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Clinical Trial
. 2025 Jan 1;131(1):e35662.
doi: 10.1002/cncr.35662. Epub 2024 Nov 25.

Long-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia

Wei-Ying Jen  1 , Jennifer Marvin-Peek  1 , Hagop M Kantarjian  1 , Yesid Alvarado  1 , Gautam Borthakur  1 , Elias Jabbour  1 , William Wierda  1 , Tapan M Kadia  1 , Naval G Daver  1 , Courtney D DiNardo  1 , Nicholas J Short  1 , Nitin Jain  1 , Alessandra Ferrajoli  1 , Steven Kornblau  1 , Musa Yilmaz  1 , Maro Ohanian  1 , David McCue  1 , Jan Burger  1 , Danielle Hammond  1 , Keyur Patel  2 , Ghayas C Issa  1 , Naveen Pemmaraju  1 , Koji Sasaki  1 , Abhishek Maiti  1 , Hussein A Abbas  1 , Kelly Chien  1 , Koichi Takahashi  1 , Fadi Haddad  1 , Prithviraj Bose  1 , Lucia Masarova  1 , Guillermo Montalban-Bravo  1 , Mahesh Swaminathan  1 , Mark Brandt  1 , Sherry Pierce  1 , Guillermo Garcia-Manero  1 , Farhad Ravandi  1
Affiliations
Clinical Trial

Long-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia

Wei-Ying Jen et al. Cancer. .

Abstract

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL.

Methods: This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6-9 mg/m2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 109/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence.

Results: One hundred forty-six patients (median age, 53.0 years; range, 19.3-83.9 years) were treated, including 106 patients (72.6%) with standard-risk APL and 40 (27.4%) with high-risk APL. GO was administered to 68 standard-risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%-98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow-up of 61.8 months (95% CI, 4.7-128.4 months), the 5-year event-free survival, disease-free survival, and overall survival rates were 92.4% (95% CI, 87.9%-97.1%), 93.6% (95% CI, 89.5%-97.8%), and 93.1% (95% CI, 88.9%-97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno-occlusive disease.

Conclusions: The combination of ATO-ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161).

Keywords: acute promyelocytic leukemia (APL); all‐trans retinoic acid (ATRA); arsenic trioxide (ATO); clinical trial; gemtuzumab ozogamicin (GO).

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Conflict of interest statement

