All-trans-retinoic acid in acute promyelocytic leukemia (North American Intergroup protocol)
N = 346
- Population
- Previously untreated APL (346 patients randomized to induction in the 1997 report; 350 in the 2002 long-term report)
- Design
- Randomized trial with two randomizations: induction with ATRA versus daunorubicin plus cytarabine; then, for patients still in complete remission after two consolidation cycles, maintenance with ATRA versus observation. Phase and primary endpoint are not stated in the abstract.
- Arms
- ATRA induction (experimental, n = 172): All-trans-retinoic acid as induction
- Chemotherapy induction (control, n = 174): Daunorubicin plus cytarabine as induction
- Chemotherapy, then observation (control): Induction with daunorubicin plus cytarabine, then observation
- Chemotherapy, then ATRA (experimental): Induction with daunorubicin plus cytarabine, then ATRA maintenance
- ATRA, then observation (experimental): ATRA induction, then observation
- ATRA, then ATRA (experimental): ATRA induction, then ATRA maintenance
- People
- Tallman MS, North American Intergroup
Δ Complete remission rate+3 pointsΔ 12-month OS+7 pointsΔ 12-month DFS+48 pointsΔ Complete remission rate−3 pointsΔ 60-month DFS+40 pointsΔ 60-month OS+24 points
Show the numbers
| Endpoint | Analysis | ATRA induction / Chemotherapy, then ATRA / ATRA, then observation / ATRA, then ATRA | Chemotherapy induction / Chemotherapy, then observation | Effect |
|---|---|---|---|---|
| Complete remission rate346 patients randomized to induction (172 ATRA, 174 chemotherapy) | primaryTallman 1997 | 72% | 69% | P=0.56124 of 172 versus 120 of 174 patients. |
| OSITT (the abstract states an intention-to-treat analysis), measured from study entry | primaryTallman 1997 | 82% at 12 mo; 72% at 2 y; 67% at 3 y | 75% at 12 mo; 57% at 2 y; 50% at 3 y | P=0.003 |
| DFSGroups defined by induction and maintenance assignment, as listed in the abstract; the abstract does not state which patients are included | primaryTallman 1997 | 77% at 12 mo; 61% at 2 y; 55% at 3 y | 29% at 12 mo; 18% at 2 y; 18% at 3 y | Disease-free survival estimates at one, two and three years when induction and maintenance treatments are taken into account together. The maintenance randomization applied to patients still in complete remission after consolidation. |
| Complete remission rate350 patients with newly diagnosed APL randomized | long term-updateTallman 2002 | 70% | 73% | Complete remission rates were not significantly different between the ATRA and daunorubicin-cytarabine groups, as stated in the abstract. |
| DFS350 patients with newly diagnosed APL randomized (analysis population not labelled in the abstract) | long term-updateTallman 2002 | 69% at 5 y | 29% at 5 y | — |
| OS350 patients with newly diagnosed APL randomized (analysis population not labelled in the abstract) | long term-updateTallman 2002 | 69% at 5 y | 45% at 5 y | — |
| DFSGroups defined by induction and maintenance randomizations, as listed in the abstract | long term-updateTallman 2002 | 47% at 5 y | 16% at 5 y | — |
| Endpoint | Analysis | ATRA induction / Chemotherapy, then ATRA / ATRA, then observation / ATRA, then ATRA | Chemotherapy induction / Chemotherapy, then observation | Effect |
|---|---|---|---|---|
| Complete remission rate346 patients randomized to induction (172 ATRA, 174 chemotherapy) | primaryTallman 1997 | 72% | 69% | P=0.56124 of 172 versus 120 of 174 patients. |
| OSITT (the abstract states an intention-to-treat analysis), measured from study entry | primaryTallman 1997 | 82% at 12 mo; 72% at 2 y; 67% at 3 y | 75% at 12 mo; 57% at 2 y; 50% at 3 y | P=0.003 |
| DFSGroups defined by induction and maintenance assignment, as listed in the abstract; the abstract does not state which patients are included | primaryTallman 1997 | 77% at 12 mo; 61% at 2 y; 55% at 3 y | 29% at 12 mo; 18% at 2 y; 18% at 3 y | Disease-free survival estimates at one, two and three years when induction and maintenance treatments are taken into account together. The maintenance randomization applied to patients still in complete remission after consolidation. |
| Complete remission rate350 patients with newly diagnosed APL randomized | long term-updateTallman 2002 | 70% | 73% | Complete remission rates were not significantly different between the ATRA and daunorubicin-cytarabine groups, as stated in the abstract. |
| DFS350 patients with newly diagnosed APL randomized (analysis population not labelled in the abstract) | long term-updateTallman 2002 | 69% at 5 y | 29% at 5 y | — |
| OS350 patients with newly diagnosed APL randomized (analysis population not labelled in the abstract) | long term-updateTallman 2002 | 69% at 5 y | 45% at 5 y | — |
| DFSGroups defined by induction and maintenance randomizations, as listed in the abstract | long term-updateTallman 2002 | 47% at 5 y | 16% at 5 y | — |
- ATRA induction (experimental)
- Chemotherapy induction (control)
Data table (modelled values)
| Months | ATRA induction | Chemotherapy induction |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 84.5% | 78.8% |
| 19 | 75.4% | 63.4% |
| 29 | 69.6% | 53.3% |
| 39 | 67.0% | 50.0% |
- Chemotherapy, then observation (control)
- Chemotherapy, then ATRA (experimental)
- ATRA, then observation (experimental)
- ATRA, then ATRA (experimental)
Data table (modelled values)
| Months | Chemotherapy, then observation | Chemotherapy, then ATRA | ATRA, then observation | ATRA, then ATRA |
|---|---|---|---|---|
| 0 | 100.0% | 100.0% | 100.0% | 100.0% |
| 10 | 36.4% | 80.4% | 78.6% | 88.2% |
| 19 | 18.8% | 66.6% | 63.6% | 77.9% |
| 29 | 18.0% | 57.8% | 60.0% | 75.0% |
| 39 | 18.0% | 55.0% | 60.0% | 75.0% |
Appears in
Sources
Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337(15):1021-8.
Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, et al. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood. 2002;100(13):4298-302.