Arsenic Trioxide Consolidation Therapy Improves Survival in Newly Diagnosed APL

ASCO—Arsenic trioxide (As2O3) should become a standard addition to front-line consolidation therapy in patients with acute promyelocytic leukemia (APL), Bayard L. Powell, MD, said at the plenary session of the American Society of Clinical Oncology 43rd Annual Meeting (abstract 2). Arsenic trioxide significantly improved survival and was particularly beneficial for APL patients at high risk of relapse because of initially high white blood cell (WBC) counts (more than 10,000 cells/mm3). The agent (Trisenox) is currently FDA approved for treatment of relapsed or recurrent APL.

The multi-institutional phase III trial included adult patients with APL who were in complete or partial first remission after induction therapy with oral all-trans-retinoic acid (tretinoin, ATRA), daunorubicin, and cytarabine. They were randomized to receive two consolidation courses of arsenic trioxide followed by standard consolidation with ATRA and daunorubicin (n = 243) or standard consolidation alone (n = 237).

Patients who remained in remission after consolidation therapy were further randomized to two different maintenance therapy arms, but there have been too few events to date to analyze these data, Dr. Powell commented.

Study Results

Compared with the standard consolidation arm, the arsenic-treated patients had significantly better 3-year event-free survival (81% vs 66%, P = .0007) and overall survival (86% vs 79%, P = .063), Dr. Powell reported. The addition of arsenic consolidation was associated with acceptable (and minimal additional) toxicity, he added.

Patients from all risk groups, based on initial WBC counts, gained from arsenic consolidation after remission. "Once patients achieve remission, the shapes of the event-free survival curves are very similar for each risk group," Dr. Powell said. The problem is that those in the high-risk group had fewer complete remissions, a higher risk of death during induction treatment, and more early relapses. "Arsenic trioxide overcomes the adverse effect of elevated WBC, but we need to change initial treatment for this group so that they can get to the point where they can benefit," Dr. Powell said.

He noted that "relapses were very uncommon in patients who actually received at least one dose of the planned arsenic trioxide consolidation therapy." There were only 5 relapses (2%) among these 202 patients.

"The differences in survival rates and relapse rates are great enough to justify including arsenic trioxide in standard first-line treatment," said Dr. Powell, who is professor of hematology and oncology at Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina. "Arsenic trioxide has already shown great benefits as a second-line treatment for APL, a cancer for which patients previously had few good treatment options. This study shows that even more patients will benefit if we give it earlier in the course of treatment."