Safety of gemtuzumab ozogamicin as monotherapy or combination therapy in an expanded-access protocol for patients with relapsed or refractory acute myeloid leukemia

Abstract

Gemtuzumab ozogamicin (GO) remained available to US clinicians through an open-label expanded-access protocol (NCT02312037) until GO was reapproved. Patients were aged ≥3 months with relapsed/refractory (R/R) acute myeloid leukemia (AML), high-risk myelodysplastic syndrome, or acute promyelocytic leukemia (APL), and had exhausted other treatment options. Three hundred and thirty one patients received GO as monotherapy for R/R AML (n = 139), combination therapy for R/R AML (n = 183), or treatment for R/R APL (n = 9). Corresponding treatment discontinuations occurred in 68, 39, and 33% of patients. All-causality grade 5 AEs occurred in 52, 22, and 22% of patients in the monotherapy, combination, and APL groups, respectively. Corresponding grades 3 and 4 treatment-related AEs were reported in 60, 55 and 78% of patients. Hepatotoxicity occurred in five patients: veno-occlusive disease (n = 4) and drug-induced liver injury (n = 1). GO was generally well tolerated in patients with R/R AML or APL. Most frequent treatment-related grade ≥3 AEs were hematologic AEs.

Clinicaltrials.gov identifier: NCT02312037

Keywords:

• Acute myeloid leukemia
• acute promyelocytic leukemia
• expanded access
• gemtuzumab ozogamicin
• myelodysplastic syndrome
• safety

Acknowledgments

The study was sponsored by Pfizer. Medical writing support was provided by Anne Marie McGonigal, PhD, of Engage Scientific Solutions and was funded by Pfizer.

Author contributions

All authors were involved in the trial conception/design, or the acquisition, analysis or interpretation of data. All authors contributed to the drafting of the manuscript and approved the final version.

Disclosure statement

• Eunice S. Wang: consultancy for Pfizer, AbbVie, Amgen, Agios, AROG, Dava Oncology, ImmunoGen, Jazz Pharmaceuticals, Daiichi Sankyo, Celyad; Speakers Bureaux for Novartis, Astellas and Jazz Pharmaceuticals.

• Richard Aplenc: no conflicts to disclose.

• Deborah Chirnomas: was an employee of Pfizer at the time of the study.

• Michael Dugan: consultancy for AbbVie; Speakers Bureau for Celgene; research funding from Pfizer.

• Salman Fazal: Advisory Committee for Incyte, Bristol-Myers Squibb, Jazz Pharmaceuticals, Gilead, Pfizer, Novartis, GlaxoSmith Kline, Amgen; Speakers Bureaux for Incyte, Bristol-Myers Squibb, Jazz Pharmaceuticals, Gilead, Pfizer, Novartis, Stemline Therapeutics, Janssen Pharmaceuticals, Takeda, GlaxoSmith Kline, Karyopharm, Amgen.

• Swaminathan Iyer: no conflicts to disclose.

• Tara L. Lin: honoraria from Jazz Pharmaceuticals and Advisory Committee for Pfizer.

• Sucha Nand: Advisory Committee for Pfizer.

• Kristen J. Pierce: employee of Pfizer.

• Paul J. Shami: employee of JSK Therapeutics; equity ownership in JSK Therapeutics and Lone Star Thiotherapies; consultancy for Pfizer, Jazz Pharmaceuticals, AbbVie and Agios; research support from Pfizer, Amgen and Aptevo; Board of Directors/Advisory Committee for JSK Therapeutics and Lone Star Thiotherapies.

• Jennifer J. Vermette: employee of Pfizer.

• Camille N. Abboud: consultancy for Pfizer, Agios, Cardinal Health and Gerson Lehrman Group; honoraria from Jazz Pharmaceuticals, Agios and Cardinal Health; Speakers Bureau for Jazz Pharmaceuticals; Dava Oncology Expert.

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