Table 2.
Patient Characteristics Among Newly Diagnosed Imatinib-Treated CML
| Characteristic | Optimal | Suboptimal | Resistant |
|---|---|---|---|
| Total patients | |||
| First set | 41 | 7 | 20 |
| Second set | 43 | 15 | 10 |
| Median age, years | |||
| First set | 46 | 51 | 36 |
| Range | 21-70 | 34-71 | 20-60 |
| Second set | 45 | 40 | 40 |
| Range | 18-77 | 24-71 | 32-84 |
| Stage at start of imatinib | |||
| First set | |||
| CP | 34 | 6 | 14 |
| AP | 7 | 1 | 6 |
| Second set | |||
| CP | 38 | 13 | 9 |
| AP | 5 | 2 | 1 |
| Median BCR-ABL1/ABL1 QRT-PCR, % | |||
| First set | 90.9 | 65.6 | 30.2 |
| Second set | 45.0 | 45.2 | 43.6 |
| Clonal evolution at presentation | |||
| First set | 6 | 1 | 4 |
| % | 15 | 14 | 20 |
| Second set | 2 | 0 | 1 |
| % | 5 | 10 | |
| Median imatinib dose over first year, mg/d | |||
| First set | 700* | 500† | 500‡ |
| Second set | 600 | 600 | 500 |
| Median follow-up (range, months) | |||
| First set | 45.0 | 43.3 | 35.0 |
| Range | 12-60.1§ | 15.4-54.3‖ | 7.3-55.4¶ |
| Second set | 60.9 | 60.9 | 43.6 |
| Range | 14.8-94.8 | 24.5-113.7 | 23.4-109.5 |
| Outcome first and second set combined | 3 DOD, 1 DOOD | 1 DOOD | 4 DOD, 2 DOOD |
| Hematologic parameters in first set | |||
| Median presenting WBC, ×109/L | 77 | 75.9 | 81 |
| Median presenting platelet count, ×109/L | 296 | 337 | 467 |
| Elevated PB blasts, > 5% | 2 | 1 | 5 |
| Elevated PB basophils, > 5% | 6 | 3 | 5 |
| Splenomegaly at presentation | 8 | 1 | 8 |
| Sokal risk score# | |||
| Low | 30 | 5 | 11 |
| Intermediate | 9 | 2 | 1 |
| High | 1 | 6 |
Abbreviations: CML, chronic myelogenous leukemia; CP, chronic phase; AP, accelerated phase; QRT-PCR, quantitative reverse transcription polymerase chain reaction; DOD, died of disease-related causes; DOOD, died of other disease; WBC, white blood cell; PB, peripheral blood; TKI, tyrosine kinase inhibitor; BP, blast phase.
Twelve patients were initially on 400 mg/day of imatinib, one patients on 300, six patients on 600, and 23 on 800 mg/day (including five patients also taking pegylated interferon and recombinant granulocyte-macrophage colony-stimulating factor, usually for short duration); nine of these patients had subsequent dose reductions due to toxicities, five patients had dose increases due to persistent BCR-ABL1 transcript levels.
Six of seven patients were initially on 400 mg/day; one patient on 800, with dose limiting toxicities precluding dose escalation in five patients.
Twelve patients were initially on 300 to 500 mg/day of imatinib (most on 400 mg), seven patients were on 800 mg per day (including three taking pegylated-intron/sargramostim). In eight patients, dose escalation was attempted, in the remaining there were dose-limiting toxicities. Two patients with resistant disease at the 1 year had transient responses in the first 3 to 6 months of treatment.
Four patients developed secondary imatinib resistance (with 1 BP, 1 AP, 2 CP) at a median of 24 months after initial therapy, with two switched to a new TKI.
Three patients developed secondary imatinib resistance (2 AP, 1 CP) and were switched to a new TKI (2 dasatinib, 1 bosutinib) at 22, 24, and 33 months post-imatinib start, three patients were continued on imatinib, and one patient was lost to follow-up.
Eleven patients were switched to a new TKI (dasatinib in three, bosutinib in seven, and nilotinib in one) after a mean duration of imatinib of 16.9 months (range, 6 to 42.7 months), three had stem cell transplant, and five had dose escalation with imatinib. Two patients with resistant disease died before 1 year; two were lost to follow-up.
One optimal response and two resistant patients could not be scored.