The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Combination gemtuzumab ozogamicin (GO) and cytarabine is no more effective than standard chemotherapy for older adults with previously untreated, standard-risk acute myeloid leukemia (AML), a phase 2/3 trial suggests. 

In fact, GO plus cytarabine was associated with worse event-free survival (EFS) in women. 

These findings were presented at the 2021 American Society of Hematology (ASH) Annual Meeting by Juliette Lambert, MD, PhD, of Versailles Hospital in France. 


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The ALFA-0701-Mylofrance 4 study (ClinicalTrials.gov Identifier: NCT02473146) included 214 patients with treatment-naïve AML. Patients were randomly assigned 2:1 to receive GO-cytarabine (n=143) or standard anthracycline-cytarabine (n=71). 

The median age was 69 years (range, 62-79 years) in the standard arm and 70.5 years (range, 61-80 years) in the GO arm. A majority of patients (94% in the standard arm and 93% in the GO arm) had intermediate-risk cytogenetics.

Induction therapy in the standard arm consisted of idarubicin (12 mg/m2 on days 1-3) plus cytarabine (200 mg/m2 on days 1-7). In the GO arm, patients received GO (3 mg/m2 on days 1 and 4) plus cytarabine (200 mg/m2 on days 1-7). 

First consolidation or salvage therapy consisted of cytarabine alone (1.5 mg/m2 on days 1, 3, and 5) in the standard arm. In the GO arm, patients received the same schedule of cytarabine plus GO (3 mg/m2 on day 1). Patients who achieved a complete response (CR) in either arm went on to receive additional cytarabine at the same schedule.

Results

The composite response rate (CR with or without incomplete hematologic/platelet count recovery) was 90% in the standard arm and 82% in the GO arm (P =.73). The CR rate was 72% and 68%, respectively.

The median EFS was 15.2 months in the standard arm and 12.4 months in the GO arm (hazard ratio [HR], 1.37; 95% CI, 0.98-1.93; P =.067). 

The researchers also analyzed EFS among patients who did not proceed to allogeneic hematopoietic stem cell transplant (allo-HSCT), as more patients in the standard treatment arm received an allo-HSCT (30% vs 12%). 

Removing the allo-HSCT recipients did not affect the outcome. The median EFS was 15.1 months in the standard arm and 12.1 months in the GO arm (HR, 1.27; 95% CI, 0.88-1.83; P =.19).

In a subgroup analysis for EFS, the researchers found that women had significantly worse EFS on GO (HR, 2.62; 95% CI, 1.54-4.46; P =.0017). The team was surprised by this finding and has no explanation for it yet, according to Dr Lambert. 

“We compared the female patients between arms, and we didn’t find any explanation,” she said. “This is the same population, same biological or clinical characteristics, and we didn’t find any more relapses or toxicities [among women on GO]. We tried to find a way to understand why GO seems to be detrimental for women, but it seems we have no explanation.” 

At 2 years, the cumulative incidence of relapse was 48% in the standard arm and 61% in the GO arm (HR, 1.39; 95% CI, 0.93-2.06; P =.11).

The median overall survival was 36.5 months in the standard arm and 25.5 months in the GO arm (HR, 1.27; 95% CI, 0.86-1.87; P =.23).

Grade 3-5 AEs were seen in 78% of the standard arm and 77% of the GO arm (P =.73). The most common AEs (in the standard and GO arms, respectively) were infection (30% vs 21%), bleeding (7% vs 29%), and cardiac disorders (15% vs 21%). 

Patients in the GO arm had significantly more serious AEs than those in the standard arm — 48% and 35%, respectively (P =.041). 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.

Reference

Lambert J, Lambert J, Lemasle E, et al. Replacing the anthracycline by gemtuzumab ozogamicin in older patients with de novo standard-risk acute myeloid leukemia treated intensively – Results of the randomized ALFA1401-Mylofrance 4 Study. Presented at ASH 2021; December 11-14, 2021. Abstract 31.