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Inflammatory response and treatment tolerance of long‐term infusion of the anti‐GD 2 antibody ch14.18/CHO in combination with interleukin‐2 in patients with high‐risk neuroblastoma
Author(s) -
Ceylan Kiraz,
Jahns Luciana J.,
Lode Bjoern N.,
Ehlert Karoline,
Kietz Silke,
TroschkeMeurer Sascha,
Siebert Nikolai,
Lode Holger N.
Publication year - 2018
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26967
Subject(s) - medicine , gastroenterology
Background The monoclonal anti‐GD 2 antibody ch14.18/CHO in combination with IL‐2 is active and effective in high‐risk neuroblastoma (NB) patients. Here, we investigated the inflammatory response and treatment tolerance of long‐term infusion (LTI) of ch14.18/CHO (10 × 10 mg/m 2 ; 24 hr) in combination with subcutaneous (s.c.) IL‐2 in a single center program. Methods Fifty‐three NB patients received up to six cycles of 100 mg/m 2 ch14.18/CHO (d8–18, where d represents day(s)) as LTI combined with 6 × 10 6 IU/m 2 s.c. IL‐2 (d1–5; 8–12) and 160 mg/m 2 oral 13‐cis retinoic acid (RA) (d19–32). Side effects of ch14.18/CHO and IL‐2 treatment require hospitalization of patients on d8. Treatment tolerance was evaluated daily with clinical parameters (body temperature, vital signs, Lansky performance status, requirement of i.v. concomitant medication) to define an outpatient candidate status. sIL‐2‐R and C‐reactive protein values were determined to assess the inflammatory response. Results LTI of ch14.18/CHO (d8–18) in combination with s.c.IL‐2 (d8–12) showed an acceptable treatment tolerance that allowed all patients to receive part of the treatment as an outpatient (median time point of discharge: d15 for all cycles). The treatment tolerance improved from cycle to cycle and the time to become an outpatient candidate decreased from d15 to d13 in subsequent cycles. Clinical and laboratory parameters indicate a maximum inflammatory response at d11 of each cycle. Interestingly, the soluble IL‐2 receptor remained increased at baseline of the next cycle indicating immune activation over the entire treatment period of 6 months. Conclusions LTI of ch14.18/CHO combined with s.c.IL‐2 shows an improved tolerance in subsequent cycles allowing outpatient treatment.