Treating patients with high risk acute promyelocytic leukemia (APL) with ATRA, arsenic trioxide and gemtuzumab ozogamicin

The study evaluated the effectiveness and safety of combing all-trans retinoic acid (ATRA; Vesanoid), arsenic trioxide (ATO; Trisenox), and gemtuzumab ozogamicin (GO; Milotarg) in treating patients with high risk (HR) acute promyelocytic leukemia (APL). The authors found that the combination therapy was effective and well tolerated in these patients.

Patients with HR-APL have higher risks of death and relapse or cancer’s return after initial therapy, compared to stand risk (SR) APL. The combination of ATRA and ATO is well established for treating SR-APL, but not HR-APL. Adding the immunotherapeutic drug GO to ATRA+ATO was beneficial as an initial therapy in patients with HR-APL in a preliminary study. It is important to further validate its effectiveness in such patients.

The study included 70 adults with newly diagnosed HR-APL. All patients received ATRA+ATO+GO and were followed up for 3.4 years on average.

60 patients (86%) had complete remission (CR) after therapy. CR refers to the absence of all cancer symptoms. Patients reached CR after 39.5 days of therapy on average. 78% of patients were estimated to survive for 3 years without critical events. This is called event-free survival (EFS). EFS was improved compared to the known rate (50%) for such patients without ATRA+ATO+GO.

3-year rates of overall survival (OS) and relapse-free survival (RFS) were estimated at 86% and 91%. Relapse-related events occurred in 6 patients after 1.7 years of CR on average. The risk of relapse after 3 years of CR was 7.1%.

Molecular response (MR) refers to CR with the disappearance of the cancerous PML-RARα gene. MR data were available for 37 patients with CR. Among them, 22 were assessed within 8 weeks of diagnosis and 77% of them had MR. All of the rest 15 patients assessed after 8 weeks, achieved MR.

11% of patients died within 6 weeks of therapy. This was lower compared to known death rates (30%) in patients without this treatment. The most common side effects were high blood sugar, elevated liver enzymes indicating liver problems, headache, and fever with a lack of white blood cells.

The study concluded that combining ATRA, ATO, and GO was effective and tolerable for treating patients with HR-APL. 

The study was a small phase II trial. I also had no control group. Further larger studies are necessary to confirm these results.