Selection and management of older patients with acute myeloid leukemia treated with glasdegib plus low-dose cytarabine: expert panel review

Abstract

Glasdegib, in combination with low-dose cytarabine (LDAC), is the first smoothened inhibitor approved for treatment of acute myeloid leukemia. Glasdegib plus LDAC is indicated for patients in whom therapy options are limited, e.g. older patients and those ineligible for intensive chemotherapy due to preexisting comorbidities. This review summarizes the recommendations of a panel of hemato-oncologists regarding the selection of patients best suited for treatment with glasdegib plus LDAC and the management during therapy with this combination. The panel considered the impact of concomitant medications and comorbidities during treatment with glasdegib plus LDAC, and discussed common adverse events (AEs) associated with glasdegib plus LDAC. Management strategies for AEs discussed by the panel included dose modifications, supportive care therapies, and prophylactic treatments. Finally, the panel highlighted the importance of patient communication and education regarding the possible AEs that may occur during treatment.

Keywords:

• Acute myeloid leukemia
• adverse events
• comorbidities
• glasdegib
• low-dose cytarabine
• older patients

Acknowledgements

The authors would like to thank B. Douglas Smith for his contributions to the advisory board discussions. Medical writing support, under the direction of the authors, was provided by Anne Marie McGonigal, PhD, of Engage Scientific Solutions, and funded by Pfizer.

Disclosure statement

Jorge E. Cortes: consultancy from Pfizer, Novartis, Takeda, Jazz, Biopath Holdings, BiolineRx; grants from Pfizer, Novartis, Takeda, Jazz, BMS, Forma Therapeutics, Amphivena, Merus; other support, e.g. travel to meetings, from Pfizer.

Anna Candoni: board membership, consultancy and speaker's bureau from Gilead, Novartis, Pfizer, Celgene, Janssen, Incyte, MSD.

Richard E. Clark: consultancy from Pfizer, Jazz, Abbvie, Novartis, BMS; grants from Novartis, BMS; speaker's bureau from Pfizer; other support, e.g. travel to meetings, from Pfizer.

Michael Heuser: consultancy from Pfizer, Bayer Pharma AG, Novartis, Prime Oncology, Abbvie, Daiichi Sankyo; grants from Pfizer, Astellas, Bayer Pharma AG, Daiichi Sankyo, BergenBio, Karyopharm, Novartis, Roche.

Brian Leber: board membership, consultancy, expert testimony, speaker's bureau, other support, e.g. travel to meetings, from Pfizer.

Pau Montesinos: consultancy, grants, speaker's bureau from Pfizer.

Paresh Vyas: consultancy, other support, e.g. travel to meetings, from Pfizer; grants from BMS/Celgene, Novartis, Merck; speaker's bureau from AbbVie, BMS/Celgene, Novartis, Pfizer, Jazz, Astellas, Daiichie Sankyo; royalties to institution from BD.

Amer M. Zeidan: consultancy from Celgene/BMS, Abbvie, Pfizer, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, Novartis, Otsuka, Jazz, Agios, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Ionis, Epizyme; grants from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, Novartis, Aprea, ADC Therapeutics.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The authors were not paid for the development of this manuscript. The authors had final authority, including choice of journal, on all aspects of the manuscript content and development. Pfizer funded the medical advisory board meeting for the discussion of treatment decision-making in AML, and provided a formal review of the publication, including for medical accuracy. The experts were compensated for expenses for their attendance at the medical advisory board meeting, from which the authors decided to proceed with the preparation of the manuscript; however, they were not compensated for manuscript preparation. The BRIGHT AML 1003 trial reviewed in this article is a clinical study sponsored by Pfizer.