Chemo-free approach helpful in promyelocytic leukemia

Last Updated: 2015-10-07

By David Douglas

NEW YORK (Reuters Health) - In patients with acute myeloid leukemia, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) treatment has advantages over the standard chemotherapy-based regimen, according to UK researchers.

As Dr. Alan K. Burnett told Reuters Health by email, the study endorses previous findings showing that "the 'chemo-free' option of ATRA and ATO can cure low-risk acute promyelocytic leukemia, and makes some additional points."

In a paper online September 16 in The Lancet Oncology, Dr. Burnett of the University of Heath Park in Cardiff and colleagues report on their findings in 235 patients who were randomly assigned to ATRA and idarubicin or ATRA and ATO. The ATO regimen involved higher doses administered on fewer days than in previous studies.

Neither maintenance treatment nor CNS prophylaxis was given to patients in either group but certain high-risk patients were eligible to receive an initial dose of the immunoconjugate gemtuzumab ozogamicin.

Median follow-up lasted about 2.5 years. Quality of life did not differ significantly between the treatment groups. However, more patients in the chemotherapy group (57/119) reported grade 3-4 toxicities than in the ATRA and ETO group (40/116). Corresponding proportions for grade 3-4 alopecia were 23% and 5% and for oral toxicity, they were 19% and 1%.

Overall, patients in the ATRA and ATO group, the researchers say, "had significantly less requirement for most aspects of supportive care than did those in the ATRA and idarubicin group."

The ATRA and ATO approach, Dr. Burnett said, "is feasible and effective in high-risk disease with a single injection of gemtuzumab ozogamicin on day 1. Once in molecular remission there have been no relapses, so these patients no longer need regular minimal residual-disease monitoring."

Dr. Burnett concluded that "our schedule involved half the number of ATO injections as the (earlier) trial and was associated with minimal liver toxicity and significantly less supportive care than existing standard of care."

Overall, the team concludes that "a de-escalation of therapy in this disease can be implemented, with an associated high cure rate above 90%, without affecting quality of life."

Commenting on the findings by email, Dr. Farhad Ravandi-Kashani, co-author of an accompanying editorial, told Reuters Health the "study confirms prior studies that have shown feasibility and superior efficacy of ATRA-plus-arsenic regimen in the initial therapy of patients with standard-risk APL (approximately two-thirds of the patients). But more importantly, it demonstrates the efficacy of the combination with added gemtuzumab ozogamicin in patients with high-risk disease."

Dr. Ravandi-Kashani, of the University of Texas MD Anderson Cancer Center in Houston, added, "It also demonstrates the possibility of delivering arsenic trioxide on a twice per week basis."

SOURCE: http://bit.ly/1VDd3qs and http://bit.ly/1Rtu9RQ

Lancet Oncol 2015.