TY - JOUR
T1 - Association of Anti-TNF with Decreased Survival in Steroid Refractory Ipilimumab and Anti-PD1-Treated Patients in the Dutch Melanoma Treatment Registry
AU - Verheijden, Rik J.
AU - May, Anne M.
AU - Blank, Christian U.
AU - Aarts, Maureen J. B.
AU - van den Berkmortel, Franchette W. P. J.
AU - van den Eertwegh, Alfonsus J. M.
AU - de Groot, Jan Willem B.
AU - Boers-Sonderen, Marye J.
AU - van der Hoeven, Jacobus J. M.
AU - Hospers, Geke A.
AU - Piersma, Djura
AU - van Rijn, Rozemarijn S.
AU - ten Tije, Albert J.
AU - van der Veldt, Astrid A. M.
AU - Vreugdenhil, Gerard
AU - van Zeijl, Michiel C. T.
AU - Wouters, Michel W. J. M.
AU - Haanen, John B. A. G.
AU - Kapiteijn, Ellen
AU - Suijkerbuijk, Karijn P. M.
N1 - Funding Information:
R.J. Verheijden is a medical student participating in the Honours programme of the Faculty of Medicine, UMC Utrecht. This specific research manuscript received no external funding. The Netherlands Organization for Health Research and Development funded the start-up of the Dutch Melanoma Treatment Registry (DMTR). Grant number: 836002002. This grant was awarded under the effectiveness research for high-cost medicine programme. From its foundation, the DMTR has been sponsored by BMS, Novartis, Roche Nederland B.V., MSD, and Pierre Fabre via the Dutch Institute for Clinical Auditing (DICA).
Publisher Copyright:
© 2020 American Association for Cancer Research Inc.. All rights reserved.
PY - 2020/5
Y1 - 2020/5
N2 - Purpose: Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival is largely unknown.Experimental Design: Using data from the prospective nation-wide Dutch Melanoma Treatment Registry (DMTR), we analyzed the association between severe toxicity and overall survival (OS) in 1,250 patients with advanced melanoma who were treated with immune checkpoint inhibitors (ICI) in first line between 2012 and 2017. Furthermore, we analyzed whether toxicity management affected survival in these patients.Results: A total of 1,250 patients were included, of whom 589 received anti-PD1 monotherapy, 576 ipilimumab, and 85 combination therapy. A total of 312 patients (25%) developed severe (grade >= 3) toxicity. Patients experiencing severe ICI toxicity had a significantly prolonged survival with a median OS of 23 months compared with 15 months for patients without severe toxicity [hazard ratio (HRadj) = 0.77; 95% confidence interval (CI), 0.63-0.93]. Among patients experiencing severe toxicity, survival was significantly decreased in patients who received anti-TNF +/- steroids for steroid-refractory toxicity compared with patients whoweremanaged with steroids only (HRadj = 1.61; 95% CI, 1.03-2.51), with a median OS of 17 and 27 months, respectively.Conclusions: Patients experiencing severe ICI toxicity have a prolonged OS. However, this survival advantage is abrogated when anti- TNF is administered for steroid-refractory toxicity. Further prospective studies are needed to assess the effect of different immunosuppressive regimens on checkpoint inhibitor efficacy.
AB - Purpose: Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival is largely unknown.Experimental Design: Using data from the prospective nation-wide Dutch Melanoma Treatment Registry (DMTR), we analyzed the association between severe toxicity and overall survival (OS) in 1,250 patients with advanced melanoma who were treated with immune checkpoint inhibitors (ICI) in first line between 2012 and 2017. Furthermore, we analyzed whether toxicity management affected survival in these patients.Results: A total of 1,250 patients were included, of whom 589 received anti-PD1 monotherapy, 576 ipilimumab, and 85 combination therapy. A total of 312 patients (25%) developed severe (grade >= 3) toxicity. Patients experiencing severe ICI toxicity had a significantly prolonged survival with a median OS of 23 months compared with 15 months for patients without severe toxicity [hazard ratio (HRadj) = 0.77; 95% confidence interval (CI), 0.63-0.93]. Among patients experiencing severe toxicity, survival was significantly decreased in patients who received anti-TNF +/- steroids for steroid-refractory toxicity compared with patients whoweremanaged with steroids only (HRadj = 1.61; 95% CI, 1.03-2.51), with a median OS of 17 and 27 months, respectively.Conclusions: Patients experiencing severe ICI toxicity have a prolonged OS. However, this survival advantage is abrogated when anti- TNF is administered for steroid-refractory toxicity. Further prospective studies are needed to assess the effect of different immunosuppressive regimens on checkpoint inhibitor efficacy.
KW - ADVERSE EVENTS
KW - METASTATIC MELANOMA
KW - COMBINED NIVOLUMAB
KW - IMMUNE
KW - CANCER
KW - MONOTHERAPY
KW - EFFICACY
KW - SAFETY
U2 - 10.1158/1078-0432.ccr-19-3322
DO - 10.1158/1078-0432.ccr-19-3322
M3 - Article
C2 - 31988197
SN - 1078-0432
VL - 26
SP - 2268
EP - 2274
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -