H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Danielle K DePalo , Syeda Mahrukh Hussnain Naqvi , David W. Ollila , Tina J. Hieken , Matthew Stephen Block , Winan J. van Houdt , Michel W.J.M. Wouters , Nethanel Asher , Kristy Kummerow Broman , Zoey Duncan , Matilda Anderson , David E. Gyorki , John T. Vetto , Jane Yuet Ching Hui , Robyn P.M. Saw , Serigne N. Lo , Youngchul Kim , Alexander Christopher Jonathan Van Akkooi , Roger Olofsson Bagge , Jonathan S. Zager
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.
IT n= 86 | ILI/P n=353 | ICI n=121 | p-value | |
---|---|---|---|---|
Age (yrs, median) | 74 | 67 | 64 | p<0.001 |
Number of ITM (mean) | 4.2 | 12.6 | 7.1 | p=0.003 |
Tox Requiring <90 Days Pharmacologic Tx (%) | 18.0 | 20.4 | 44.1 | p<0.001 |
Tox Requiring >90 Days Pharmacologic Tx (%) | 0.0 | 12.7 | 16.9 | p=0.034 |
Tox Requiring Hospitalization (%) | 1.4 | 9.2 | 22.1 | p<0.001 |
ORR (%) | 72.1 | 82.2 | 63.6 | IT vs. ILI/P p=0.047 ILI/P vs. ICI p<0.001 ICI vs. IT p=0.231 |
Median Follow-Up (yrs) | 2.5 | 8.0 | 3.1 | - |
Median PFS (yrs) | 2.1 | 0.7 | 1.2 | p<0.0001 |
MSS (cumulative incidence, events/total) | 13/85 | 148/347 | 15/106 | p=0.003 |
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