| Autor: |
Mueller, Ina, Ehlert, Karoline, Endres, Stefanie, Pill, Lena, Siebert, Nikolai, Kietz, Silke, Brock, Penelope, Garaventa, Alberto, Valteau-Couanet, Dominique, Janzek, Evelyne, Hosten, Norbert, Zinke, Andreas, Barthlen, Winfried, Varol, Emine, Loibner, Hans, Ladenstein, Ruth, Lode, Holger N. |
| Zdroj: |
mAbs; January 2018, Vol. 10 Issue: 1 p55-61, 7p |
| Abstrakt: |
ABSTRACTImmunotherapy with short term infusion (STI) of monoclonal anti-GD2antibody (mAb) ch14.18 (4 × 25 mg/m2/d; 8–20 h) in combination with cytokines and 13-cis retinoic acid (RA) prolonged survival in high-risk neuroblastoma (NB) patients. Here, we investigated long-term infusion (LTI) of ch14.18 produced in Chinese hamster ovary cells (ch14.18/CHO; 10 × 10 mg/m2; 24 h) in combination with subcutaneous (s.c.) interleukin-2 (IL-2) in a single center program and report clinical response, toxicity and survival. Fifty-three high-risk NB patients received up to 6 cycles of 100 mg/m2ch14.18/CHO (d8–17) as LTI combined with 6 × 106IU/m2s.c. IL-2 (d1–5; 8–12) and 160 mg/m2oral RA (d19–32). Pain toxicity was documented with validated pain scores and intravenous (i.v.) morphine usage. Response was assessed in 37/53 evaluable patients following International Neuroblastoma Risk Group criteria. Progression-free (PFS) and overall survival (OS) was analyzed by the Kaplan-Meier method and compared to a matched historical control group from the database of AIEOP, the “Italian Pediatric Ematology and Oncology Association”. LTI of ch14.18/CHO showed acceptable toxicity profile indicated by low pain scores, reduced i.v. morphine usage and low frequency of Grade ≥3 adverse events that allowed outpatient treatment. We observed a best response rate of 40.5% (15/37; 5 CR, 10 PR), 4-year (4 y) PFS of 33.1% (observation 0.1- 4.9 y, mean: 2.2 y) and a 4 y OS of 47.7% (observation 0.27 – 5.20 y, mean: 3.6 y). Survival of the entire cohort (53/53) and the relapsed patients (29/53) was significantly improved compared to historical controls. LTI of ch14.18/CHO thus shows an acceptable toxicity profile, objective clinical responses and a strong signal of clinical efficacy in NB patients. |
| Databáze: |
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