Citations 2
A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first‐line treatment for patients with melanoma in‐transit metastases
DePalo, Danielle K. , Dugan, Michelle M. , Naqvi, Syeda Mahrukh Hussnain , Ollila, David W. , Hieken, Tina J. , Block, Matthew S. , Houdt, Winan J. van , Reijers, Sophie J. M. , Asher, Nethanel , Duncan, Zoey , Anderson, Matilda, Snow, Hayden , Held, Jenny M., Farma, Jeffrey M. , Vetto, John T. , Hui, Jane Yuet Ching , Kolbow, Madison , Saw, Robyn P.M. , Lo, Serigne , Long, Georgina V. , Karapetyan, Lilit , Akkooi, Alexander C. J. van , van Houdt, Winan J , Asher, Nethanel , Hui, Jane Yuet Ching , Kolbow, Madison , Lo, Serigne N , Thompson, John F , Zager, Jonathan S , Hieken, Tina J , Long, Georgina V , Wouters, Michel W.J.M. , Broman, Kristy K. , Gyorki, David E. , Held, Jenny, Thompson, John F. , Kim, Youngchul , Ny, Lars , Bagge, Roger Olofsson , Zager, Jonathan S.
Cancer | November 10, 2024 | Volume: 131 | Issue: 1 | Pages: No page available
AbstractBackgroundIsolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in‐transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first‐line ILI/ILP, ICI, and TVEC.MethodsRetrospective review from 12 international institutions included patients treated from 1990 to 2022 with first‐line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM.ResultsA total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow‐up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p = .002). Breslow thickness was lowest with TVEC (p = .007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p = .01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p = .029) and a longer local progression‐free survival (PFS) (hazard ratio [HR], 0.40; p = .003). ILI/ILP had shorter local PFS (HR, 1.72; p = .012), PFS (HR, 1.79; p < .001), distant metastasis‐free survival (DMFS) (HR, 1.75; p = .014), overall survival (HR, 1.82; p = .009), and melanoma‐specific survival (HR, 2.29; p = .004). Stage IIIB disease had longer DMFS (HR, 0.24; p < .001) compared to IIIC/D.ConclusionsTVEC as first‐line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first‐line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.
Intralesional therapy, limb infusion/perfusion, and immune checkpoint inhibitors as first-line therapy in surgically unresectable melanoma in-transit metastases.
DePalo, Danielle K. , Naqvi, Syeda Mahrukh Hussnain , Ollila, David W. , Block, Matthew S. , Duncan, Zoey , Anderson, Matilda, Vetto, John T. , Saw, Robyn P.M. , Lo, Serigne , Akkooi, Alexander Christopher Jonathan Van, Akkooi, Alexander C. J. van , Lo, Serigne N , Hieken, Tina J. , Houdt, Winan J. van , Wouters, Michel W.J.M. , Asher, Nethanel , Broman, Kristy K. , Gyorki, David E. , Hui, Jane Yuet Ching , Kim, Youngchul , Bagge, Roger Olofsson , Zager, Jonathan S.
Journal of Clinical Oncology | June 4, 2023 | Volume: 41 | Issue: 16_suppl | Pages: 9574-9574
10.1200/jco.2023.41.16_suppl.9574
9574 Background: Surgery remains the gold standard for resectable melanoma in-transit metastases (ITM). Unresectable ITM is a heterogenous disease with multiple treatment (tx) options including systemic therapies such as immune checkpoint inhibitors (ICI), regional therapies such as isolated limb infusion or perfusion (ILI/P), and intratumoral therapies such as talimogene laherparepvec (IT). Until now, there has been no direct comparison of these first-line tx for unresectable ITM. Methods: A retrospective chart review of patients (pts) with ITM treated first-line with IT, ILI/P, or ICI was performed at 11 institutions. Pts with unresectable ITM, synchronous nodal or distant metastatic disease were excluded. Results: 560 pts (54% women) were identified, 86 received IT, 353 received ILI/P, and 121 received ICI from 1990-2022. ICI pts were youngest, IT pts were oldest (p<0.001). Limb was the most common site of ITM. There was no difference in largest ITM size, but number of lesions (burden of disease (BOD)) was highest in ILI/P pts and lowest in IT pts (p=0.003). Toxicity (tox) requiring <90 days (p<0.001) or > 90 days (p=0.034) of pharmacologic tx as well as tox requiring hospitalization (p<0.001) was greatest in ICI pts. Lymphedema was more likely in ILI/P pts (p=0.016). Median follow-up was much longer for ILI/P pts at 8.0 yrs compared to 2.5 yrs for IT pts and 3.1 yrs for ICI pts. Overall response rate (ORR) was 82.2% in ILI/P pts, significantly higher than IT (72.1%, p=0.047) or ICI pts (63.6%, p<0.001). Overall survival was similar between modalities (p=0.167); however, ILI/P pts had worse progression-free survival (PFS) (p<0.0001) and melanoma-specific survival (MSS) (p=0.003). On multivariable analysis of MSS by number of ITM present, MSS remained worst if ILI/P was used for low BOD, ≤3 ITM (p=0.005), but no difference was seen between tx modalities for higher BOD, >3 ITM (p=0.211). Conclusions: ICI was used more often in younger pts with less BOD, IT in older pts with less BOD, and ILI/P in older pts with high BOD. Short and long-term tox was greater in ICI. ILI/P had the best ORR, but ICI and IT resulted in greater overall MSS. Multidisciplinary consideration of risks and benefits of each modality should guide ITM tx selection. [Table: see text]