All-Oral Regimen Demonstrates Survival Benefits, Safety in AML Subset

Treatment with an all-oral regimen of arsenic trioxide, all-trans retinoic acid (ATRA) and ascorbic acid (AAA) demonstrated benefits to patients with acute promyelocytic leukemia (APL), according to findings from a trial that were presented at the 2023 ASH Annual Meeting.

Specifically, the researchers noted that the three treatments led to three-year overall survival (percentage of patients who are still alive after a specific amount of time) and relapse-free survival (length of time after primary treatment when a patient lives without signs of cancer) rates of 97% in the patient population.

“Use of an entirely oral AAA-based induction in a risk-adapted strategy that mitigated chemotherapy was highly effective and safe in newly diagnosed APL of all risk categories and all ages,” lead study author Dr. Harinder Gill, Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong in China, said in a press conference during the meeting.

According to the National Cancer Institute, ACP is a fast-growing subset of acute myeloid leukemia, which is when there are too many immature blood-forming cells in both the blood and bone marrow.

Researchers reported that remission rates over 90% are common with ATRA and intravenous arsenic trioxide plus chemotherapy or ATRA and chemotherapy. However, the rate of relapse falls between 5% and 10%, reaching as high as 20% with conventional ATRA and chemotherapy.

Despite the relatively high rate of long-term survival, early death remains an issue for patients globally without access to arsenic trioxide, most commonly in resource-constrained countries. Although chemotherapy is an integral part of treatment, there is a need to reduce chemotherapy to lessen the rate of short- and long-term toxicities.

As such, investigators evaluated the efficacy and safety of an all-oral AAA-induction regimen in a risk-adapted strategy with no chemotherapy and minimal chemotherapy in low-risk and high-risk patients with APL.

Between Jan. 1, 2018, and Sept. 30, 2023, 51 men and 74 women were enrolled. The median patient age was 49 years, although five patients were under the age of 18. Most patients (93 patients) were at standard risk and 32 patients were at high risk. Eight patients had early deaths (intracerebral hemorrhage, six patients; APL differentiation syndrome [APL-DS], two patients); these patients were treated off protocol with oral AAA.

Overall, 117 patients received oral AAA-based induction on protocol, 92 (78.6%) received AAA alone and 25 (21.4%) received AAA in combination with daunorubicin.

Molecular responses of the all-oral induction, consolidation, and maintenance regimen were also evaluated. At a median follow-up of 31 months, results showed that all patients on the oral regimen treated on protocol achieved complete response.

At the time of data censoring, 63 patients had completed two years of oral AAA maintenance. Regarding fatality, one relapse leading to death occurred from refractory APL and one death in CR1 occurred due to an unrelated cause.

Regarding safety, the most frequent non-blood toxicity was transaminitis (increased levels of certain liver enzymes in the blood; 49.6%) and headache (36%). Neither cardiotoxicity nor grade 3 or grade 4 hepatotoxicity (impairment of the liver function) related to oral arsenic trioxide occurred, nor did treatment discontinuations due to oral arsenic trioxide. Of note, no treatment-related deaths occurred.

Among patients who received AAA, APL-DS occurred in 68 patients after beginning AAA, all within the first 14 days, and all fully responsive to dexamethasone (a drug that reduces inflammation and lowers the body’s immune responses).

The regimen will be further evaluated in a multicenter setting in Asia, and a pivotal trial is planned.

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