Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy

Osama Mohamad, Alberto Diaz de Leon, Samuel Schroeder, Andrew Leiker, Alana Christie, Elizabeth Zhang-Velten, Lakshya Trivedi, Saad Khan, Neil B. Desai, Aaron Laine, Kevin Albuquerque, Puneeth Iyengar, Yull Arriaga, Kevin Courtney, David E. Gerber, Hans Hammers, Hak Choy, Robert Timmerman, James Brugarolas, Raquibul Hannan

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Integration of hypofractionated body radiotherapy (H-RT) into immune checkpoint inhibitor (ICI) therapy may be a promising strategy to improve the outcomes of ICIs, although sufficient data is lacking regarding the safety and efficacy of this regimen. We, hereby, reviewed the safety and efficacy of this combination in 59 patients treated with H-RT during or within 8 weeks of ICI infusion and compared results with historical reports of ICI treatment alone. Most patients had RCC or melanoma. Median follow-up was 11 months. Most patients received either Nivolumab alone or with Ipilimumab; 83% received stereotactic RT and 17% received conformal H-RT. Any grade adverse events (AEs) were reported in 46 patients, and grade 3–4 in 12 patients without any treatment-related grade 5 toxicity. The most common grade 3 AEs were fatigue and pneumonitis. Grade 3–4 toxicities were higher with ICI combination and with simultaneous ICIs. Overall, most any-grade or grade ≥3 AE rates did not differ significantly from historically reported rates with single-agent or multi-agent ICIs. Toxicity did not correlate with H-RT site, dose, fraction number, tumor type, or ICI and H-RT sequencing. Median progression-free survival was 6.5 months. Objective response rate (ORR) was 26%; 10% had complete response (CR). Median duration of response was 9.4 ± 4.6 months. H-RT of lung lesions was more likely to achieve CR than other sites. H-RT of bone lesions had a lower ORR than non-bone H-RT. In conclusion, combining body H-RT with ICIs is safe and promising. Prospective validation is warranted.

Original languageEnglish (US)
JournalOncoImmunology
DOIs
StateAccepted/In press - Mar 10 2018

Fingerprint

Radiotherapy
Safety
Disease-Free Survival
Fatigue
Melanoma
Pneumonia
Therapeutics
Bone and Bones
Lung
Neoplasms

Keywords

  • hypofractionation
  • immune checkpoint inhibitors
  • Immunotherapy
  • Ipilimumab
  • Nivolumab
  • radiation
  • radiotherapy
  • stereotactic radiation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

@article{1191050d4644472db994162ff5f81a04,
title = "Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy",
abstract = "Integration of hypofractionated body radiotherapy (H-RT) into immune checkpoint inhibitor (ICI) therapy may be a promising strategy to improve the outcomes of ICIs, although sufficient data is lacking regarding the safety and efficacy of this regimen. We, hereby, reviewed the safety and efficacy of this combination in 59 patients treated with H-RT during or within 8 weeks of ICI infusion and compared results with historical reports of ICI treatment alone. Most patients had RCC or melanoma. Median follow-up was 11 months. Most patients received either Nivolumab alone or with Ipilimumab; 83{\%} received stereotactic RT and 17{\%} received conformal H-RT. Any grade adverse events (AEs) were reported in 46 patients, and grade 3–4 in 12 patients without any treatment-related grade 5 toxicity. The most common grade 3 AEs were fatigue and pneumonitis. Grade 3–4 toxicities were higher with ICI combination and with simultaneous ICIs. Overall, most any-grade or grade ≥3 AE rates did not differ significantly from historically reported rates with single-agent or multi-agent ICIs. Toxicity did not correlate with H-RT site, dose, fraction number, tumor type, or ICI and H-RT sequencing. Median progression-free survival was 6.5 months. Objective response rate (ORR) was 26{\%}; 10{\%} had complete response (CR). Median duration of response was 9.4 ± 4.6 months. H-RT of lung lesions was more likely to achieve CR than other sites. H-RT of bone lesions had a lower ORR than non-bone H-RT. In conclusion, combining body H-RT with ICIs is safe and promising. Prospective validation is warranted.",
keywords = "hypofractionation, immune checkpoint inhibitors, Immunotherapy, Ipilimumab, Nivolumab, radiation, radiotherapy, stereotactic radiation",
author = "Osama Mohamad and {Diaz de Leon}, Alberto and Samuel Schroeder and Andrew Leiker and Alana Christie and Elizabeth Zhang-Velten and Lakshya Trivedi and Saad Khan and Desai, {Neil B.} and Aaron Laine and Kevin Albuquerque and Puneeth Iyengar and Yull Arriaga and Kevin Courtney and Gerber, {David E.} and Hans Hammers and Hak Choy and Robert Timmerman and James Brugarolas and Raquibul Hannan",
year = "2018",
month = "3",
day = "10",
doi = "10.1080/2162402X.2018.1440168",
language = "English (US)",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",

