All-Trans Retinoic Acid and Gemtuzumab Ozogamicin as Adjunct To Salvage Therapy in Primary Refractory Acute Myeloid Leukemia: Results of Consecutive Phase II Studies of the AMLSG.

Introduction: Response to first induction therapy is one of the most important prognostic factors in patients with adult myeloid leukemia (AML). Induction of CR or PR is the primary aim in these patients.

Methods: Between 1993 and 2005 225 consecutive patients (median age: 48.4 yrs, range 16–60 yrs) treated within the AMLHD93 (n=45), AMLHD98A (n=157) and AMLSG 05-04 (n=23, still active) trials were evaluated. All patients had primary refractory AML after one cycle of ICE. The different salvage therapies were as follows: AMLHD93 sequential-HAM (S-HAM) for patients <55 years of age [cytarabine 3g/m² bid. days 1,2,8,9, mitoxantrone 10mg/m² days 3,4,10,11], HAM for patients >=55 years of age [cytarabine 3g/m² bid., days 1–3, mitoxantrone 12mg/m² days 2,3]; AMLHD98A: A-HAM [HAM with ATRA 45mg/m² days 3–5, 15mg/m² days 6–28]; AMLSG 05-04: GO-A-HAM [A-HAM with gemtuzumab ozogamicin 3g/m² day 1].

Results: The distribution of the different salvage therapies was HAM n=21, S-HAM n=22, A-HAM n=117, GO-A-HAM n=23, other n=31 no further therapy n=11. Response according to salvage therapy was as follows:

No CTC-grade 3-5 liver toxicity was seen in patients receiving GO-A-HAM. Multivariable analyses revealed that regimens containing ATRA (odds ratio 2.5, p=0.01) and cytogenetic subgroup [t(11q23) odds ratio 4.2 p=0.04 (n=13), non-complex high risk aberrations odds ratio 4.2 p=0.007 (n=34)] were associated with a significantly better response rate (subsuming CR and PR). 119 of 225 patients have received stem cell transplantation. No case of veno occlusive disease was in 10 so far transplanted pts who have had GO-A-HAM. Median survival was 10.7 months.

Conclusions: Although retrospective in nature our study suggests that ATRA as adjunct to salvage chemotherapy in primary refractory AML patients improves the response rate. The addition of GO in a dosage of 3mg/m² results in promising response rates without increasing toxicity.