A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia

Abstract

Key Points• The addition of gemtuzumab ozogamicin to induction or maintenance therapy failed to improve the complete response rate or overall survival in patients with acute myeloid leukemia.This randomized phase 3 clinical trial evaluated the potential benefit of the addition of gemtuzumab ozogamicin (GO) to standard induction and postconsolidation therapy in patients with acute myeloid leukemia. Patients were randomly assigned to receive daunorubicin (45 mg/m 2 per day on days 1, 2, and 3), cytarabine (100 mg/m 2 per day by continuous infusion on days 1-7), and GO (6 mg/m 2 on day 4; DA1GO) vs standard induction therapy with daunorubicin (60 mg/m 2 per day on days 1, 2, and 3) and cytarabine alone (DA). Patients who achieved complete remission (CR) received 3 courses of highdose cytarabine. Those remaining in CR after consolidation were randomly assigned to receive either no additional therapy or 3 doses of GO (5 mg/m 2 every 28 days). From

A New Class of Antibody–Drug Conjugates with Potent DNA Alkylating Activity

“…However, identification of a suitable agent that meets the requirements for use as an effector molecule in ADCs, such as high in vitro potency, adequate water solubility, good stability in aqueous solutions, and achievement of a high therapeutic index remains a challenge. For example, ADCs carrying the potent DNA interacting agent calicheamicin are tolerated by humans only at very low doses and one such ADC, gemtuzumab ozogamicin, was withdrawn from the market due to a narrow therapeutic index and related safety concerns (15). ADCs of pyrrolobenzodiazepine (PBD) dimers, potent DNA cross-linkers, have recently been advanced into clinical evaluation (16)(17)(18).…”

Fludarabine, Cytarabine and Gentuzumab Ozogamicin (FLA-GO) as Salvage Therapy and Bridge to Transplant in Adult Relapsed Acute Myeloid Leukemia (AML) Patients

“…Even liver toxicity was negligible and no instances of SOS were observed in the overall population and in patients submitted to ASCT [31,[33][34][35][36]. Overall, ED rate was in line or even lower than what observed in other chemotherapy trials [8,25].…”

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

“…As with childhood ALL, the use of established chemotherapy drugs in improved combinations has gradually improved the cure rates in CBF AML from <50% to a range of 80-90% [11][12][13][14][15][16]. Historically, CBF AML was treated with standard cytarabine plus anthracycline induction chemotherapy followed by one or several consolidation courses of high-dose cytarabine.…”

“…Recent studies have used induction and consolidation courses of high-dose cytarabine in combination with fludarabine and idarubicin, as well as the addition of GO 3 mg/m 2 3 1 during induction and one consolidation course. These regimens, refining the use of old agents, were investigated in single arm and in comparative SWOG and MRC studies [11][12][13][14][15][16]. In the MD Anderson studies, the use of fludarabine with high-dose cytarabine and GO (or idarubicin) during induction and consolidations, the application of 4-6 consolidation courses, and modifying therapy for persistent MRD resulted in cure rates of 80% in both inversion 16 and t(8;21) AML (Fig.…”

“…Several studies then explored lower and fractionated dose schedules (GO 3 mg/m 2 3 1 during induction and consolidation; 3 mg/m 2 on Days 1, 4 and 7 of induction) in frontline randomized trials. The postapproval pivotal trial in the United States was conducted by SWOG (SWOG S0106) [16]. Patients were randomized to standard 3 1 7 with daunorubicin 60 mg/m 2 daily 3 3 versus the addition of GO 6 mg/m 2 on Day 4 to 3 1 7, but with a daunorubicin dose of 45 mg/m 2 daily 3 3.…”