AHL 2011: A Lysa randomized phase III study of a treatment driven by early PET response compared to a standard treatment in patients with Ann Arbor stage III-IV or high-risk IIB Hodgkin lymphoma.

Abstract

TPS8615 Background: ABVD is the most widely chemotherapy regimen used as standard treatment of advanced Hodgkin lymphoma (HL). The escalated BEACOPP (BEAesc) regimen which delivers more drugs at higher dose intensity was shown to improve patient’s PFS but not OS when compared to ABVD (Federico M, 2009; Viviani S, 2011; Carde P, 2012). The better efficiency of BEAesc is associated to a marked immediate hematologic toxicity and a higher risk of secondary myelodysplasia/leukemia. Also, the gonadal toxicity which is a real concern in young women, is quite higher when using BEAesc. So, to better manage HL treatment we need to identify early responding patients able to benefit from a strategy of dose intensity decrease after upfront BEAesc, without impairing the disease control. PET performed after 2 cycles of chemotherapy (PET2) might identify such a population suitable for receiving ABVD after 2 cycles of upfront BEAesc, and was implemented in the present study. Methods: The AHL 2011 trial (NCT01358747) was designed to test in 16 to 60 years old HL patients with Ann Arbor stage III, IV or high risk IIB, a treatment strategy driven by PET after 2 cycles of BEACOPPesc, delivering 4 cycles of ABVD for PET2 negative patients and 4 cycles of BEAesc for PET2 positive patients, compared to a treatment not monitored by PET, delivering the best BEAesc schedule consisting in 6 cycles of this regimen (Engert A, 2012). A baseline PET is mandatory before treatment and PET2 are centrally reviewed within 48 hours and interpreted according to Deauville criteria. The allocation of treatment in the experimental arm is based on the PET2 central review result. PFS is the primary endpoint of the study with an hypothesis of non-inferiority of the experimental arm with a margin of 10% (85% 5y-PFS in the control arm vs >75% in the experimental arm). With a 6-year of accrual period, inclusion of 405 patients in each arm would have 80% power to detect a HR of 1.77 using a one-sided log rank test with significance level of 0.025. The trial started in May 2011 and to date, 385 patients have been enrolled. The DSMC reviewed the trial in November 2012 and suggested that the trial continue as planned. Clinical trial information: NCT01358747.