TY - JOUR
T1 - Long-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia
AU - Jen, Wei Ying
AU - Marvin-Peek, Jennifer
AU - Kantarjian, Hagop M.
AU - Alvarado, Yesid
AU - Borthakur, Gautam
AU - Jabbour, Elias
AU - Wierda, William
AU - Kadia, Tapan M.
AU - Daver, Naval G.
AU - DiNardo, Courtney D.
AU - Short, Nicholas J.
AU - Jain, Nitin
AU - Ferrajoli, Alessandra
AU - Kornblau, Steven
AU - Yilmaz, Musa
AU - Ohanian, Maro
AU - McCue, David
AU - Burger, Jan
AU - Hammond, Danielle
AU - Patel, Keyur
AU - Issa, Ghayas C.
AU - Pemmaraju, Naveen
AU - Sasaki, Koji
AU - Maiti, Abhishek
AU - Abbas, Hussein A.
AU - Chien, Kelly
AU - Takahashi, Koichi
AU - Haddad, Fadi
AU - Bose, Prithviraj
AU - Masarova, Lucia
AU - Montalban-Bravo, Guillermo
AU - Swaminathan, Mahesh
AU - Brandt, Mark
AU - Pierce, Sherry
AU - Garcia-Manero, Guillermo
AU - Ravandi, Farhad
N1 - Publisher Copyright:
© 2024 American Cancer Society.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL. Methods: This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6–9 mg/m2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 109/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence. Results: One hundred forty-six patients (median age, 53.0 years; range, 19.3–83.9 years) were treated, including 106 patients (72.6%) with standard-risk APL and 40 (27.4%) with high-risk APL. GO was administered to 68 standard-risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%–98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow-up of 61.8 months (95% CI, 4.7–128.4 months), the 5-year event-free survival, disease-free survival, and overall survival rates were 92.4% (95% CI, 87.9%–97.1%), 93.6% (95% CI, 89.5%–97.8%), and 93.1% (95% CI, 88.9%–97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno-occlusive disease. Conclusions: The combination of ATO-ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161).
AB - Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL. Methods: This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6–9 mg/m2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 109/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence. Results: One hundred forty-six patients (median age, 53.0 years; range, 19.3–83.9 years) were treated, including 106 patients (72.6%) with standard-risk APL and 40 (27.4%) with high-risk APL. GO was administered to 68 standard-risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%–98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow-up of 61.8 months (95% CI, 4.7–128.4 months), the 5-year event-free survival, disease-free survival, and overall survival rates were 92.4% (95% CI, 87.9%–97.1%), 93.6% (95% CI, 89.5%–97.8%), and 93.1% (95% CI, 88.9%–97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno-occlusive disease. Conclusions: The combination of ATO-ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161).
KW - acute promyelocytic leukemia (APL)
KW - all-trans retinoic acid (ATRA)
KW - arsenic trioxide (ATO)
KW - clinical trial
KW - gemtuzumab ozogamicin (GO)
UR - http://www.scopus.com/inward/record.url?scp=85210070785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85210070785&partnerID=8YFLogxK
U2 - 10.1002/cncr.35662
DO - 10.1002/cncr.35662
M3 - Article
C2 - 39584789
AN - SCOPUS:85210070785
SN - 0008-543X
VL - 131
JO - Cancer
JF - Cancer
IS - 1
M1 - e35662
ER -