PMID- 37142875
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20230717
IS  - 1179-1888 (Electronic)
IS  - 1175-0561 (Print)
IS  - 1175-0561 (Linking)
VI  - 24
IP  - 3
DP  - 2023 May
TI  - Features and Long-Term Outcomes of Stage IV Melanoma Patients Achieving Complete 
      Response Under Anti-PD-1-Based Immunotherapy.
PG  - 453-467
LID - 10.1007/s40257-023-00775-7 [doi]
AB  - BACKGROUND: Immune checkpoint inhibition (ICI) has changed the melanoma treatment 
      spectrum. Few studies have examined the characteristics and long-term outcomes of 
      patients achieving complete response (CR) under ICI. MATERIALS AND METHODS: We 
      evaluated patients with unresectable stage IV melanoma treated with first-line 
      ICI. The characteristics of those achieving CR were compared with those not 
      achieving CR. Progression-free survival (PFS) and overall survival (OS) were 
      assessed. Late-onset toxicities, response to second-line treatment, the 
      prognostic value of clinicopathologic features, and blood markers were examined. 
      RESULTS: A total of 265 patients were included; 41 (15.5%) achieved CR, while 224 
      (84.5%) had progressive disease, stable disease, or partial response. At the 
      therapy start, those who had CR were more likely to be older than 65 years of age 
      (p = 0.013), have a platelet-to-lymphocyte ratio below 213 (p = 0.036), and have 
      lower lactate dehydrogenase levels (p = 0.008) than those not achieving a CR. For 
      those who discontinued therapy after CR, the median follow-up time after CR was 
      56 months (interquartile range [IQR] 52-58) and the median time from CR to 
      therapy end was 10 months (IQR 1-17). Five-year PFS after CR was 79% and 5-year 
      OS was 83%. Most complete responders had a normalization of S100 at the time of 
      CR (p < 0.001). In simple Cox regression analysis, age below 77 years at CR 
      (p = 0.04) was associated with better prognosis after CR. Eight patients received 
      second-line ICI; disease control was seen in 63%. Late immune-related toxicities 
      occurred in 25% of patients, most being cutaneous immune-related toxicities. 
      CONCLUSIONS: Response, according to the Response Evaluation Criteria in Solid 
      Tumors (RECIST) criteria, is, until now, the most important prognostic factor, 
      and CR is a valid surrogate marker for long-term survival in patients treated 
      with ICI. Our results highlight the importance of investigating the optimal 
      therapy duration in complete responders.
CI  - (c) 2023. The Author(s).
FAU - Chatziioannou, Eftychia
AU  - Chatziioannou E
AUID- ORCID: 0000-0002-7843-7160
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Leiter, Ulrike
AU  - Leiter U
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Thomas, Ioannis
AU  - Thomas I
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Keim, Ulrike
AU  - Keim U
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Seeber, Olivia
AU  - Seeber O
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Meiwes, Andreas
AU  - Meiwes A
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Boessenecker, Isabell
AU  - Boessenecker I
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Gonzalez, Stephanie Sanchez
AU  - Gonzalez SS
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Torres, Francisco Merraz
AU  - Torres FM
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Niessner, Heike
AU  - Niessner H
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
AD  - Cluster of Excellence iFIT (EXC 2180), Tuebingen, Germany.
FAU - Sinnberg, Tobias
AU  - Sinnberg T
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
AD  - Cluster of Excellence iFIT (EXC 2180), Tuebingen, Germany.
AD  - Department of Dermatology, Venereology and Allergology, 
      Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Forschner, Andrea
AU  - Forschner A
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
FAU - Flatz, Lukas
AU  - Flatz L
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
AD  - Institute for Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Amaral, Teresa
AU  - Amaral T
AUID- ORCID: 0000-0002-2516-5181
AD  - Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University 
      of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany. 
      teresa.amaral@med.uni-tuebingen.de.
AD  - Cluster of Excellence iFIT (EXC 2180), Tuebingen, Germany. 
      teresa.amaral@med.uni-tuebingen.de.
LA  - eng
PT  - Journal Article
DEP - 20230504
PL  - New Zealand
TA  - Am J Clin Dermatol
JT  - American journal of clinical dermatology
JID - 100895290
SB  - IM
MH  - Humans
MH  - Aged
MH  - *Melanoma
MH  - Prognosis
MH  - Remission Induction
MH  - Progression-Free Survival
MH  - Immunotherapy
MH  - Retrospective Studies
PMC - PMC10195722
COIS- Ulrike Leiter reports research support from MSD; consulting fees and honoraria 
      from Sun Pharma, Sanofi (personal and institutional), MSD (personal and 
      institutional), Novartis, Roche, and Almirall Hermal; support for attending 
      meetings from Sun Pharma; and participation on a Data Safety Monitoring Board or 
      Advisory Board from Sun Pharma, Sanofi, MSD, Novartis, Roche, and Almirall 
      Hermal, outside the submitted work. Ioannis Thomas reports honoraria for talks or 
      advisory boards from BMS and Pierre Fabre; and research funding (institutional) 
      from BMS, Pfizer, MSD, Amgen, ARGN-X, LEO, Novartis, UCB, 4SC, AstraZeneca, 
      BioNTech, Genentech, Roche, Biotech, CureVac, HUYA, Incyte, Idera, Iovance, 
      InflaRx, Cerpass, Kartos, Nektar, Philogen, Pierre Fabre, Regeneron, Replimune, 
      and Sanofi. Heike Niessner reports institutional funding from Novartis and Pierre 
      Fabre outside the submitted work. Tobias Sinnberg reports institutional funding 
      from Novartis and Pierre Fabre outside the submitted work. Andrea Forschner 
      served as a consultant to Roche, Novartis, MSD, BMS, and Pierre Fabre; received 
      travel support from Roche, Novartis, BMS, and Pierre Fabre; received speaker fees 
      from Roche, Novartis, BMS, MSD, and CeGaT; and reports institutional research 
      grants from BMS Stiftung Immunonkologie. Lukas Flatz reports grants or contracts 
      from Hookipa Pharma, SAKK/Immunophotonics, DFG Grant (Deutsche 
      Forschungsgemeinschaft), Philogen, and Mundipharma; consulting fees from 
      Philogen, Sanofi, Novartis, and BMS; participation on the Data Safety Board, 
      University of Basel; and stocks or stock options from Hookipa Pharma, outside the 
      submitted work. Teresa Amaral reports personal honoraria from BMS, CeCaVa, 
      Novartis, and Pierre Fabre; institutional financial support from iFIT, NeraCare, 
      Novartis, Sanofi, and SkylineDx, and an institutional research grant from 
      Novartis, outside the submitted work. Eftychia Chatziioannou, Ulrike Keim, Olivia 
      Seeber, Andreas Meiwes, Isabell Boessenecker, Stephanie Sanchez Gonzalez, and 
      Francisco Merraz Torres have no relationships to disclose.
EDAT- 2023/05/05 00:42
MHDA- 2023/05/22 06:42
PMCR- 2023/05/04
CRDT- 2023/05/04 23:33
PHST- 2023/03/25 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/05/05 00:42 [pubmed]
PHST- 2023/05/04 23:33 [entrez]
PHST- 2023/05/04 00:00 [pmc-release]
AID - 10.1007/s40257-023-00775-7 [pii]
AID - 775 [pii]
AID - 10.1007/s40257-023-00775-7 [doi]
PST - ppublish
SO  - Am J Clin Dermatol. 2023 May;24(3):453-467. doi: 10.1007/s40257-023-00775-7. Epub 
      2023 May 4.