K. M. Leick1, E. P. Salerno1, J. M. Obeid1, D. H. Deacon1, C. L. Slingluff1 1University Of Virginia,Surgery,Charlottesville, VA, USA
Introduction: Topical imiquimod, a TLR7 agonist, has been reported to induce regression of some cutaneous in-transit metastases of melanoma, yet rates of tumor control and predictors of response are not established. We have reported that melanoma metastases may be grouped into Immunotypes representing patterns of immune cell infiltration: A (none), B (perivascular cuffing), and C (diffuse). The goals of this study were to provide pilot data toward testing the following hypotheses: 1) imiquimod may induce complete regressions of cutaneous melanoma metastases, 2) imiquimod extends time to major surgery, and 3) clinical responses to imiquimod are more frequent when the metastases have pre-existing immune cell infiltrates.
Methods: The UVA melanoma database was searched for patients with in-transit metastases treated with imiquimod (n=12) and matched for control patients with in-transit metastases who were not treated with imiquimod (n=11). Biopsies of metastases (IRB #10598 and 10803) were evaluable for 9 treated patients prior to initiating imiquimod. Immunohistochemistry staining (IHC) was performed on formalin-fixed paraffin-embedded sections of those tumors, using antibodies to CD45 and CD34 to assess patterns of immune cell infiltrates (Immunotypes).
Results:Among 12 patients treated with topical imiquimod, 2 (17%) had complete regressions of the metastases, while 6 (50%) had mixed responses. Complete or mixed responses typically enabled patients to delay or to avoid major surgical resections or limb perfusion. Complete responses were all in the tumors with Immunotypes B and C (2/7), and none were in those with Immunotype A (0/2). Median time to surgery for the imiquimod group (357 days) trended longer than for controls (49 days, p=0.076). For the evaluable imiquimod-treated patients, higher Immunotype (B and C vs. A) was associated with improved survival (p=0.0019).
Conclusion:These pilot data demonstrate that a small but meaningful subset of patients experience complete regressions of skin metastases with imiquimod alone. Further, the findings suggest that imiquimod therapy may provide sufficient control to avoid or to delay major surgical resections. Both complete responses were in patients whose tumors had significant immune cell infiltrates prior to initiating therapy. Overall, metastases with higher Immunotype (B or C) who were treated with imiquimod had enhanced survival. These pilot data support use of imiquimod for patients with superficial metastatic disease who are suboptimal candidates for major surgical resection or aggressive systemic therapy. These data also suggest that T cell infiltration in the metastases may be associated with better outcomes for patients treated with imiquimod.
