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Clinical Trial
. 2024 May 23;1(3):100017.
doi: 10.1016/j.bneo.2024.100017. eCollection 2024 Sep.

Real-world outcomes of newly diagnosed AML treated with venetoclax and azacitidine or low-dose cytarabine in the UK NHS

Jad Othman  1   2   3 , Ho Pui Jeff Lam  4 , Sarah Leong  4 , Faisal Basheer  5 , Islam Abdallah  6 , Kathryn Fleming  7 , Priyanka Mehta  7 , Heba Yassin  8 , John Laurie  8 , Michael Austin  9 , Paolo Gallipoli  9 , Tom Taylor  10 , Mike Dennis  11 , Johnathon Elliot  11 , Georgina Clarke  12 , Raymond Dang  12 , Jennifer Vidler  13 , Pramila Krishnamurthy  13 , Anne-Louise Latif  14 , Pallavi Kalkur  15 , Maryam Shahidianakbar  16 , Victoria Campbell  17 , Deepak Mannari  18 , Emily Sutherland  19 , Thishakya Wickramaratne  20 , Angela Collins  21 , Rui Zhao  22 , Herng Mak  23 , Edward Belsham  24 , Shabnam Banerjee  25 , Jamila Bashir  26 , Srinivas Pillai  27 , Richard Whitmill  28 , Sofia Galli  29 , Mariam Amer  30 , Vidhya Murthy  31 , Duncan Murray  32 , Farooq Wandroo  33 , Francesca Hogan  34 , Francesca Crolla  35 , Nicole Fowler  36 , Anjum Khan  6 , Jenny O'Nions  4 , Richard Dillon  1   2
Affiliations
Clinical Trial

Real-world outcomes of newly diagnosed AML treated with venetoclax and azacitidine or low-dose cytarabine in the UK NHS

Jad Othman et al. Blood Neoplasia. .

Abstract

Venetoclax with azacitidine is the standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy; however, uncertainties remain regarding the treatment schedule, accurate prognostication, and outcomes for patients treated outside clinical trials. The option of venetoclax with low-dose cytarabine (LDAC) is also available; however, it is not clear for which patients it may be a useful alternative. Here, we report a large real-world cohort of 654 patients treated in 53 UK hospitals with either venetoclax and azacitidine (n = 587) or LDAC (n = 67). The median age was 73 years, and 59% had de novo AML. Most patients received 100 mg of venetoclax with an azole antifungal. In cycle 1, patients spent a median of 14 days in the hospital, and 85% required red cell transfusion, 59% platelet transfusion, and 63% required IV antibiotics. Supportive care requirements significantly reduced after the first cycle. Patients receiving venetoclax-azacitidine had a complete remission (CR)/CR with incomplete hematological recovery rate of 67%, day 30 and day 60 mortality of 5% and 8%, respectively, and median overall survival of 13.6 months. Mutations in NPM1, RUNX1, STAG2, and IDH2 were associated with improved survival, whereas age, secondary and therapy-related AML, +8, MECOM rearrangements, complex karyotype, ASXL1, and KIT mutations were associated with poorer survival. Prognostic systems derived specifically for patients treated with venetoclax-azacitidine performed better than the European LeukemiaNet and Medical Research Council classifications; however, improved risk classifications are still required. In the 149 patients with NPM1 mutated AML, outcomes were similar for those treated with venetoclax-azacitidine and venetoclax-LDAC.

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Conflict of interest statement

Conflict-of-interest disclosure: J. Othman declares honoraria from Astellas and Jazz Pharmaceuticals; and speaker’s fees and advisory board fees from Pfizer, Jazz Pharmaceuticals, Astellas, and AbbVie. P.G. declares honoraria from Astellas. F.H. declares meeting sponsorship and honoraria from AbbVie. R. Dang declares meeting sponsorship from Jazz; and honoraria from AbbVie. J.V. declares meeting support from BeiGene, Janssen, and Jazz; and honoraria from AbbVie and AstraZeneca. P. Krishnamurthy declares honoraria from Jazz, Astellas, and Gilead; speaker’s bureau with Astellas; and consultancy for Jazz and Gilead. A.-L.L. declares honoraria from Astella, AbbVie, Amgen, Kite, Novartis, Jazz, and Daiichi Sankyo; and speaker’s bureau with Kite, Takeda, and Astellas. V.M. declares consultancy and honoraria from AbbVie. N.F. declares investigator meetings with Novartis and MEI Pharma. A.K. declares meeting sponsorship from Jazz, Medac, and Servier; speaker’s bureau with AbbVie, Astellas, Jazz and Servier; and consultancy/advisory board for TC BioPharm, Novartis, Synairgen, and Takeda. J. O'Nions declares honoraria from AbbVie, Astellas, Janssen, Jazz and Servier. R. Dillon declares research funding from AbbVie and Amgen; and consultancy with Astellas, Pfizer, Novartis, Jazz, BeiGene, Shattuck, and AvenCell. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Count recovery and supportive care requirements in cycles 1-4. (A) Days between consecutive cycles. (B) Proportion of patients requiring supportive care measures in cycles 1 to 4. (C) Time to neutrophil and platelet recovery for patients who achieved CR/CRi.
Figure 2.
Figure 2.
Characteristics associated with achievement of remission with venetoclax and azacitidine. (A) Univariable odds ratios for not achieving CR/CRi (factors with odds ratio <1 are associated with achievement of CR/CRi). (B) Rate of CR/CRi in clinical and genomic subgroups. (C) Cumulative incidence of relapse for patients who achieved CR/CRi.
Figure 3.
Figure 3.
Characteristics associated with OS with venetoclax and azacitidine. (A) Univariable hazard ratios for OS. (B) Multivariable Cox regression for OS. (C) Kaplan-Meier plot of OS. ∗Cytogenetic change in absence of complex karyotype.
Figure 4.
Figure 4.
Rates of CR/CRi, 12-month OS, and Kaplan-Meier survival plots for established and proposed AML prognostication systems for patients treated with venetoclax and azacitidine. (A) MRC 2010 cytogenetic risk. (B) ELN 2022 risk. (C) 4-gene prognostic signature proposed by Döhner et al, from VIALE-A study. (D) Molecular predictors of response and treatment failure, DiNardo et al. (E) Mayo predictors of treatment response, Gangat et al.
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