Details

Autor(en) / Beteiligte

• Tang, Chad
• Welsh, James W
• de Groot, Patricia
• Massarelli, Erminia
• Chang, Joe Y
• Hess, Kenneth R
• Basu, Sreyashi
• Curran, Michael A
• Cabanillas, Maria E
• Subbiah, Vivek
• Fu, Siqing
• Tsimberidou, Apostolia M
• Karp, Daniel
• Gomez, Daniel R
• Diab, Adi
• Komaki, Ritsuko
• Heymach, John V
• Sharma, Padmanee
• Naing, Aung
• Hong, David S

Titel

Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells

Ist Teil von

• Clinical cancer research, 2017-03, Vol.23 (6), p.1388-1396

Ort / Verlag

United States: American Association for Cancer Research Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Little prospective data are available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiotherapy (SABR) with ipilimumab. SABR was given either concurrently (1 day after the first dose) or sequentially (1 week after the second dose) with ipilimumab (3 mg/kg every 3 weeks for 4 doses) to five treatment groups: concurrent 50 Gy (in 4 fractions) to liver; sequential 50 Gy (in 4 fractions) to liver; concurrent 50 Gy (in 4 fractions) to lung; sequential 50 Gy (in 4 fractions) to lung; and sequential 60 Gy (in 10 fractions) to lung or liver. MTD was determined with a 3 + 3 dose de-escalation design. Immune marker expression was assessed by flow cytometry. Among 35 patients who initiated ipilimumab, 2 experienced dose-limiting toxicity and 12 (34%) grade 3 toxicity. Response outside the radiation field was assessable in 31 patients. Three patients (10%) exhibited partial response and 7 (23%) experienced clinical benefit (defined as partial response or stable disease lasting ≥6 months). Clinical benefit was associated with increases in peripheral CD8 T cells, CD8 /CD4 T-cell ratio, and proportion of CD8 T cells expressing 4-1BB and PD1. Liver (vs. lung) irradiation produced greater T-cell activation, reflected as increases in the proportions of peripheral T cells expressing ICOS, GITR, and 4-1BB. Combining SABR and ipilimumab was safe with signs of efficacy, peripheral T-cell markers may predict clinical benefit, and systemic immune activation was greater after liver irradiation. .