Molecular response with long-term follow-up
| Trial . | Study arms . | No. of patients . | Median follow-up . | EMR at 3 mo . | CCyR by 12 mo . | MMR 12 mo*,† . | MMR by 2 y . | MR4 by 2 y . | MR4.5 by 2 y . | MR4 by 5 y . | MR 4.5 by 5 y . | MR4 by 10 y . | MR4.5 by 10 y . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IRIS‡ | Imatinib (400 mg) | 553 | 11 y | — | 69%* | 39%* | — | — | — | — | 40.2%§ | — | 63.2%§ |
| Interferon/cytarabine | 553 | — | — | — | — | — | — | — | — | ||||
| German CML Study IV | Imatinib (400 mg) arm (all) | 400 (1551) | 9.5 y | 68.5%|| | 67.5% | 36.7% | — | — | — | 65.7% | 49.4% | 81% | 67.2% |
| DASISION¶ | Dasatinib (100 mg) | 259 | 5 y | 84% | 83.0% | 46.0% | 64.0% | — | 17.0% | — | 42.0% | — | — |
| Imatinib (400 mg) | 260 | 64% | 72.0% | 28.0% | 46.0% | — | 8.0% | — | 33.0% | — | — | ||
| ENESTnd# | Nilotinib 300 mg twice daily | 282 | 5 y | 91% | 80.0% | 44%† | 71.0% | 39.0% | 25.0% | 65.6% | 53.5% | 73% | 64% |
| Nilotinib 400 mg twice daily | 281 | 89% | 78.0% | 43%† | 67.0% | 33.0% | 19.0% | 63.0% | 52.3% | — | — | ||
| Imatinib (400 mg) | 283 | 67% | 65.0% | 22%† | 44.0% | 18.0% | 9.0% | 41.7% | 31.4% | 56% | 44% | ||
| BFORE#,** | Bosutinib (400 mg) | 268 | 2 y | 75% | 77.2% | 47.2%† | 61.2% | 32.8% | 13.1% | — | — | — | — |
| Imatinib (400 mg) | 268 | 57% | 66.4% | 36.9%† | 50.7% | 25.7% | 10.8% | — | — | — | — |
| Trial . | Study arms . | No. of patients . | Median follow-up . | EMR at 3 mo . | CCyR by 12 mo . | MMR 12 mo*,† . | MMR by 2 y . | MR4 by 2 y . | MR4.5 by 2 y . | MR4 by 5 y . | MR 4.5 by 5 y . | MR4 by 10 y . | MR4.5 by 10 y . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IRIS‡ | Imatinib (400 mg) | 553 | 11 y | — | 69%* | 39%* | — | — | — | — | 40.2%§ | — | 63.2%§ |
| Interferon/cytarabine | 553 | — | — | — | — | — | — | — | — | ||||
| German CML Study IV | Imatinib (400 mg) arm (all) | 400 (1551) | 9.5 y | 68.5%|| | 67.5% | 36.7% | — | — | — | 65.7% | 49.4% | 81% | 67.2% |
| DASISION¶ | Dasatinib (100 mg) | 259 | 5 y | 84% | 83.0% | 46.0% | 64.0% | — | 17.0% | — | 42.0% | — | — |
| Imatinib (400 mg) | 260 | 64% | 72.0% | 28.0% | 46.0% | — | 8.0% | — | 33.0% | — | — | ||
| ENESTnd# | Nilotinib 300 mg twice daily | 282 | 5 y | 91% | 80.0% | 44%† | 71.0% | 39.0% | 25.0% | 65.6% | 53.5% | 73% | 64% |
| Nilotinib 400 mg twice daily | 281 | 89% | 78.0% | 43%† | 67.0% | 33.0% | 19.0% | 63.0% | 52.3% | — | — | ||
| Imatinib (400 mg) | 283 | 67% | 65.0% | 22%† | 44.0% | 18.0% | 9.0% | 41.7% | 31.4% | 56% | 44% | ||
| BFORE#,** | Bosutinib (400 mg) | 268 | 2 y | 75% | 77.2% | 47.2%† | 61.2% | 32.8% | 13.1% | — | — | — | — |
| Imatinib (400 mg) | 268 | 57% | 66.4% | 36.9%† | 50.7% | 25.7% | 10.8% | — | — | — | — |
Data from 4 first-line phase 3 randomized registration studies (IRIS, DASISION, ENESTnd, and BFORE) and the first-line imatinib 400 mg daily arm of the German CML Study IV are shown. MRs at various time points are shown. These trials cannot be directly compared, because different methods of trial evaluation were used (eg, rates at a specific time point vs cumulative incidence estimates).
CCyR, complete cytogenetic response (no Philadelphia chromosome–positive metaphases by bone marrow examination); EMR, early molecular response; MMR, major molecular response; MR, molecular response.
Estimated rate.
†Rate at 12 months (ie, not cumulative).
‡The primary endpoint for IRIS was event-free survival (survival without transformation to accelerated phase/blast phase, loss of complete hematologic response, loss of major cytogenetic response, or increased white blood cell count); survival outcomes include 363 patients who crossed over to imatinib.
Rate at the specific time point (eg, at 5 years and at 10 years).
Includes all patients in all arms.
The primary endpoint for the DASISION study was confirmed complete cytogenetic response by 12 months.
The primary endpoint of the ENESTnd and BFORE studies was MMR rate at 12 months.
Twenty-four-month BFORE trial updates have been presented in abstract format.41