}

TY - JOUR

T1 - Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy

AU - Mohamad, Osama

AU - Diaz de Leon, Alberto

AU - Schroeder, Samuel

AU - Leiker, Andrew

AU - Christie, Alana

AU - Zhang-Velten, Elizabeth

AU - Trivedi, Lakshya

AU - Khan, Saad

AU - Desai, Neil B.

AU - Laine, Aaron

AU - Albuquerque, Kevin

AU - Iyengar, Puneeth

AU - Arriaga, Yull

AU - Courtney, Kevin

AU - Gerber, David E.

AU - Hammers, Hans

AU - Choy, Hak

AU - Timmerman, Robert

AU - Brugarolas, James

AU - Hannan, Raquibul

PY - 2018/3/10

Y1 - 2018/3/10

N2 - Integration of hypofractionated body radiotherapy (H-RT) into immune checkpoint inhibitor (ICI) therapy may be a promising strategy to improve the outcomes of ICIs, although sufficient data is lacking regarding the safety and efficacy of this regimen. We, hereby, reviewed the safety and efficacy of this combination in 59 patients treated with H-RT during or within 8 weeks of ICI infusion and compared results with historical reports of ICI treatment alone. Most patients had RCC or melanoma. Median follow-up was 11 months. Most patients received either Nivolumab alone or with Ipilimumab; 83% received stereotactic RT and 17% received conformal H-RT. Any grade adverse events (AEs) were reported in 46 patients, and grade 3–4 in 12 patients without any treatment-related grade 5 toxicity. The most common grade 3 AEs were fatigue and pneumonitis. Grade 3–4 toxicities were higher with ICI combination and with simultaneous ICIs. Overall, most any-grade or grade ≥3 AE rates did not differ significantly from historically reported rates with single-agent or multi-agent ICIs. Toxicity did not correlate with H-RT site, dose, fraction number, tumor type, or ICI and H-RT sequencing. Median progression-free survival was 6.5 months. Objective response rate (ORR) was 26%; 10% had complete response (CR). Median duration of response was 9.4 ± 4.6 months. H-RT of lung lesions was more likely to achieve CR than other sites. H-RT of bone lesions had a lower ORR than non-bone H-RT. In conclusion, combining body H-RT with ICIs is safe and promising. Prospective validation is warranted.

AB - Integration of hypofractionated body radiotherapy (H-RT) into immune checkpoint inhibitor (ICI) therapy may be a promising strategy to improve the outcomes of ICIs, although sufficient data is lacking regarding the safety and efficacy of this regimen. We, hereby, reviewed the safety and efficacy of this combination in 59 patients treated with H-RT during or within 8 weeks of ICI infusion and compared results with historical reports of ICI treatment alone. Most patients had RCC or melanoma. Median follow-up was 11 months. Most patients received either Nivolumab alone or with Ipilimumab; 83% received stereotactic RT and 17% received conformal H-RT. Any grade adverse events (AEs) were reported in 46 patients, and grade 3–4 in 12 patients without any treatment-related grade 5 toxicity. The most common grade 3 AEs were fatigue and pneumonitis. Grade 3–4 toxicities were higher with ICI combination and with simultaneous ICIs. Overall, most any-grade or grade ≥3 AE rates did not differ significantly from historically reported rates with single-agent or multi-agent ICIs. Toxicity did not correlate with H-RT site, dose, fraction number, tumor type, or ICI and H-RT sequencing. Median progression-free survival was 6.5 months. Objective response rate (ORR) was 26%; 10% had complete response (CR). Median duration of response was 9.4 ± 4.6 months. H-RT of lung lesions was more likely to achieve CR than other sites. H-RT of bone lesions had a lower ORR than non-bone H-RT. In conclusion, combining body H-RT with ICIs is safe and promising. Prospective validation is warranted.

KW - hypofractionation

KW - immune checkpoint inhibitors

KW - Immunotherapy

KW - Ipilimumab

KW - Nivolumab

KW - radiation

KW - radiotherapy

KW - stereotactic radiation

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U2 - 10.1080/2162402X.2018.1440168

DO - 10.1080/2162402X.2018.1440168

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SN - 2162-4011

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