Tuesday, January 30, 2018

Chemo via isolated limb perfusion followed by ipi = response rate of 85% in 26 melanoma patients

Isolated limb perfusion with chemotherapy is not a new treatment in melanoma.  I reported on its use for in-transit melanoma here in 2014:  In-Transit Melanoma..a little info.  I watched videos about its use while waiting for my treatments when I was at Moffitt between 2010 and 2013.  In this latest report, I am a little unclear about the status of the patients.  Maybe they were just your average melanoma patient with "advanced melanoma" in random organs...or perhaps (and this seems more likely...though not clearly stated) they were patients who had lesions specifically in the limb that was treated with the chemo infusion.  At any rate....here's the report...

Robust antitumor responses result from local chemotherapy and CTLA-4 blockade.  Arivan, Brady, Siegelbaum, Hu, et al. Cancer Immunol Res. 2018 Jan 16.

Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been less than 50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio. These changes were associated with improved survival of the mice. To translate these findings to a clinical setting, 26 patients with advanced melanoma were treated locally by isolated limb infusion with the nitrogen mustard alkylating agent melphalan followed by systemic administration of CTLA-4 blocking antibody (ipilimumab) in a phase II trial. This combination of local chemotherapy with systemic checkpoint blockade inhibitor resulted in a response rate of 85% at 3 months (62% complete and 23% partial response rate), and a 58% progression-free survival at one year. The clinical response was associated with increased T-cell infiltration, similar to that seen in the murine models. Together, our findings suggest that local chemotherapy combined with checkpoint blockade-based immunotherapy results in a durable response to cancer therapy.

If I were dealing with lesions localized in an extremity, be it nodular or in-transit lesions, this is certainly a treatment option I would discuss with my oncologist.  Hang tough, guys.  - c 

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