Hematology Division and Bone Marrow Transplant Unit, San Gerardo Hospital, Monza, Italy
10Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
11Hematology Unit, S. Maria Goretti Hospital, AUSL Latina, Latina, ITA
12UOC Hematology, Santo Spirito Hospital, Pescara, Italy
13UOC Hematology, Università di Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy
14Hematology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
15Hematology, San Giuseppe Moscati Hospital, Aversa, Italy
16Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
17Hematology, S. Eugenio Hospital, Tor Vergata University, ASL Roma2, Roma, I, Italy
18Division of Hematology, ASST Cremona, Cremona, Italy
19Hematology, "Sant'Andrea" Hospital-Sapienza, University of Rome, Department of Clinical and Molecular Medicine,, Roma, ITA
20Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
21Dipartimento Oncologia Ematologia, Ospedale Civile Spirito Santo, Pescara, Italy
22Hematology, Santa Maria Goretti Hospital – Polo Pontino “Sapienza” University, Latina, Italy
23Hematology, University of Siena, Azienda Ospedaliera Universitaria Senese, Siena, Italy, Siena, Italy
24U.O. di Ematologia e Trapianti di cellule Staminali. A.O.S. S. Camillo-Forlanini, Rome, Italy
25Department of Medicine, Hematology and Clinical Immunology, Padua School of Medicine, Padua, Italy
26Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
27Hematology and BMT Center, Department of Medicine and Surgery, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
28Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, MI, Italy
29Hematology, San Giovanni Hospital, Rome, ITA
30Hematology Division and Bone Marrow Transplant Unit. San Gerardo Hospital, ASST Monza, Monza, Italy
31Department of Hematology and Oncology Institute of Hematology L. e A. Seràgnoli, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Italy
32Hematology, Università Politecnica delle Marche - AOU Ospedali Riuniti, Ancona, ITA

Background Association of hypometilating agents (HMA) and venetoclax (VEN) is widely used in the treatment of elderly patients with de novo Acute Myeloid Leukemia (AML) not eligible for intensive chemotherapy, with improvement of survival. However, very few data are available about the use of this combined regimen in patients with Myeloproliferative Neoplasms evolved in blastic phase (MPN-BP) and in patients with AML secondary to Myelodysplastic Syndrome (AML-MDS) previously treated with HMA during the dysplastic phase. In both these settings the survival is dismal and at present no therapy seems to have a role.

Methods Data of patients with MPN-BP and AML-MDS treated frontline with HMA+VEN in 20 hematological Italian Centers outside clinical trials were retrospectively collected and analysed. Patients treated with HMA + VEN as salvage therapy after induction failure/relapse were excluded. Composite overall response rate [ORR; complete remission (CR) + CR with incomplete hematologic recovery (iCR) + partial remission (PR) + hematological improvement (HI)], duration of response and overall survival (OS) were assessed.

Results: A total of 64 patients (41 MPN-BP and 23 AML-MDS) treated between 11/2018 and 5/2022 were included. Baseline characteristics at evolution and starting treatment for the whole cohort and according to previous disease are reported in the Table 1. Median interval from initial MPN/MDS diagnosis to evolution was 31.5 months [interquartile range (IQR) 16.0 – 108.1] in the entire cohort [42.0 months (IQR 22.0 – 124.9) in MPN-BP and 18.8 months (IQR 10.9 – 39.8) in AML-MDS]. Patients were treated for a median of 2 courses (IQR 2-6): HMA were administered at standard dosage, VEN daily dose in the 1st cycle was 50 mg in 6 patients (9.4%), 100 mg in 27 patients (42.2%), 200 mg in 8 patients (12.5%) and 400 mg in 23 patients (35.9%), respectively. On the whole, 50/64 patients (78.1%) had at least one hematological toxicity of grade 3-4: in particular, severe neutropenia (PMN < 0.5 x 109/l) was reported in 46 patients (71.8%). Twenty-nine patients (45.3%) had at least one infective episode during the treatment: pulmonary infections were reported in 18 patients (28.1%). Response to treatment is shown in the Table 1: ORR was 60.0% (60.5% in MPN-BP and 59.1% in AML-MDS, respectively). Median response duration of the whole cohort was 5.3 months (95%CI 2.2-8.4), without significant differences in MPN-BP and AML-MDS patients [4.8 (95%CI 3.2 – 6.5) and 7.8 (95%CI 2.8 – 12.8) months, respectively (p=0.467)]. After a median follow-up of 6.1 months (IQR xx – xx) from the start of combined regimen, 37 patients (57.8%) died, 2 (3.1%) were lost to follow-up and 25 (39.1%) were alive. Median overall survival (OS) of the whole cohort was 7.2 months (95%CI 4.8-9.7), without differences between MPN-BP and AML-MDS groups [8.0 (95%CI 5.0 – 10.9) and 6.8 (95%CI 4.3 – 9.3) months, respectively (p=0.717, Figure 1)]. Patients with any type of response to the combination regimen had a significantly longer OS compared to patients with progressive/stable disease [11.6 (95%CI 8.2 – 14.9) and 5.4 (95%CI 2.8 – 7.9) months, respectively (p=0.006)].

Conclusions: Our real-life data confirm that HMA + VEN combination could have a role in these two very challenging subsets of secondary AML, with achievement of ORR > 50% in patients unfit for intensive approaches: however, this treatment is affected by severe hematological and infective toxicities and the response duration is short, leading to a persistently poor median OS. Larger cohorts of patients and a longer follow-up are needed to assess factors predictive of CR/iCR achievement, while the addition of other targeted therapies should be explored.

Disclosures: Latagliata: BMS: Honoraria; Novartis: Honoraria. Abruzzese: BMS, Incyte, Novartis, Pfizer: Consultancy. Binotto: Novartis, BMS, Incyte, Pfizer: Honoraria. Crugnola: Amgen: Speakers Bureau; Novartis: Speakers Bureau. Curti: Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH