Gemtuzumab ozogamicin plus 7 + 3 induction therapy in patients with intermediate-risk ND AML

Gemtuzumab ozogamicin (GO) has shown survival benefits when added to intensive induction regimens in patients with newly diagnosed acute myeloid leukemia and favorable cytogenetics. The smaller survival benefit observed in patients with intermediate-risk cytogenetics has led to the omittance of GO from intensive regimens for this patient group.

Recently, Awada, et al.¹ published a retrospective analysis of real-world outcomes in Blood Cancer Journal investigating whether the addition of GO to intensive 7 + 3 induction therapy is beneficial in intermediate-risk patients. Here we summarize the key results.

Study design¹

• In this retrospective analysis of real-world outcomes, data was collected between 2015 and 2023.
• Patients received either GO plus 7 + 3 or 7 + 3 alone.
• Study endpoints were response rates as defined by the European LeukemiaNet 2022 criteria, measurable residual disease, relapse rate, rate of successful bridging to allogeneic hematopoietic stem cell transplantation, leukemia-free survival (LFS), and overall survival (OS).

Key findings¹

• N = 113
  • 33 patients in the GO plus 7 + 3 cohort
  • 80 patients in the 7 + 3 alone cohort
• The median follow-up was 26.8 months.
• The percentage of patients achieving a complete response/complete response with incomplete count recovery, negative measurable residual disease, and bridging to allogeneic hematopoietic stem cell transplantation were higher in those treated with GO plus 7 + 3 vs 7 + 3 alone (Figure 1).

Allo-HSCT, allogenic-hematopoietic stem cell transplantation; CR, complete response; CRi, complete response with incomplete count recovery; GO, gemtuzumab ozogamicin; MRD, measurable residual disease.
*Adapted from Awada, et al.^1
†GO plus 7 + 3 (n = 18), 7 + 3 alone (n = 14).
^‡GO plus 7 + 3 (n = 16), 7 + 3 alone (n = 22).

• There was a trend towards superior OS and LFS in patients treated with GO plus 7 + 3 vs 7 + 3 alone (median not reached vs 39 months, and median not reached vs 31.5 months, respectively).
• Platelet count recovery was slower in patients treated with GO plus 7 + 3 vs 7 + 3 alone (31 days vs 25 days, p = 0.001).
• FLT3, IDH1/2, KRAS/NRAS, and RUNX1 mutations were more common in patients who responded to GO plus 7 + 3 than those who did not, whereas mutations in ASXL1, DNMT3A, TET2, and TP53 occurred more frequently in patients not-responding to GO plus 7 + 3.
  • In comparison, ASXL1 and BCOR/BCORL1 mutations were common in responders to 7 + 3 alone, while NPM1 mutations were enriched in 7 + 3 non-responders.

Key learnings
The addition of GO to 7 + 3 induction therapy resulted in improved response rates and relapse risk in patients with newly diagnosed acute myeloid leukemia and intermediate-risk cytogenetics. Investigations in larger patient populations, and over a longer follow-up period, are needed to further clarify the impact of GO on OS and LFS.