Do We Require Chemotherapy to Cure Acute Promyelocytic Leukemia? - - PowerPoint PPT Presentation

Do We Require Chemotherapy to Cure Acute Promyelocytic Leukemia?

Miguel A. Sanz Chairman, Spanish PETHEMA Group University Hospital La Fe Valencia, Spain

The 1st World Congress on Controversies in Hematology

Rome, Italy (September 3rd, 2010)

Curability of APL without Chemotherapy (or with minimal use of chemotherapy)

Long-lasting remissions have been reported with: ­ Liposomal ATRA alone (MDACC) ­ Arsenic trioxide ± ATRA (China, Iran, India, MDACC) ­ ATRA followed by maintenance chemotherapy

Do We Require Chemotherapy to Cure Acute Promyelocytic Leukemia?

No, but…

is this the appropriate question?

Do We Require Chemotherapy to Achieve a Higher Cure Rate in Acute Promyelocytic Leukemia?

Yes

Current Standard Approach ATRA + anthracycline-based chemotherapy The available data do not suggest any advantage of ATO when compared with chemotherapy

The use of ATO should be restricted to:

˗ Patients unfit for chemotherapy ˗ Clinical trials

Is Arsenic Trioxide a Real Alternative to Chemotherapy?

ATO should be evaluated in proper comparisons with the standard approach in terms of: – Efficacy – Safety – Cost-effectiveness The challenge is to demonstrate a significant superiority in terms of efficacy and/or safety.

Direct Costs of Antileukemic Drugs for a Standard Patient with APL

10000 20000 30000 40000 50000 I n d u c t i

• n

C

• n

s

• l

1 C

• n

s

• l

2 C

• n

s

• l

3 T

• t

a l

Cost in Euros

ATRA Idarubicin ATO

Patient: 1.8 m2 (70 kg)

Induction Therapy with AIDA

Causes of failure (n = 739)

Hemorrhage (5%) Infection (2.3%) RAS (1.3%) Other (0.3%)

Death 9% CR 91%

De la Serna et al. Blood 2008

Room for improvement

Virtual absence

• f resistance

Post-remission Outcome with AIDA

Causes of failure

CR 91%

Sanz et al. Blood 2010 Montesinos et al. J Clin Oncol 2010

Room for improvement

• Death in CR: < 1%
• Relapse (CIR at 5 years): 7%

˗ Low risk: 4% (20% of APL patients) ˗ Intermediate risk: 6% ˗ High risk: 11% (25% of APL patients) ˗ Therapy-related AL/MDS (CI at 6 years): 2.2% ˗ Late cardiotoxicity: ?

How many patients are needed to demonstrate a significant benefit of these outcomes?

Are Treatment Options for APL Mutually Exclusive?

• GIMEMA trial

– WBC ≤10x109/L: standard approach (AIDA) vs. ATO-

based approach (MDACC)

– WBC >10x109/L: standard approach

• BNCRI trial

– standard approach (AIDA) vs. ATO-based approach

(MDACC)

Ongoing Studies Exploring the Replacement of Chemotherapy by ATO

Are Treatment Options for APL Mutually Exclusive? They are complementary options

Studies Exploring the Complementary Use of Chemotherapy and ATO

• French-Belgian-Swiss Trial (ongoing)

– WBC ≤10x109/L: ATRA vs. Ara-C vs. ATO in consolidation – WBC >10x109/L: Ara-C vs. Ara-C + ATO in consolidation

• PETHEMA/HOVON planned trial

– Insert 2 cycles of ATO + ATRA in a standard consolidation