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Dr. Julia Ressler

Talimogene laherparepvec (T-VEC) in advanced melanoma : complete response in a heart and kidney transplant patient . A case report. Julia Ressler 1 , Rita Silmbrod 1 , Andreas Stepan 1 , Felix Tuchmann 1 , Astrid Cicha 1 , Keziban Uyanik-Ünal 2 , Christoph Hoeller 1

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Dr. Julia Ressler

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  1. Talimogenelaherparepvec (T-VEC) in advancedmelanoma: completeresponse in a heart and kidneytransplantpatient. A casereport Julia Ressler1, Rita Silmbrod1, Andreas Stepan1, Felix Tuchmann1, Astrid Cicha1, Keziban Uyanik-Ünal2, Christoph Hoeller1 Department of Dermatology1 and Surgery2 Medical University Vienna British Journal of Dermatology. DOI: 10.111/bjd.17783

  2. Dr. Julia Ressler

  3. Introduction What’s already known? • Talimogenelaherparepvec (T-VEC) isan intralesionaloncolyticvirotherapy, licensed in the European Union forlocoregionaladvancedmelanoma of American Joint Committee on Cancerstages IIIB, IIIC and IVM1a • Organ transplantrecipients (OTRs) have so far beenexcludedfrom all clinicaltrialsdealingwithimmunotherapiesdue to therisk of transplantrejection

  4. Case report 58 yearold, caucasian man • Heart and kidneytransplantation 2015 Melanoma (BI 1.6mm, pT2a) on theleft arm Sentinellymphnodebiopsypositive Axillarylymphnodedissection 26 negative lymphnodes Laboratory findings S100 and LDH withinrange CT Scan No sign of metastaticlesions

  5. Case report Histopathology Cutaneous, epidermotropic metastaticlesions Therapy Cryotherapyevery4 weeksand Imiquimod 5% 5x/week(April-November)

  6. Case report November 2016

  7. Case report Tumorboard – Stage IIIC Comorbidities:Heart and kidneytransplantion in 2014, arterialhypertension ECOG 0 B-raf, c-kit and N-ras wild type Notargetedtherapy Risk of graft rejection Nosystemicimmunotherapywith Checkpoint-Inhibitor  OncolyticimmunotherapywithTalimogenelaherparepvec (T-VEC)

  8. First approvedoncolyticvirotherapy in the EU (12/2015) forstage IIIB-IVM1a melanomawithoutbrain, pulmonary, intestinal orbonemetastases Modified Herpes simplexvirus 1 Deletionof twoInfectedCell Proteins (ICP) 34.5 and 47 Insertion of human granulocytemacrophagecolonystimulatingfactor(hGM-CSF) Case report Talimogenelaherparepvec (T-VEC)

  9. Nov 2016 Cycle 1 June 2017 After 11 Cycles Left arm Left arm -> ->

  10. September 201813 monthsafter 11 cycles of T-VEC Completeresponse CT scan: noevidenceofmetastaticdisease Transplantedorgans No sign of graft rejectionorchange in function of thetransplantedorgans

  11. Discussion • OTRs have an estimated 2.4 times higher risk of developing melanoma [Dahlke et al. Transplant Res 2014; 3:10] • Immunosuppressive drugs increase the risk of developing skin cancer [Spain et al. Ann Oncol 2016; 27:1135–7]

  12. Casereport • Checkpoint inhibitors in OTRs are often considered ineffective, due to the existing immunosuppressive medication [Min et al. Aging. 2015 Aug; 7: 521-522]and could at the same time pose a risk of transplant rejection [Spain L et al. Ann Oncol. 2016 Jun; 27: 1135-1137] • BRAF/MEK inhibitors in OTRs may prevent acquired resistance to these agents and could help reduce the risk of allograft rejection [Chae et al. Cancer Treat Rev. 2018 Feb; 63: 116-121.]

  13. Casereport • Regarding oncolyticvirotherapy in OTRs, Schvartsman et al. reported successful treatment of a patient with an inoperable, recurrent melanoma after therapy with T-VEC [Schvartsman et al. J ImmunotherCancer 2017; 5:45]

  14. ConclusionsWhat does this study add? • Weconcludethat T-VEC canbe a potentiallyeffective and safetreatment in patientswith a history of organtransplantation. • Nevertheless, due to thisspecialsituation, therisks and benefitsshouldalwaysbediscussedwith an interdisciplinarytumourboard.

  15. Call for correspondence • Why not join the debate on this article through our correspondence section? • Rapid responses should not exceed 350 words, four references and one figure • Further details can be found here

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