2011;21:223C227. biomarkers. RESULTS Thirty-three individuals were enrolled. No dose-limiting toxicities were observed. Ninety-seven percent of individuals experienced treatment-related adverse events (TRAEs). The most common TRAEs were slight (grade 1 or 2 2) and included diarrhea, proteinuria, hand and foot syndrome, fatigue, AST or ALT elevation, hypertension, hypo- or hyperthyroidism, and rash. Grade 3 or higher TRAEs occurred in 39.4% of individuals. From the cutoff day, among 29 individuals with chemotherapy-na?ve mucosal melanoma, 14 individuals (48.3%; 95% CI, 29.4% to 67.5%) accomplished objective response, and the median progression-free survival time was 7.5 months (95% CI, 3.7 months to not reached) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Summary The combination of toripalimab plus axitinib was tolerable and showed encouraging antitumor activity in individuals with treatment-na?ve metastatic mucosal melanoma. Individuals enrolled in this study were all Asian, and this combination therapy must be validated inside a randomized phase III trial that includes a non-Asian populace before it can become a standard of care. Intro Mucosal LY2794193 melanoma is definitely a rare melanoma subtype, composing approximately 1.3% of all melanomas in white populations.1 LY2794193 In contrast, it is the second most common subtype in Asian populations, constituting 22% to 25% of all melanomas in Asian patients.2,3 Compared with chronic ultraviolet exposureCassociated cutaneous melanoma, mucosal melanoma is a more aggressive malignancy with lower tumor LY2794193 mutational burden (TMB)4 and poorer reactions to therapies.5-7 A genome-wide mutational scenery study has shown that, in contrast to heavily mutated ultraviolet-induced cutaneous melanoma, mucosal melanomas harbor unique mutations with unfamiliar etiology,4 which provides a molecular basis for the discordant clinical treatment results of melanoma in Asian versus white populations. Curtin et al8,9 reported infrequent mutations in mucosal melanomas (11%) but frequent mutations in cutaneous melanomas unrelated to chronic sun-induced damage (non-CSD; 59%), whereas amplifications or activating mutations were more common in mucosal melanomas (39%) than non-CSD melanomas (0%).9 However, two large-scale studies on and mutations in Chinese patients found a similar frequency of mutations (12.5%) but a lower frequency of aberrations Cdc14A2 (20.1%) in individuals with mucosal melanoma compared with white individuals.10,11 A retrospective study involving 12 individuals with mucosal melanoma harboring mutations demonstrated a median progression-free survival (PFS) time of 4.4 months and median overall survival (OS) time of 8.2 months, with an overall response rate (ORR) of 20.0%, after treatment with BRAF inhibitors.12 Several phase II tests included individuals with mucosal melanoma to evaluate the efficacy of a KIT inhibitor in individuals with aberrations. The results were unsatisfactory no matter race, with an ORR of 16.0% to 23.3% and a median PFS of only 2.8 to 3.7 months.13-15 In addition, in a large cohort study (N = 522), the median OS of patients with mucosal melanoma was significantly shorter than that of patients with nonmucosal melanoma (3.58 4.67 years, respectively), indicating an unmet need for effective systemic treatments for the mucosal subtype.3 Immune checkpoint inhibitors have improved the outcomes of advanced melanoma, but the benefits are mainly manifested in individuals with the cutaneous subtype rather than mucosal subtype. The combination of ipilimumab and LY2794193 antiCprogrammed cell death-1 (PD-1) inhibitors seems to improve results compared with monotherapy in mucosal melanoma. However, the data concerning immunotherapy among Chinese individuals are limited. The KEYNOTE-151 study (ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT02821000″,”term_id”:”NCT02821000″NCT02821000) showed a 13.3% ORR with pembrolizumab in Chinese individuals with mucosal melanoma refractory to chemotherapy.16 However, a phase II trial of toripalimab, also known as JS001 or TAB001, a humanized immunoglobulin G4 monoclonal antibody against PD-1,17 in 128 pretreated Chinese individuals with advanced melanoma showed a higher ORR for individuals with CSD (35.3%) and non-CSD (33.3%) subtypes than for individuals with the mucosal.
- Parvovirus B19 illness was only detected in 4% of the individuals raising the suspicion of an autoimmune etiology indie of known infections
- Forty-eight hours later, I-E(52-68) peptide and subsequently either vehicle, RAPA or AZD2014 were injected i