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Combination Treatment Highly Effective for Long-Term Survival in Acute Promyelocytic Leukemia: Presented at ASH

By Bruce Sylvester

ORLANDO, FL -- December 12, 2006 -- Four-year follow-up data show significantly better outcomes among patients with acute promyelocytic leukemia (APL) if they are treated with front-line combination therapy with all-trans retinoic acid (ATRA) plus arsenic trioxide (As2O3), researchers reported here at the American Society of Hematology 48^th Annual Meeting and Exhibition (ASH).

"We saw dramatically improved clinical outcomes with this simple and convenient protocol," said lead investigator Sai-Juan Chen, MD, deputy director, Shanghai Institute of Hematology, Shanghai, China, in a media briefing on December 9^th. "We also saw significant improvement in the quality-of-life of our patients in the study."

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) and is found in 10% to 15% of all adult AML cases. APL prognosis has been poor, largely due to characteristic hemorrhagic complications, which can be aggravated by chemotherapy and lead to early death.

Since 1986, the use of ATRA to treat APL has dramatically improved clinical outcomes in China, with the complete rate of remission increasing to between 90% and 95% and 5-year overall survival to between 60% and 70%. Subsequently, AS203 has shown efficacy for both relapsed and newly diagnosed APL and has become standard therapy in China for relapsed patients with previous treatment of ATRA and/or chemotherapy.

But a sizable proportion of patients relapse and are resistant to treatment, the investigators noted. To further improve the clinical outcome of APL patients, they studied combination front-line use of ATRA and AS203.

For their study, the researchers enrolled 2 groups of patients with newly diagnosed APL -- 60 current patients enrolled since April 2001 and an historical cohort of 56 patients enrolled from May 1998 to March 2001 who were matched for sex, age, and hematological data at baseline.

Among the current cohort, all received 25 mg/m² ATRA orally and 0.16 mg/kg As2O3 IV every day until achieving complete remission (CR). Upon reaching CR, they received 3 courses of consolidation chemotherapy followed by 5 cycles of sequential treatment of ATRA, As2O3, and 6-mercaptopurine-plus-methotrexate.

Subjects in the historical group received ATRA 25mg/m² daily until reaching CR, and chemotherapy was added in case of leukocytosis.

As of the last follow-up in April 2006, 2 of the 56 subjects in the current cohort had undergone extramedullary relapse, and 1 of them also had a relapse in bone marrow. Both patients achieved and maintained a second CR with rescue treatment of ATRA/As2O3 and chemotherapy. A third patient died suddenly of suspected central nervous system leukemia. The other 53 patients remained alive and in hematologic remission.

With a median follow-up of 48 months (25-60 months), the 4-year overall survival rate was 98.1% and the event-free survival rate was 94.2%.

For the historical group with a median follow-up of 56 months (12-79 months), 4-year overall survival was 83.4% and event-free survival was 45.6%.

"These data clearly show the great benefit of front-line combination use of ATRA and AS2O3 in terms of survival," Dr. Chen said. "With more follow-up, we hope we can define a curative treatment for this disease."


[Presentation title: Long-Term Follow-Up Confirms the Benefit of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (As2O3) as Front Line Therapy for Newly Diagnosed Acute Promyelocytic Leukemia (APL). Abstract 565]

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