Hagop M. Kantarjian reports personal/consulting fees from AbbVie, Amgen, Astellas Pharma, Curis, Ipsen Biopharmaceuticals Inc., Infinity BiologiX LLC, KAHR, LabCorp, Novartis, Pfizer Brazil, Shenzhen Target Rx, Stemline Therapeutics Inc., and Takeda Oncology; and support for other professional activities from Amphista and Ascentage outside the submitted work. Yesid Alvarado reports support for professional activities from Astellas Pharma and Jazz Pharmaceuticals outside the submitted work. Elias Jabbour reports personal/consulting fees from AbbVie, Adaptive Biotechnologies Corporation, Amgen, Ascentage Pharma, Autolus Ltd., Bristol Myers Squibb Company, Genentech, Novartis, Pfizer Canada Inc., and Takeda Oncology outside the submitted work. Tapan M. Kadia reports grants/contracts from Ascentage Pharma, Bristol Myers Squibb Company, Genentech, and Jazz Pharmaceuticals; and personal/consulting fees from AbbVie, Agios Pharmaceuticals, Genentech, Novartis, and Servier Pharmaceuticals LLC outside the submitted work. Naval G. Daver reports institutional grants/contracts from AbbVie, Amgen, Bristol Myers Squibb Company, Daiichi Sankyo Company. FATE Therapeutics, Genentech USA Inc., Gilead Sciences Inc., Glycomimetics, Hanmi, ImmunoGen Inc., Kite Pharma Inc., Novimmune, Pfizer Inc., Servier Pharmaceuticals LLC, Trillium, and Trovagene; personal/consulting fees from AbbVie, Amgen, Agios Pharmaceuticals Inc., Arog Pharmaceuticals, Astellas Pharma, Bristol Myers Squibb, Celgene, Daiichi Sankyo Company, Genentech, Gilead Sciences Inc., ImmunoGen Inc., Jazz Pharmaceuticals, Kite Pharma Inc., Novartis, Pfizer Inc., Pfizer Canada Inc., Servier Pharmaceuticals LLC, Shattuck Labs, Stemline/Menarini, and Snydax; and support for other professional activities from Karyopharm Therapeutics outside the submitted work. Nicholas J. Short reports grants/contracts from Astellas Pharma, Stemline Therapeutics Inc., Takeda Oncology, and Xencor; and personal/consulting fees from Amgen, Novartis, and Pfizer Canada Inc. outside the submitted work. Nitin Jain reports grants/contracts from AbbVie, ADC Therapeutics, AstraZeneca, Cellectis, FATE Therapeutics, Genentech, Gilead Sciences Inc., and Pharmacyclics LLC; other funding support/gifts from AbbVie, AstraZeneca, Cellectis, and Gilead Sciences Inc.; personal/consulting fees from Adaptive Biotechnologies Corporation, BeiGene USA Inc., Bristol Myers Squibb Company, and Takeda Oncology; and travel support from Pharmacyclics LLC outside the submitted work. Alessandra Ferrajoli reports grants/contracts from AstraZeneca and BeiGene USA Inc.; and support for other professional activities from AbbVie, AstraZeneca, and Janssen Biotech outside the submitted work. Jan Burger reports grants/contracts from AbbVie, AstraZeneca AB, and BeiGene USA Inc.; support for other professional activities from BeiGene USA Inc. and Pharmacyclics LLC; and travel support from Janssen Global Services LLC outside the submitted work. Maro Ohanian reports personal/consulting fees from Bio-Path outside the submitted work. Ghayas C. Issa reports personal/consulting fees from Novartis, Sanofi, and Syndax; and service on a Novartis Data and Safety Monitoring Board outside the submitted work. Naveen Pemmaraju reports grants/contracts from the US Department of Defense; personal/consulting fees from AbbVie, Aptitude Health, Astellas Pharma, Blueprint Medicines Corporation, Bristol Myers Squibb Company, Celgene Corporation, Cimeio Therapeutics AG, ClearView Healthcare Partners, Dava Oncology, Harbourside Press, Immunogen, Incyte Corporation, Novartis, OncoLive, Patient Power, Protagonist Therapeutics, Stemline Therapeutics Inc., and Total CME; and support for other professional activities from the Anaplastic Anemia and MDS International Foundation, Cancer.Net, CareDx, CTI BioPharma, Curio Science, Dan’s House of Hope, EUSA Pharma (US) LLC, Imedex, Karger Publisher, Magdalen Medical Publishing, Medscape, Menarini Group, Neopharm, Payclex, PeerView Institute for Medical Education, PharmaEssentia, Physicians Education Resource, Postgraduate Education Resource, and Targeted Oncology outside the submitted work. Koji Sasaki reports support for professional activities from Amgen, Chugai Pharmaceutical, Daiichi Sankyo Company, Otsuka Pharmaceutical Company Ltd., Novartis, and Pfizer outside the submitted work. Koichi Takahashi reports personal/consulting fees from Otsuka Pharmaceutical and Symbio Pharmaceuticals; and support for other professional activities from Pfizer Inc. outside the submitted work. Prithviraj Bose reports grants/contracts from Ajax Therapeutics, Blueprint Medicines Corporation, Bristol Myers Squibb Company, Cogent BioSciences, CTI BioPharma, Dainippon Sumitomo Pharma, DISC Medicine, Geron Corporation, Incyte Corporation, Ionis Pharmaceuticals, Janssen Biotech Inc., Kartos Therapeutics, Karyopharm Therapeutics Inc., Morphosys, and Telios; and personal/consulting fees from AbbVie, Blueprint Medicines Corporation, Bristol Myers Squibb Company, Cogent BioSciences, CTI BioPharma, Dainippon Sumitomo Pharma, DISC Medicine, Geron Corporation, GlaxoSmithKline, Incyte Corporation, Ionis Pharmaceuticals, Jubilant Therapeutics, Karyopharm Therapeutics Inc., Keros Therapeutics, Morphic Therapeutic, Morphosys, Novartis, Raythera, and PharmaEssentia outside the submitted work. Lucia Masarova reports personal/consulting fees from PharmaEssentia; and support for other professional activities from Cogent Therapeutics LLC, GlaxoSmithKline LLC, and Morphosys outside the submitted work. Farhad Ravandi reports grants/contracts from Bristol Myers Squibb Company and Taiho Pharmaceutical; personal/consulting fees from AbbVie, Amgen, Astellas Pharma, Bristol Myers Squibb Company, Celgene Corporation, Novartis, and Taiho Pharmaceutical; and support for other professional activities from Celgene Corporation outside the submitted work. The remaining authors declared no conflicts of interest.

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References

    1. de Thé H, Chomienne C, Lanotte M, Degos L, Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus. Nature. 1990;347(6293):558–561. - PubMed
    1. Estey E, Garcia-Manero G, Ferrajoli A, et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006;107(9):3469–3473. - PubMed
    1. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia. New England Journal of Medicine. 2013;369(2):111–121. - PubMed
    1. Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial. Blood. 1999;93(12):4131–4143. - PubMed
    1. Sanz MA, Lo Coco F, Martín G, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96(4):1247–1253. - PubMed

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