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A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia

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Abstract

Purpose

The purpose of this study was to identify the incidence, sites and main pathogens, and risk factors for infectious complications occurring in patients with adult acute myeloid leukemia (AML) during the first course of venetoclax combined with decitabine or azacitidine.

Methods

A retrospective cohort analysis was performed of 81 patients with AML older than 14 years who received the first cycle of venetoclax combined with a hypomethylating agent (HMA) between March 2018 and March 2021 at our institution. Infectious complications, if any, were documented.

Results

Among a total of 81 cases of AML, 59 (72.8%) patients occurred infections, including fever without an identifiable source (28.8%), clinically documented infections (40.7%), and microbiologically documented infections (30.5%). The most commonly isolated organism in culture was Candida albicans, followed by Klebsiella pneumonia, and Pseudomonas aeruginosa. The 4-week and 8-week mortality rates were 3.7% and 7.4%, respectively. In multivariate analysis, a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline were significant independent risk factors for infectious complications.

Conclusion

Compared with conventional chemotherapy, the incidence of infectious complications of venetoclax combined with decitabine or azacitidine significantly decreased. Pretreatment high leukemia burden and fever were independent risk factors for infections.

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Data availability

The datasets used during the current study are available from the corresponding author on reasonable request.

References

  1. Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk KM, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G (2009) High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 361(13):1235–1248. https://doi.org/10.1056/NEJMoa0901409

    Article  PubMed  Google Scholar 

  2. Walter RB, Othus M, Borthakur G, Ravandi F, Cortes JE, Pierce SA, Appelbaum FR, Kantarjian HA, Estey EH (2011) Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29(33):4417–4423. https://doi.org/10.1200/jco.2011.35.7525

    Article  Google Scholar 

  3. Atallah E, Cortes J, O’Brien S, Pierce S, Rios MB, Estey E, Markman M, Keating M, Freireich EJ, Kantarjian H (2007) Establishment of baseline toxicity expectations with standard frontline chemotherapy in acute myelogenous leukemia. Blood 110(10):3547–3551. https://doi.org/10.1182/blood-2007-06-095844

    Article  CAS  PubMed  Google Scholar 

  4. Cannas G, Pautas C, Raffoux E, Quesnel B, de Botton S, de Revel T, Reman O, Gardin C, Elhamri M, Boissel N, Fenaux P, Michallet M, Castaigne S, Dombret H, Thomas X (2012) Infectious complications in adult acute myeloid leukemia: analysis of the Acute Leukemia French Association-9802 prospective multicenter clinical trial. Leuk Lymphoma 53(6):1068–1076. https://doi.org/10.3109/10428194.2011.636812

    Article  CAS  PubMed  Google Scholar 

  5. Kato H, Fujita H, Akiyama N, Kimura SI, Hiramoto N, Hosono N, Takahashi T, Shigeno K, Minamiguchi H, Miyatake J, Handa H, Kanda Y, Yoshida M, Miyawaki S, Ohtake S, Naoe T, Kiyoi H, Matsumura I, Miyazaki Y (2018) Infectious complications in adults undergoing intensive chemotherapy for acute myeloid leukemia in 2001–2005 using the Japan Adult Leukemia Study Group AML201 protocols. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 26(12):4187–4198. https://doi.org/10.1007/s00520-018-4292-0

    Article  Google Scholar 

  6. Konopleva M, Letai A (2018) BCL-2 inhibition in AML: an unexpected bonus? Blood 132(10):1007–1012. https://doi.org/10.1182/blood-2018-03-828269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Guerra VA, DiNardo C, Konopleva M (2019) Venetoclax-based therapies for acute myeloid leukemia. Best Pract Res Clin Haematol 32(2):145–153. https://doi.org/10.1016/j.beha.2019.05.008

    Article  PubMed  PubMed Central  Google Scholar 

  8. DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A (2019) Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood 133(1):7–17. https://doi.org/10.1182/blood-2018-08-868752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW (2020) Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med 383(7):617–629. https://doi.org/10.1056/NEJMoa2012971

    Article  CAS  PubMed  Google Scholar 

  10. Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ (2019) Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 37(15):1277–1284. https://doi.org/10.1200/jco.18.01600

    Article  CAS  Google Scholar 

  11. Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P (2020) Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood 135(24):2137–2145. https://doi.org/10.1182/blood.2020004856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD (2003) Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 21(24):4642–4649. https://doi.org/10.1200/jco.2003.04.036

    Article  Google Scholar 

  13. Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, Karthaus M, Link H, Mahlberg R, Neumann S, Ostermann H, Penack O, Ruhnke M, Sandherr M, Schiel X, Vehreschild JJ, Weissinger F, Maschmeyer G (2017) Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol 96(11):1775–1792. https://doi.org/10.1007/s00277-017-3098-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chinese Society of Hematology, Chinese Medical Association, Chinese Medical Doctor Association, Hematology Branch (2020) Chinese guidelines for the clinical application of antibacterial drugs for agranulocytosis with fever (2020). Zhonghua xue ye xue za zhi 41(12):969-78. https://doi.org/10.3760/cma.j.issn.0253-2727.2020.12.001

  15. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 52(4):427–431. https://doi.org/10.1093/cid/ciq147

    Article  Google Scholar 

  16. Pollyea DA, Amaya M, Strati P, Konopleva MY (2019) Venetoclax for AML: changing the treatment paradigm. Blood Adv 3(24):4326–4335. https://doi.org/10.1182/bloodadvances.2019000937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA (2018) Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol 19(2):216–228. https://doi.org/10.1016/s1470-2045(18)30010-x

