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Acute myeloid leukemia

PTPN11 mutations are associated with poor outcomes across myeloid malignancies

Leukemia volume 35, pages 286–288 (2021)Cite this article

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We read with great interest the letter by Alfayez et al. published in June 2020 on clinical impact of PTPN11 mutations in acute myeloid leukemia (AML). To complement their findings, we report outcomes of a large cohort of PTPN11-mutant (mt) patients across myeloid malignancies. Between 2013 and 2019, all patients with myeloid malignancies and a PTPN11 mutation at Moffitt Cancer Center were identified. A total of 78 PTPN11-mt patients, 56 AML, 14 myelodysplastic syndrome (MDS), 4 MDS/myeloproliferative neoplasm (MPN) and 4 primary myelofibrosis (PMF), were included.

We then compared PTPN11-mt patients to PTPN11-wild type (wt) patients among each disease category. In PTPN11-mt AML patient (n = 56 vs n = 380 in wt AML), similar to Alfayez et al., there was female predominance (54 vs 39% p = 0.04), platelet count was higher (65 vs 45 p = 0.02) and no PTPN11-patients had favorable cytogenetics (0 vs 9% p = 0.02). In our cohort, NPM1 and NRAS were more prevalent in PTPN11-mt AML (p = 0.05 and 0.04). In newly diagnosed patients, there was no difference in overall response rates (ORR) and complete responses (CR) between PTPN11-mt and wt cohorts. The ORR was 73% and CR was 54% with induction chemotherapy (IC) among PTPN11-mt group compared to 70% ORR and 51% CR among patients with PTPN11-wt. For those treated with hypomethylating agents (HMA), ORR was 27% and CR 17% in the PTPN11-mt group compared to 26% ORR and 14% CR in PTPN11-wt. We then looked at transplant outcomes in our AML cohort. 32% of PTPN11-mt AML patient underwent AHSCT vs 26% in the wt group (p = 0.34). PTPN11-mt AML patients who underwent AHSCT had an OS of 24.4 vs 42.7 months in wt patients (p = 0.03) whereas OS in patients that did not undergo AHSCT was 5.6 vs 10.1 months in PTPN11-mt vs wt (p = 0.04). Although similar this difference was not significant in the newly diagnosed cohort alone due to sample size (OS 24.4 vs 42.7 p = 0.12 and 6.8 vs 13.3 p = 0.19). AHSCT significantly improved outcomes for newly diagnosed PTPN11-mt AML patients (OS 24.4 vs 6.8 p = 0.005). Of the 13 patients that underwent AHSCT in PTPN11-mt AML, 92.3% (n = 12) received IC. Given the high frequency in NPM1 mutations in the cohort, we also compared newly diagnosed NPM1-mt/PTPN11-wt to NPM-mt/PTPN11-mt to PTPN11-mt/NPM1-wt AML patients. PTPN11-mt/NPM1-wt AML patients had a significantly worse prognosis (OS 10.3 vs 24.4 and not reached in NPM1-mt/PTPN11-mt and in NPM1-mt/PTPN11-wt p = 0.007). In PTPN11-mt/NPM1-wt, CR rate with IC was 60% and only 11% to HMA (58 and 36% in NPM1-mt cohorts). OS was similar between NPM1-mt/PTPN11-wt and NPM-mt/PTPN11-mt (p = 0.94). Only 26% of PTPN11-mt/NPM-1-wt proceed to AHSCT, however a statistically significant survival benefit was seen in these patients (OS 20.6 vs 6.7 p = 0.04).

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Fig. 1: Distribution of co-occurring somatic gene mutations in PTPN11-mt cohort.

References

  1. Kadia TM, Jain P, Ravandi F, Garcia-Manero G, Andreef M, Takahashi K, et al. TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomes. Cancer. 2016;122:3484–91.

    Article  CAS  Google Scholar 

  2. Stevens BM, Jones CL, Winters A, Dugan J, Abbott D, Savona MR, et al. PTPN11 mutations confer unique metabolic properties and increase resistance to venetoclax and azacitidine in acute myelogenous leukemia. Blood. 2018;132:909.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    David M. Swoboda

  2. Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    Najla Al Ali, Onyee Chan, Eric Padron, Andrew T. Kuykendall, Chetasi Talati, Kendra Sweet, Jeffrey E. Lancet, David A. Sallman & Rami S. Komrokji

  3. Department of Pathology, H. Lee Moffitt Cancer, Tampa, FL, USA

    Jinming Song & Mohammad Hussaini

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  1. David M. Swoboda
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Contributions

DMS wrote manuscript, all authors contributed patients and or collected data and interpreted results. All authors approved final manuscript.

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Correspondence to David M. Swoboda.

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Conflict of interest

DMS, NAA, OC, JS, and MH declare no conflict of interest. EP obtains research funding from Incyte, Kura Oncology and BMS and has received Honorari a from Novartis. ATK is on advisory boards for Blueprint Medicines, Novartis and Prelude and has been part of a speaker’s bureau for BMS. CT is on advisory boards for Abbvie, Celgene, Pfizer, BMS and Novartis and has been part of a speaker’s bureau for Astellas, BMS and Jazz. KS is on advisory committees for Takeda, BMS, Novartis, Agios. She has received research funding from Incyte and has received Honoraria from Stemline and Astellas. JEL has done consulting for AbbVie, Agios, Astella, Daiichi Sankyo, ElevateBio, Jazz and received Honoria from Agios. DAS has received research funding from Celgene and Jazz and done consulting for Celyad, Incyte, Novartis, Agios, BMS, Intellia, Kite and Syndax. RSK has been part of a speaker’s bureau for Jazz, BMS and Agios and received honoraria from Abbvie, Incyte, Acceleron, Novartis and Geron.

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Swoboda, D.M., Ali, N.A., Chan, O. et al. PTPN11 mutations are associated with poor outcomes across myeloid malignancies. Leukemia 35, 286–288 (2021). https://doi.org/10.1038/s41375-020-01083-3

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