Association of Hypomethylating Agents + Venetoclax in the Real-Life Treatment of Myeloproliferative Neoplasms in Blastic Phase

Latagliata, Roberto

Oral and Poster Abstracts
634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I

MPN, Combination therapy, Chronic Myeloid Malignancies, Diseases, Therapies, Myeloid Malignancies, Human, Study Population

Roberto Latagliata¹^*, Gianluca Cristiano, MD²^*, Dorela Lame, MD³^*, Alda Strazimiri, MD⁴^*, Fabrizio Cavalca⁵^*, Lorenzo Rizzo, MD⁶^*, Giulia De Luca, MD⁷^*, Simone Zoletto, MD⁸^*, Vincenzo Federico, MD⁹^*, Daniele Cattaneo, MD¹⁰^*, Annalisa Biagi, MD¹¹^*, Monica Crugnola, MD¹²^*, Pasquale Niscola, MD¹³^*, Raffaele Palmieri, MD¹⁴^*, Anna Lina Piccioni, MD¹⁵^*, Olga Mulas, MD¹⁶^*, Beatrice Esposito Vangone, MD¹⁷^*, Michelina Santopietro, MD¹⁸^*, Ida Carmosino, MD¹⁹^*, Alessandra Iurlo, MD, PhD²⁰^*, Nicola Di Rienzo, MD²¹^*, Gianni Binotto, MD²²^*, Prassede Salutari, MD²³^*, Marta Riva, MD²⁴^*, Massimiliano Bonifacio, MD²⁵^*, Elena Maria Elli, MD²⁶^*, Antonio Curti, MD, PhD²⁷ and Antonella Poloni, MD²⁸^*

¹Hematology, Belcolle Hospital, Rome, Italy
²Department of Medical and Surgical Sciences, Institute of Hematology "L. and A. Seràgnoli", University of Bologna, Bologna, Italy
³Hematology, AOU Marche - Politecnic University Marche, Ancona, Italy
⁴Department of Engineering for Innovation Medicine, Section of Innovation Biomedicine, Hematology Area, University of Verona, Verona, Italy
⁵Hematology Department, San Gerardo Hospital, Monza, Italy
⁶Department of Hematology and Oncology, Niguarda Cancer Center, ASST Ospedale Nig, Milan, Illinois, ITA
⁷UOC Ematologia Clinica, Ospedale Civile "Santo Spirito", Pescara, Italy
⁸Hematology Unit, Department of Medicine, University of Padova, Padova, Italy
⁹Hematology, Vito Fazzi Hospital, Lecce, Italy
¹⁰Hematology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
¹¹S.M. Goretti Hospital – Polo Pontino “Sapienza” University - Latina, Latina, Italy
¹²Hematology Unit and BMT, University Hospital of Parma, Parma, Italy
¹³Hematology Unit, Sant'Eugenio Hospital, Rome, Italy
¹⁴Department of Onco-Hematology, Fondazione Policlinico Tor Vergata, Rome, Italy
¹⁵Dipartimento di Ematologia, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy
¹⁶Department of Medical Sciences and Public Health, University of Cagliari, Businco Hospital, Cagliari, Italy
¹⁷UOC Ematologia, Azienda ospedaliero-universitaria Senese, Siena, Italy
¹⁸Hematology and Hematopoietic Stem Cells Transplant Unit, AO San Camillo-Forlanini, Rome, Italy
¹⁹Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
²⁰Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
²¹UO EMATOLOGIA, ASL LECCE, OSPEDALE V. FAZZI, Lecce, Italy
²²Department of Medicine, Hematology and Clinical Immunology, University of Padua, Padua, Italy
²³Department of Hematology, Ospedale Civile Spirito Santo, Pescara, Pescara, Italy
²⁴Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda Cancer Center, Milano, Italy
²⁵Department of Medicine, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy
²⁶Fondazione IRCCS, San Gerardo dei Tintori, Monza, Monza, Italy
²⁷IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy
²⁸Hematology, AOU Marche - Politecnic University Marche - Ancona, Ancona, ITA

Background Association of hypomethylating agents (HMA) and venetoclax (VEN) is widely used in elderly patients (pts) with de novo Acute Myeloid Leukemia not eligible for intensive chemotherapy, with improvement of survival. However, very few data are available in pts with Myeloproliferative Neoplasms evolved in blastic phase (MPN-BP). In this setting, the survival is dismal and at present no therapy seems to have a role.

Methods Data of 54 pts with MPN-BP treated frontline with HMA+VEN in 19 hematologic Centers in Italy outside clinical trials from 11/2018 to 3/2023 were retrospectively collected and analysed. Composite overall response rate [ORR; complete remission (CR) + CR with incomplete hematologic recovery (iCR) + partial remission (PR) + hematologic improvement (HI)], duration of response and overall survival (OS) were assessed.

Results: Baseline features at evolution and starting treatment are reported in the Table. Median interval from initial MPN diagnosis to evolution was 38.4 months [interquartile range (IQR) 15.4–124.5]. Pts were treated for a median of 3 courses (IQR 2-7): HMA were administered at standard dosage, VEN daily doses in the 1^st cycle are reported in the Table. On the whole, 40 pts (74.1%) had at least one hematologic toxicity of grade 3-4: in particular, severe neutropenia (PMN < 0.5 x 10⁹/l) was reported in 37 pts (68.5%). Thirty pts (55.5%) had at least one infective episode during the treatment: pulmonary infections were reported in 13 pts (24.0%). Response to treatment is shown in the Table: ORR was 62.7%, with a median response duration of 9.4 months (95%CI 5.8-12.9). After a median follow-up of 6.7 months (IQR 3.2–12.1), 35 pts (64.8%) died, 2 (3.7%) were lost to follow-up and 17 (31.5%) were alive. Median OS of the whole cohort was 10.6 months (95%CI 5.8-15.3), Pts with any response to HMA+VEN had a significantly longer OS compared to pts with progressive/stable disease [11.6 (95%CI 9.4–13.7) versus 5.4 (95%CI 2.1–8.6) months, respectively (p=0.002)] (Figure).

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

Disclosures: Latagliata: Celgene: Honoraria; Novartis: Honoraria; Janssen: Honoraria; BMS: Honoraria. Cattaneo: Novartis, Pfizer, Incyte, BMS, GSK: Honoraria. Palmieri: Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Iurlo: Novartis, Pfizer, Incyte, BMS, GSK, AOP Health: Honoraria. Bonifacio: BMS: 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; Clinigen: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Elli: BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Curti: Pfizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

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1842 Association of Hypomethylating Agents + Venetoclax in the Real-Life Treatment of Myeloproliferative Neoplasms in Blastic Phase