San Diego, California—Gemtuzumab ozogamicin is safe and tolerable in patients with acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL), but combinations of the drug may be of more value to patients with relapsed or refractory AML and measurable residual disease, according to results from a recent study presented at the 2018 ASH Annual Meeting.

The targeted therapy gemtuzumab ozogamicin initially received FDA approval in 2000 before being voluntarily withdrawn from commercial use for safety concerns, and was re-approved by the FDA in September 2017.

Before being re-approved, adults and children with relapsed or refractory AML or acute promyelocytic leukemia (APL) received treatment with gemtuzumab ozogamicin through an expanded access program at select centers across Seattle, Washington.

Utilizing the data for these patients, Kelda M Gardner, PA-C, Physician Assistant, University of Washington, Seattle, and colleagues, studied the use of gemtuzumab ozogamicin in patients with relapsed or refractory AML or APL in an expanded access setting.

Ms Gardner and colleagues enrolled 44 patients, including 12 children and 32 adults, in the study between 2014 and 2017; the median patient age was 40 years. Of these patients, 40 had AML, 3 had mixed-phenotype acute leukemia, and 1 had APL. A total of 42 patients had relapsed disease, and 2 were primary refractory.

Although patients were initially required to have intermediate or “good” risk cytogenetics for enrollment in the trial, subsequent patients whose blasts were CD33-positive were included regardless of cytogenetics. Eligibility criteria also included Eastern Cooperative Oncology Group performance status ≤3, bilirubin ≤2.0 mg/dL, and alanine transaminase (ALT) and aspartate transaminase (AST) levels ≤5-fold the institutional upper limit of normal.

Gemtuzumab ozogamicin was administered as a single agent to 2 patients, 1 patient with APL was given gemtuzumab ozogamicin plus plus all-trans retinoic acid and azacytidine, and the rest of the participants received gemtuzumab ozogamicin with chemotherapy. Patients were generally given gemtuzumab ozogamicin for a median of 2 cycles; however, the 1 APL patient received 6 cycles of the drug.

In the 60 days following initial receipt of gemtuzumab ozogamicin, patients experienced grade 3 to 4 toxicities, including major infections, such as bacteremia, sepsis, pneumonia, and 1 instance of grade 4 orbital cellulitis (41%); minor infections, mostly fever of unknown origin (66%); increases in ALT and AST levels (9%); back, bone, knee, and tooth pain (9%); rash (9%); hypotension (7%); delirium/encephalopathy (7%); and hypoxia (7%).

There were 2 children who had sinusoidal obstructive syndrome (SOS) in this time frame; both incidences occurred after allogeneic hematopoietic cell transplant. The syndrome resolved in the first patient, who is still alive 2 years later, but an invasive mucormycosis infection in the setting of immunosuppression resulted in the death of the second child.

In addition, in the 60 days after patients started taking gemtuzumab ozogamicin, 6 deaths occurred—1 from cardiogenic shock, 1 from a multi-organ failure postaspiration event, 2 from pneumonia/sepsis, and 2 from disease progression. Of note, there were no mortalities attributed to use of gemtuzumab ozogamicin.

Complete remission (CR) was achieved in 13 (29%) of the 44 enrolled patients (95% confidence interval, 18%-44%); 3 (7%) had measurable residual disease. In 2 patients, measurable residual disease (MRD) was detected via flow cytometry, and in 1 patient, MRD was detected through polymerase chain reaction analysis for inversion 16.

A total of 16 patients had CR with incomplete hematologic recovery (CRi), and 15 were resistant or died before assessment. A median event-free survival of 31 months was achieved by 8 patients who are alive and in CR; however, 36 patients died, with a median survival of 17.2 months.

Ms Gardner and colleagues observed higher rates of response in patients who received gemtuzumab ozogamicin in combination with more intensive therapy versus less intensive therapy (78% CR+Cri vs 44% CR+CRi), and in those with fewer previous treatments (100% CR+CRi with 1 previous regimen vs 48% with ≥2 previous regimens).

Responses were also obtained in patients with intermediate (11 of 19 total intermediate, 58%) or unfavorable (3 of 8 total unfavorable, 37%) risk cytogenetics, although a higher fraction of responses were seen with favorable cytogenetics (15 of 17 total favorable, 88%).

Based on these findings, Ms Gardner and colleagues assert that gemtuzumab ozogamicin demonstrated safety, tolerability, and CR rates comparable to those the patients would have achieved had they received previous intense salvage therapy without gemtuzumab ozogamicin.

“GO [gemtuzumab ozogamicin] combinations are a reasonable option for relapsed/refractory AML, but might be of more value in patients with only measurable residual disease,” they concluded.—Hina Khaliq

Gardner KM, Dorcy KS, O’Leary R, et al. Use of gemtuzumab ozogamicin for the treatment of relapsed or refractory acute myeloid leukemia (AML) or acute promyelocytic leukemia (APL) in an expanded access setting at our cancer consortium. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 2710.