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All-trans retinoic acid plus arsenic trioxide ‘noninferior’ to chemotherapy-based regimen

By Lynda Williams, medwireNews Reporter

Findings from The Children’s Oncology Group AAML1331 study suggest that all-trans retinoic acid (ATRA) and arsenic trioxide may be able to reduce or eliminate the need for cytotoxic chemotherapy in children and young adults with a new diagnosis of acute promyelocytic leukaemia (APL).

Matthew Kutny, from the University of Alabama at Birmingham, USA, and co-workers report in JAMA Oncology that the survival outcomes of the study “met noninferiority criteria” when compared with historical data for patients who received anthracycline-containing chemotherapy.

They point out that the ATRA regimen has additional advantages, “including shorter treatment duration, lower exposure to anthracycline and intrathecal chemotherapy, and fewer days in the hospital.”

Recognising that ATRA plus arsenic trioxide is effective for adult patients with standard-risk APL, the team investigated whether the combination is also effective for patients aged 1–21 years (median 14.4 years) with newly diagnosed standard- or high-risk APL, defined as a white blood cell count of less than 10,000/µL or 10,000/µL and above, respectively.

Of 154 participants (52.6% male) diagnosed at institutions in Australia, Canada and the USA between 2015 and 2019, 63.6% had standard-risk APL and 36.4% had high-risk APL.

The standard-risk APL patients were given induction therapy consisting of ATRA 12.5 mg/m2 twice daily plus once-daily arsenic trioxide 0.15 mg/kg for 28–70 days; the high-risk APL patients were given the same induction regimen plus four doses of idarubicin 12.0 mg/m2 on days 1, 3, 5 and 7, plus twice daily dexamethasone 2.5 mg/m2 on days 1–14.

Both groups then received four cycles of ATRA plus arsenic trioxide consolidation therapy but no maintenance treatment, say Kutny and co-workers.

All patients achieved complete haematological remission or complete remission with incomplete haematological recovery within 70 days (median duration of treatment 47 days).

Patients with standard-risk APL had a 2-year event-free survival rate of 98.0% and an overall survival rate of 99.0%, with corresponding rates of 96.4% and 100.0% in the high-risk APL patients.

These survival outcomes were compared with historical data for newly diagnosed APL patients who participated in the AAML0631 study and received consolidation therapy with two 5-week arsenic trioxide cycles plus anthracycline chemotherapy.

The survival outcomes of the current AAML1331 trial met the predefined noninferiority criteria of 10% for standard-risk APL and 14.5% for high-risk APL, the team emphasizes.

One (1.1%) standard-risk patient experienced molecular bone marrow relapse but was alive after at least 3.5 years of follow-up from diagnosis and further treatment with chemotherapy and autologous stem cell transplantation.

Two (3.9%) high-risk APL patients experienced relapse at 2 years, with one patient alive after 3.5 years after diagnosis following molecular relapse and a second patient alive at approximately 3 years after diagnosis after bone marrow relapse requiring chemotherapy and allogenic stem cell transplantation.

“The study results confirmed that pediatric patients with standard-risk APL could be safely treated with ATRA/arsenic trioxide therapy and could achieve results similar to those in adult patients, for which this treatment has become the preferred regimen”, write Kutny and co-authors.

“We also found the best outcomes to date among a large group of patients with high-risk APL”, they say.

The researchers conclude: “The novel treatment regimen for those with high-risk APL, which included limited use of anthracycline (during induction therapy only) without other cytotoxic chemotherapy and shortened treatment duration without the use of maintenance therapy, set a new standard for the treatment of childhood APL.”

News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Oncol 2022; doi10.1001/jamaoncol.2021.5206