    Article  CAS  PubMed  Google Scholar 

  18. Pleyer L, Stauder R, Burgstaller S, Schreder M, Tinchon C, Pfeilstocker M, Steinkirchner S, Melchardt T, Mitrovic M, Girschikofsky M, Lang A, Krippl P, Sliwa T, Egle A, Linkesch W, Voskova D, Angermann H, Greil R (2013) Azacitidine in patients with WHO-defined AML - results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group. J Hematol Oncol 6:32. https://doi.org/10.1186/1756-8722-6-32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cashen AF, Schiller GJ, O’Donnell MR, DiPersio JF (2010) Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 28(4):556–561. https://doi.org/10.1200/jco.2009.23.9178

    Article  CAS  Google Scholar 

  20. Chua CC, Roberts AW, Reynolds J, Fong CY, Ting SB, Salmon JM, MacRaild S, Ivey A, Tiong IS, Fleming S, Brown FC, Loo S, Majewski IJ, Bohlander SK, Wei AH (2020) Chemotherapy and venetoclax in elderly acute myeloid leukemia trial (CAVEAT): a phase Ib dose-escalation study of venetoclax combined with modified intensive chemotherapy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 38(30):3506–3517. https://doi.org/10.1200/jco.20.00572

    Article  CAS  Google Scholar 

  21. DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY (2020) 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. The Lancet Haematology 7(10):e724–e736. https://doi.org/10.1016/s2352-3026(20)30210-6

    Article  PubMed  PubMed Central  Google Scholar 

  22. Garcia JB, Lei X, Wierda W, Cortes JE, Dickey BF, Evans SE, Ost DE (2013) Pneumonia during remission induction chemotherapy in patients with acute leukemia. Ann Am Thorac Soc 10(5):432–440. https://doi.org/10.1513/AnnalsATS.201304-097OC

    Article  PubMed  PubMed Central  Google Scholar 

  23. Pandian J, Raghavan V, Manuprasad A, Shenoy PK, Nair CK (2020) Infection at diagnosis-a unique challenge in acute myeloid leukemia treatment in developing world. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 28(11):5449–5454. https://doi.org/10.1007/s00520-020-05379-z

    Article  Google Scholar 

  24. Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA, Nastoupil LJ, Rajotte M, Rolston KV, Strasfeld L, Flowers CR (2018) antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 36(30):3043–3054. https://doi.org/10.1200/jco.18.00374

    Article  Google Scholar 

  25. Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, Allione B, D’Antonio D, Buelli M, Nosari AM, Cilloni D, Zuffa E, Cantaffa R, Specchia G, Amadori S, Fabbiano F, Deliliers GL, Lauria F, Foà R, Del Favero A (2005) Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med 353(10):977–987. https://doi.org/10.1056/NEJMoa044097

    Article  CAS  PubMed  Google Scholar 

  26. Mikulska M, Averbuch D, Tissot F, Cordonnier C, Akova M, Calandra T, Ceppi M, Bruzzi P, Viscoli C (2018) Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect 76(1):20–37. https://doi.org/10.1016/j.jinf.2017.10.009

    Article  PubMed  Google Scholar 

  27. Gafter-Gvili A, Fraser A, Paul M, Leibovici L (2005) Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med 142(12 Pt 1):979–995. https://doi.org/10.7326/0003-4819-142-12_part_1-200506210-00008

    Article  PubMed  Google Scholar 

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Funding

The research was supported by a grant from Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (No.2017KY059).

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Author notes

  1. Li-xia Zhu and Rong-rong Chen contributed equally.

Authors and Affiliations

  1. Department of Hematology, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, Zhejiang, China

    Li-xia Zhu, Rong-rong Chen, Lu-lu Wang, Jia-nai Sun, De Zhou, Li Li, Jie-jing qian, Yi Zhang, Hong-yan Tong, Wen-juan Yu, Hai-tao Meng, Wen-yuan Mai, Wan-zhuo Xie, Jie Jin, Xiu-jin Ye & Hong-hu Zhu

  2. Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, China

    Li-xia Zhu, Jia-nai Sun, De Zhou, Li Li, Jie-jing qian, Yi Zhang, Hong-yan Tong, Wen-juan Yu, Hai-tao Meng, Wen-yuan Mai, Wan-zhuo Xie, Jie Jin, Xiu-jin Ye & Hong-hu Zhu

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  1. Li-xia Zhu
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Contributions

All authors contributed to the study conception and design. Lixia Zhu and Rongrong Chen conducted the hospital chart review, interpreted data, drafted the work, and wrote the final report. Lulu Wang, Jianai Sun, De Zhou, Li Li, Jiejing Qian, and Yi Zhang conducted the hospital chart review. Hongyan Tong, Wenjuan Yu, Haitao Men, Wenyuan Mai, Wanzhuo Xie, and Jie Jin contributed the data interpretation. Honghu Zhu and Xiujin Ye designed the research study and participated in critical revision of manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiu-jin Ye or Hong-hu Zhu.

Ethics declarations

Ethics approval

This study was approved by the clinical research ethics committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (Reference Number 2021-IIT-558).

Consent to participate

The informed consent was waived because this study was a retrospective study with review of related data through the electronic medical record.

Consent for publication

The informed consent was waived because this study was a retrospective study with review of related data through the electronic medical record.

Competing interests

The authors declare no competing interests.

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Li-xia Zhu and Rong-rong Chen share first authorship.

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Zhu, Lx., Chen, Rr., Wang, Ll. et al. A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia. Support Care Cancer 30, 7031–7038 (2022). https://doi.org/10.1007/s00520-022-07126-y

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