Chemo-Free Treatment Effective in Kids With Aggressive Blood Cancer

A chemotherapy-free regimen was safe and effective in pediatric patients with newly diagnosed acute promyelocytic leukemia (APL), according to results from a prospective study.

The 2-year overall survival (OS) rate among all 114 patients in the study was 99.1%, reported Franco Locatelli, MD, PhD, of IRCCS Bambino Gesù Children’s Hospital in Rome, during a session at the European Hematology Association annual congress in Stockholm.

The 2-year OS rates were 100% for standard-risk patients who received all-trans retinoic acid and arsenic trioxide and 97.4% for high-risk patients who also received gemtuzumab ozogamicin (Mylotarg).

In addition, 2-year event-free survival rates were 96.9% in the overall cohort, 98% in standard-risk patients, and 94.3% in high-risk patients.

Locatelli observed that the survival outcomes seen in this trial — ICC-APL-02 — were better than those reported in ICC-APL-01, which tested a risk-adapted combination of all-trans retinoic acid and chemotherapy in newly diagnosed pediatric patients with this rare, aggressive subtype of acute myeloid leukemia.

“We confirmed that ATRA/ATO [all-trans retinoic acid and arsenic trioxide] treatment is safe and effective in standard-risk patients,” Locatelli noted. “More importantly, the combination of ATRA, ATO, and gemtuzumab showed an excellent safety profile and unprecedented efficacy in high-risk pediatric patients with de novo APL. Overall, we think that this study has now established the new standard of care for treating children with de novo APL.”

He pointed out that the introduction of all-trans retinoic acid and arsenic trioxide has revolutionized the treatment of APL, leading to the use of chemotherapy-free protocols in standard-risk adult patients.

While several studies have evaluated all-trans retinoic acid and arsenic trioxide in pediatric patients with newly diagnosed APL, Locatelli said that none of them have been completely chemotherapy free.

Thus, this study represented the first large, multicenter, prospective pediatric trial that delivered a non-chemotherapy-based treatment for children and adolescents with newly diagnosed standard- and high-risk APL, he added.

ICC-APL-02 was conducted at 52 centers in five countries (Italy, France, Czech Republic, Netherlands, and Sweden), and included 114 patients (38 with high-risk APL and 76 with standard-risk APL). Median age was 13 years, and 53.5% were male.

During induction, arsenic trioxide was given at a dose of 0.15 mg/kg/day intravenously and all-trans retinoic acid was given at a dose of 25 mg/m²/day orally. Treatment started on day 1 and was continued until hematological complete remission was achieved. In high-risk patients only, gemtuzumab ozogamicin was administered on days 2 and 4 of induction treatment.

During consolidation, arsenic trioxide was given at the same dose employed during induction for 5 days a week, 4 weeks on and 4 weeks off, for 4 courses, while all-trans retinoic acid was administered 2 weeks on and 2 weeks off for 7 courses. In the high-risk group only, triple intrathecal therapy was administered at the beginning of the first and third consolidation courses.

Median duration of induction was 38 days (range 28-60), and one-third of patients experienced a transient treatment interruption (median duration 5 days), mainly due to differentiation syndrome (41.2%), pseudotumor cerebri (12.3%), and prolongation of the QTc interval (11.4%).

All but one patient achieved minimal residual disease (MRD) negativity by the end of the third consolidation course. That patient (who had high-risk disease) remained MRD-positive after the end of treatment, then obtained molecular remission with two additional doses of gemtuzumab ozogamicin, and eventually underwent autologous hematopoietic stem cell transplantation, and is now alive and disease-free.

A standard-risk patient had molecular relapse 1 year after completing the treatment protocol, then underwent a new treatment with all-trans retinoic acid and arsenic trioxide and is now alive with MRD negativity.

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