Table 1.
IL-15 agent | MTD or expansion dose/dosing schedule | Study population | Serious and notable adverse events | Maximum fold increase in total NK cells at MTD | Maximum fold increase in CD56 bright NK cells | Maximum fold increase in CD8 T cells | Best clinical Response | References |
---|---|---|---|---|---|---|---|---|
E. coli rhIL-15 | 0.3 μg/kg/d bolus i.v. 12 consecutive days | 18 patients with malignant melanoma or renal cell cancer | Grade 3 hypotension Grade 3 thrombocytopenia Grade 3 ALT, AST elevations | 2–3 | 3–4 | 3 | Stable disease (5 patients had 10–30% decrease in marker lesions and 2 disappearance of lung lesions) | Conlon et al. (43) National Cancer Institute, NIH |
E. coli rhIL-15 | 2 μg/kg/d CIV for 10 days | 27 patients with metastatic solid tumors | 2 deaths (one due to gastrointestinal ischemia and one due to disease progression) Grade 3 bleeding Grade 3 papilledema Grade 3 uveitis Grade 3 hepatic encephalopathy | 38 | 358 | 5.8 | Stable disease | Conlon et al. (45) National Cancer Institute, NIH |
E. coli rhIL-15 | 2 μg/kg/d SC days 1–5, 8–12 | 19 patients with advanced solid tumors | Grade 2 pancreatitis Grade 3 cardiac/chest pain | 10.8 | 39.7 | 3.3 | Stable disease | Miller et al. (44) Minnesota Cancer Center |
ALT-803 | 10 μg/kg IV or SC weekly for 4 weeks | 33 patients with hematological malignancies | 2 deaths (one due to sepsis, one due to intracranial hemorrhage) Grade 4 sepsis Grade 2 pemphigus | 8 | 8 | 2 | 1 CR, 1 PR, 3 SD | Romee et al. (46) Minnesota Cancer Center |
ALT-803 | 20 μg/kg SC 4 consecutive weeks every 6 weeks | 21 patients 11 IV, 13 SC with solid tumors | Grade 4 congestive heart failure Grade 4 neutropenia Injection site reaction | 3.3 | 6.3 | 6.3 | No PR or CR | Margolin et al. (47) Fred Hutchinson Cancer Center |
CIV, continuous intravenous infusion; d, day; IL-15, interleukin 15; IV, intravenous; Kg, kilogram; NA, not available; SC, subcutaneous; CR, complete response; PR, partial response; SD, stable disease; CRS, cytokine release syndrome.