Cytokine release syndrome (CRS) in patients treated with NY-ESO-1^c259 TCR.

Abstract

3040 Background: Cytokine release syndrome (CRS) is observed with adoptive T-cell therapies (ACT) with varying frequency. CRS can be life threatening and may require steroids, which hinder the effectiveness of ACT. CRS prevalence and severity within the context NY-ESO-1C259T across 5 studies in 4 tumor types were examined: synovial sarcoma (SS), ovarian cancer (OC), myeloma and melanoma. Methods: A review of CRS including evaluation of concurrent AEs and reported symptoms, cytokine levels and CRP was performed in pts treated with NY-ESO-1C259T. AEs that are known manifestations of CRS were summarized for each pt. diagnosed with CRS. CRP was measured by the hospital laboratory. Serum cytokines were measured by Luminex. Results: Of 53 pts treated with NY-ESO-1C259T, 7 were diagnosed with CRS (Table). 2/7 pts received immunomodulatory treatment for mitigation of CRS: methylprednisolone 2 mg/kg x 2 doses with prednisone taper (n=1, G3) and Tocilizumab 4 mg/kg x 1 dose (n=1 G4). Diagnosis of CRS was made within the first 2 wks in all 7 pts and resolved within 32 days after the T-cell infusions. Onset of CRS coincided with T-cell expansion. Elevated IL-6 and IL-8 were observed during CRS. Timing of the increase of IL-6 and IL-8 suggests involvement in the effector phase of CRS instead of its induction. IL-5, IL-15, INF-γ and GM-CSF showed no discernable pattern associated with CRS. Conclusions: CRS was observed in 13% of pts treated with NY-ESO-1C259T. Symptoms manifest in the first 2 wks and have been effectively managed with supportive care measures. Two pts required immunomodulatory therapy. While there are differences in the pt. populations, incidence of CRS with NY-ESO-1C259T appears to be of lower frequency and severity than reported with CD19 CAR-T therapy. Data summary. Trial/Patient SS 205 SS 207 SS 208 SS 261 SS 264 OC 101 OC 203 Grade CRS/duration (days) 2/3 1/8 3/24 3/11 4/11 3/10 2/7 Responder Y N Y N Y N × Fever/Rash/Diarrhea Y/Y/Y Y/NR/Y Y/Y/Y Y/NR/Y Y/Y/NR Y/Y/Y Y/Y/NR CNS symptoms NR Y Y NR NR Y Y Dyspnea/hypoxia NR NR NR Y Y Y NR Hypotension Y NR NR NR Y Y Y Fatigue N N Y Y NR Y NR CRP (mg/L) 261 157 198 175 182 ND 143 IL-6 peak/IL-8 (pg/mL) 385/129 114/671 72/226 ND 987/394 80/150 ND × too early to assess response; NR – not reported; ND – not done