TY - JOUR
T1 - Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH?
AU - Schouwenburg, Maartje G.
AU - Suijkerbuijk, Karijn P. M.
AU - Koornstra, Rutger H. T.
AU - Jochems, Anouk
AU - van Zeijl, Michiel C. T.
AU - van den Eertwegh, Alfons J. M.
AU - Haanen, John B. A. G.
AU - Aarts, Maureen J. B.
AU - van Akkooi, Alexander C. J.
AU - van den Berkmortel, Franchette W. P. J.
AU - de Groot, Jan Willem B.
AU - Hospers, Geke A. P.
AU - Kapiteijn, Ellen
AU - Kruit, Wim H.
AU - Piersma, Djura
AU - van Rijn, Rozemarijn S.
AU - ten Tije, Albert J.
AU - Vreugdenhil, Gerard
AU - van der Hoeven, Jacobus J. M.
AU - Wouters, Michel W. J. M.
N1 - Funding Information:
Funding: This research was funded by The Netherlands Organization for Health Research and Development (ZonMW), grant number 836002002. This subsidy is part of the program of effectiveness research of high-cost medicine. The first four years (2012–2016) of the Dutch Melanoma Treatment Registry (DMTR) were sponsored by Roche Nederland B.V, Bristol-Myers Squibb (BMS), GlaxoSmithKline (GSK)/Novartis and, since 2015, also by Merck Sharp & Dohme (MSD).
Funding Information:
This research was funded by The Netherlands Organization for Health Research and Development (ZonMW), grant number 836002002. This subsidy is part of the program of effectiveness research of high-cost medicine. The first four years (2012?2016) of the Dutch Melanoma Treatment Registry (DMTR) were sponsored by Roche Nederland B.V, Bristol-Myers Squibb (BMS), GlaxoSmithKline (GSK)/Novartis and, since 2015, also by Merck Sharp & Dohme (MSD).
Funding Information:
Conflicts of Interest: K.S. has consulting/advisory relationships with BMS and MSD. She received honoraria from Novartis, Pierre Fabre, and Roche. A.A. has consulting/advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, MSD, and Merck-Pfizer. He received research funding from Amgen and Novartis. He received travel, accommodations, and expenses from Amgen and Novartis. J.G. has advisory relationships with BMS, MSD, and Roche. G.H. has consulting/advisory relationships with Roche, MSD, BMS, and Novartis. Her institution received research funding from BMS. J.H. provided consultation, attended advisory boards, and/or provided lectures for MSD, BMS, Roche, and Novartis, for which NKI received honoraria. His institution received grant support from BMS and Novartis. A.E. has consulting/advisory relationships with BMS, Roche, MSD, and Novartis. He received a study grant from Roche. R. K. has received speaker fees from BMS, MSD, and Roche. He has advisory relationships with BMS, MSD, Novartis, and Roche. He received research grants from BMS and Roche. E. K. has advisory relationships with BMS, Novartis, Roche, Merck, Amgen, Pierre-Fabre, EISAI, Bayer, and Genzyme-Sanofi (all paid to institution). She received research grants from BMS. The other authors report no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/12
Y1 - 2019/12
N2 - The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (>= 2x upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4-5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.
AB - The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (>= 2x upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4-5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.
KW - melanoma
KW - metastasis
KW - targeted therapy
KW - immune checkpoint inhibitors
KW - lactate dehydrogenase
KW - real-life data
KW - prognostic factors
KW - METASTATIC MELANOMA
KW - LACTATE-DEHYDROGENASE
KW - IPILIMUMAB
KW - DABRAFENIB
KW - PEMBROLIZUMAB
KW - NIVOLUMAB
KW - OUTCOMES
U2 - 10.3390/cancers11121940
DO - 10.3390/cancers11121940
M3 - Article
C2 - 31817189
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 12
M1 - 1940
ER -