Platzbecker U et al. Proc ASH 2014;Abstract 12.

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Presentation transcript:

Platzbecker U et al. Proc ASH 2014;Abstract 12. Improved Outcome with ATRA-Arsenic Trioxide Compared to ATRA-Chemotherapy in Non-High Risk Acute Promyelocytic Leukemia — Updated Results of the Italian-German APL0406 Trial on the Extended Final Series Platzbecker U et al. Proc ASH 2014;Abstract 12.

Background Results from the Phase III APL0406 trial showed that the combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior and possibly superior to standard ATRA and chemotherapy (CHT) in the front-line management of low-to intermediate-risk acute promyelocytic leukemia (APL) (NEJM 2013;369(2):111-21): 2-year event-free survival (EFS): 97% (ATRA-ATO) vs 86% (ATRA-CHT); p < 0.001 for noninferiority and p = 0.02 for superiority 2-year overall survival (OS): 99% (ATRA-ATO) vs 91% (ATRA-CHT); p = 0.02 Study objective: To report the updated efficacy results from the extended and final series of 276 patients with newly diagnosed nonhigh-risk APL. Platzbecker U et al. Proc ASH 2014;Abstract 12.

Phase III APL0406 Trial Design Eligibility (n = 276) Newly diagnosed APL Age 18 to <71 years Low to intermediate risk WBC at diagnosis: ≤10 x 109/L ATRA-ATO R ATRA-CHT ATRA: 45 mg/m2 per day; ATO: 0.15 mg/kg per day Patients on the ATRA-ATO arm received ATRA-ATO induction until complete response (CR), then ATO 5 days/week, 4 weeks on, 4 weeks off for a total of 4 courses and ATRA 2 weeks on, 2 weeks off for a total of 7 courses. Patients on the ATRA-CHT arm received the standard ATRA + idarubicin induction followed by 3 cycles of anthracycline-based consolidation together with ATRA and low-dose CHT and ATRA for maintenance. Primary endpoint: 2-year EFS Platzbecker U et al. Proc ASH 2014;Abstract 12; LoCoco F et al. N Engl J Med 2013;369(2):111-21.

Survival Outcomes Outcome ATRA-ATO (n = 122) ATRA-CHT (n = 132) p-value Two-year EFS 98% 84.9% 0.0002 Two-year cumulative incidence of relapse 1.1% 9.4% 0.005 Two-year OS 99.1% 94.4% 0.01 Median follow-up period = 36 months. Four patients died during induction therapy on the ATRA-CHT arm. Platzbecker U et al. Proc ASH 2014;Abstract 12 (Abstract only).

Response to Induction Therapy ATRA-ATO (n = 122)* ATRA-CHT (n = 132)* p-value CR rate 100% 97% 0.12 * Number of patients evaluable for response to induction Platzbecker U et al. Proc ASH 2014;Abstract 12 (Abstract only).

Author Conclusions The data on this extended cohort demonstrate a significantly augmented survival benefit coupled to a higher antileukemic efficacy provided by ATRA-ATO compared to ATRA-CHT for patients with low- to intermediate-risk APL. These results further support ATRA-ATO as the new standard therapy in this clinical setting. Platzbecker U et al. Proc ASH 2014;Abstract 12 (Abstract only).

Investigator Commentary: Updated Results of the APL0406 Trial of ATRA-ATO versus ATRA-CHT in Newly Diagnosed APL The original results of the APL0406 trial were presented at a plenary session at ASH 2012 and were published in 2013. I believe that the updated results are practice changing. Patients had to have low- to intermediate-risk APL to be eligible. Neither of the treatment arms included cytarabine, which continues to be somewhat controversial in the treatment of APL. The primary endpoint was EFS at 2 years. When the results were initially presented the median follow-up was 2 years, and we thought the results were provocative but we were eager to see the data after a longer follow-up period. With 3 years of follow- up the CR rate is 100% with ATRA-ATO versus 97% with ATRA-CHT. These results were not statistically different. Four patients died on the ATRA-CHT arm. The CR rate for APL is higher than 90%. Those patients who do not achieve a CR die: There is no middle ground in APL. The 2- year EFS and OS rates were 98% and 99% with ATRA-ATO versus 84.9% and 94.4% with ATRA-CHT. Based on these data, our standard for patients with lower-risk APL at the Cleveland Clinic is induction ATRA-ATO in postremission therapy, and we exclude chemotherapy altogether. We did not make this change after the initial presentation because we were not convinced by the results after just 2 years of follow-up. Interview with Mikkael A Sekeres, MD, MS, January 20, 2015