Neo-Adjuvant Immunotherapy emerges as best medical practice and will be the new standard of care for macroscopic stage III Melanoma.
Abstract Survival of macroscopic stage III melanoma is poor. Five-year overall survival and relapse-free survival rates for surgery alone range from 40 to 59% and 30 to–39%, respectively. The current standard of care is therapeutic lymph node dissection (TLND) followed by a year of adjuvant systemic therapy. Multiple phase 2 trials have shown that neo-adjuvant immunotherapy induces major pathologic response (MPR) rates (pathologic complete response (pCR): pCR, 0% viable tumour cells; near-pCR, <10% viable tumour cells), which translate into durable relapse free survival rates. Single agent anti-PD-1 achieves 20–30% MPR, the combination of ipilimumab and nivolumab doubles the MPR [...]
Alternatives and Reduced need for Sentinel Lymph Node Biopsy (SLNB) Staging for Melanoma
Abstract Sentinel lymph node biopsy (SLNB) has been introduced in the 1990s to identify patients who might benefit from completion lymph node dissection. Neither SLNB nor CLND improved survival, but SLNB staging did provide the best staging, above Breslow thickness and ulceration. The SLN status and SLN tumour burden were used in all trials until date looking at modern adjuvant systemic therapy with immune checkpoint inhibition (ICI) or targeted therapies (TT). Adjuvant ICI and TT are shifting towards stage II melanoma. The question is whether there is still role for SLNB in melanoma, in this day and age, and [...]
Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.
Abstract Background: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. Methods: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body [...]
ASO Visual Abstract: Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma-An International Multi-institutional Collaboration.
Abstract In this international, multi-institutional, retrospective cohort study of 676 patients with thin melanoma undergoing sentinel lymph node biopsy, only 7.8% of patients had a positive sentinel lymph node. Mitotic rate and Breslow thickness were predictive of nodal metastasis. Read Full Paper
Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?
Abstract Introduction: Sentinel lymph node biopsy (SLNB) is important for staging in patients with primary cutaneous melanoma. Did having previously undergone SLNB also affect outcomes in patients once they have progressed to metastatic melanoma in the era prior to adjuvant therapy? Methods: Data were retrieved from the Dutch Melanoma Treatment Registry, a prospectively collected, nationwide database of patients with unresectable stage IIIC or IV (advanced) melanoma between 2012 and 2018. Melanoma-specific survival (MSS) was compared between patients with advanced cutaneous melanoma, previously treated with a wide local excision (WLE) or WLE combined with SLNB as initial treatment of their primary tumor. [...]
Five-Year Analysis of Adjuvant Pembrolizumab or Placebo in Stage III Melanoma.
Abstract Background In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence- and distant metastasis-free survival than placebo in patients with resected high-risk stage III melanoma. To confirm the stability of these benefits, longer-term data were needed. Methods We randomly assigned 1019 patients to receive 200 mg of pembrolizumab or placebo intravenously every 3 weeks for a total of 18 doses (approximately 1 year) and had previously reported data with a 15-, 36-, and 42-month median follow-up. We now report data at a median follow-up of 4.9 years. [...]
Neoadjuvant nivolumab + T-VEC combination therapy for resectable early stage or metastatic (IIIB-IVM1a) melanoma with injectable disease: study protocol of the NIVEC trial.
Abstract Background: Trials investigating neoadjuvant treatment with immune checkpoint inhibitors (ICI) in patients with melanoma have shown high clinical and pathologic response rates. Treatment with talimogene laherparepvec (T-VEC), a modified herpes simplex virus type-1 (HSV-1), is approved for patients with unresectable stage IIIB-IVM1a melanoma and has the potential to make tumors more susceptible for ICI. Combination ICI and intralesional T-VEC has already been investigated in patients with unresectable stage IIIB-IV disease, however, no data is available yet on the potential benefit of this combination therapy in neoadjuvant setting. Methods: This single center, single arm, phase II study aims to show an [...]