Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Mar;40(3):227-235.
doi: 10.1007/s40261-019-00881-7.

Practical Considerations for Treatment of Relapsed/Refractory FLT3-ITD Acute Myeloid Leukaemia with Quizartinib: Illustrative Case Reports

Affiliations
Review

Practical Considerations for Treatment of Relapsed/Refractory FLT3-ITD Acute Myeloid Leukaemia with Quizartinib: Illustrative Case Reports

David Martínez-Cuadrón et al. Clin Drug Investig. 2020 Mar.

Abstract

Quizartinib is a tyrosine kinase inhibitor selectively targeting the FMS-like tyrosine kinase 3 (FLT3) receptor that has been developed for the treatment of acute myeloid leukaemia (AML). The Phase 3 QuANTUM-R study investigated the efficacy of quizartinib monotherapy in patients with relapsed/refractory FLT3-ITD mutation-positive AML. The clinical course of four QuANTUM-R participants exemplifies issues specific to quizartinib treatment and is described here. Patient 1 was FLT3-ITD mutation-negative at AML diagnosis, but became FLT3-ITD mutation-positive during treatment that included several lines of chemotherapy and was therefore a suitable candidate for quizartinib. Because of the clonal shifts of AML during treatment, retesting genetic alterations at each relapse or resistance may help to identify candidates for targeted treatment options. Patient 2 developed QTc prolongation during quizartinib treatment, but the QTc interval normalised after dose reduction, allowing the patient to continue treatment and eventually resume the recommended dose. Patient 3 responded to quizartinib and was scheduled for haematopoietic stem cell transplant (HSCT), but developed febrile neutropenia and invasive aspergillosis during conditioning and subsequently died (to avoid drug-drug interactions, no azole antifungal was administered concomitantly). Care is required when selecting concomitant medications, and if there is potential for interactions (e.g. if prophylactic azole antifungals are required) the quizartinib dose should be reduced to minimise the risk of QTc prolongation. Patient 4 was able to undergo HSCT after responding to quizartinib and experienced a durable response after HSCT while on quizartinib maintenance therapy. Together, these cases illustrate the main issues to be addressed when managing patients under quizartinib, allowing for adequate scheduling and tolerability, bridging to HSCT, and durable remission on maintenance therapy in some patients.

PubMed Disclaimer

Conflict of interest statement

David Martínez-Cuadrón has acted in an advisory role for JazzPharma, Novartis, Pfizer, Teva and Daiichi Sankyo; has served on the Speakers’ Bureau of Pfizer, Janssen, Amgen and Gilead; and has received travel grants from JazzPharma, Novartis, Pfizer and Amgen. Pau Montesinos has provided consultations or acted in an advisory role for JazzPharma, Novartis, AbbVie, Celgene, Shire, Takeda, Daiichi Sankyo, Pfizer, Tolero and Agios; has served on the Speakers’ Bureau of Otsuka, Novartis, AbbVie, Celgene, Incyte, Daiichi Sankyo and Pfizer; has received research funding from Novartis, Janssen, Celgene, Daiichi Sankyo, Pfizer and Teva; and has received travel grants from Teva, Novartis, Celgene, Daiichi Sankyo and Amgen. Rebeca Rodríguez-Veiga has served on the Speakers’ Bureau of Teva, Pfizer, Janssen and Novartis; and has received travel grants from Sanofi and Daiichi Sankyo. All other co-authors: nothing to disclose.

Figures

Fig. 1
Fig. 1
Axial CT scan at the C1 level showing submaxillary swelling and lymphadenopathy on the left side
Fig. 2
Fig. 2
Coronal (a) and axial (b) CT scans of the abdomen showing extramedullary disease with ureteral involvement after cycle 9 of quizartinib
Fig. 3
Fig. 3
ECG from a patient (a) at screening, showing a normal QTcF interval (385 ms), and (b) during quizartinib 60 mg, when QTcF was prolonged to 488 ms, prompting a dose reduction

Similar articles

Cited by

References

    1. Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136–1152. doi: 10.1056/NEJMra1406184. - DOI - PubMed
    1. Grove CS, Vassiliou GS. Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer? Dis Model Mech. 2014;7(8):941–951. doi: 10.1242/dmm.015974. - DOI - PMC - PubMed
    1. Ley TJ, Miller C, Ding L, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–2074. doi: 10.1056/NEJMoa1301689. - DOI - PMC - PubMed
    1. Mrozek K, Marcucci G, Paschka P, et al. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood. 2007;109(2):431–448. doi: 10.1182/blood-2006-06-001149. - DOI - PMC - PubMed
    1. Boissel N, Cayuela JM, Preudhomme C, et al. Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy. Leukemia. 2002;16(9):1699–1704. doi: 10.1038/sj.leu.2402622. - DOI - PubMed

LinkOut - more resources