Table 3.
Organ damage in patients with advanced SM: eligibility and response criteria for CI
| Organ damage | Organ damage eligible for CI response | CI response criteria |
|---|---|---|
| Nonhematologic | ||
| Ascites or pleural effusions | (1) Symptomatic ascites or pleural effusion requiring medical intervention such as use of diuretics (grade 2), OR (2) ≥ 2 therapeutic paracenteses or thoracenteses at least 28 d apart over 12 wk prior to study entry (grade 3), and one of the procedures is performed during the 6 wk prior to drug start | (1) Complete resolution of symptomatic ascites or pleural effusion* AND no longer in need of diuretic(s) for ≥ 12 wk, OR (2) No therapeutic paracentesis or thoracentesis for ≥ 12 wk |
| Liver function abnormalities | ≥ Grade 2 abnormalities in direct bilirubin, AST, ALT, or AP† in the presence of ascites, and/or clinically-relevant portal hypertension, and/or liver MC infiltration that is biopsy-proven or other causes for abnormal liver function are not identified | Reversion of 1 or more liver function tests to normal range for ≥ 12 wk |
| Hypoalbuminemia | ≥ Grade 2 hypoalbuminemia (< 3.0 g/dL) | Reversion of albumin to normal range for ≥ 12 wk |
| Symptomatic marked splenomegaly | Symptomatic marked splenomegaly: a spleen that is palpable > 5 cm below the left costal margin and the patient endorses symptoms of discomfort and /or early satiety | ≥ 50% reduction in palpable splenomegaly and no endorsement of discomfort and/or early satiety for ≥ 12 wk (3D computed tomography/magnetic resonance imaging evaluation may also be undertaken.) |
| Hematologic | ||
| ANC | Baseline grade ≥ 3 ANC (< 1 × 109/L) | A minimum 100% increase in the ANC and an ANC of at least 0.5 × 109/L for ≥ 12 wk |
| Anemia (transfusion-independent) | Grade ≥ 2 anemia (Hb < 10 g/dL) | An increase in Hb level of at least 2 g/dL that is maintained for ≥ 12 wk |
| Anemia (transfusion-dependent) | Transfusion of a minimum of 6 units of PRBC in the 12 wk before the start of treatment with the most recent transfusion occurring in the previous 4 wk. RBC transfusions are only considered as part of the baseline criteria if they are administered for an Hb level ≤ 8.5 g/dL and not associated with bleeding, hemolysis, or therapy | Transfusion independence for ≥ 12 wk and maintenance of a minimal Hb level of 8.5 g/dL at the end of the 12 wk period of response duration |
| Thrombocytopenia (transfusion-independent) | Grade ≥ 2 thrombocytopenia (< 75 × 109/L) | A minimum 100% increase in the platelet count and an absolute platelet count increase of at least 50 × 109/L and no need for platelet transfusions for ≥ 12 wk |
| Thrombocytopenia (transfusion-dependent) | 1) Transfusion of a minimum of 6 units of apheresed platelets during the 12 wk preceding treatment; and 2) at least 2 units transfused in the previous 4 wk; and 3) transfusions are administered only for a platelet count < 20 × 109/L | Transfusion-independence for a minimal period of 12 wk and maintenance of a platelet count of ≥ 20 × 109/L |
The response criteria were determined using National Institutes of Health CTC version 4.03.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; PRBC, packed red blood cells.
Radiologic use of the term trace or minimal for ascites or pleural effusion indicates a substantial improvement of pretreatment pathologic fluid accumulation, which required medical intervention. These terms are acceptable in the absence of the radiologists' use of the term(s) complete disappearance or resolution to describe the change in ascites or effusion.
Gamma-glutamyl transferase can be used to determine the liver vs bone origin of alkaline phosphatase but is not considered eligible as a liver-related organ damage laboratory abnormality. The grades and associated laboratory ranges above the upper limit of normal used for the total bilirubin according to CTC version 4.03 should be applied to the direct bilirubin.