Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma

Rozeman, Elisa A.; Hoefsmit, Esmée P.; Reijers, Irene L. M.; Saw, Robyn P.M.; Versluis, Judith M.; Krijgsman, Oscar; Dimitriadis, Petros; Sikorska, Karolina; Wiel, Bart A. van de; Eriksson, Hanna; Gonzalez, Maria; Acosta, A. Torres; Grijpink-Ongering, Lindsay G; Shannon, Kerwin F.; Haanen, John B.A.G.; Stretch, Jonathan R.; Ch’ng, Sydney; Nieweg, Omgo E.; Mallo, Henk; Adriaansz, S.; Kerkhoven, Ron; Cornelissen, Sten; Broeks, Annegien; Klop, W. Martin C.; Zuur, Charlotte L.; Houdt, Winan J. van; Peeper, Daniel S.; Spillane, Andrew J.; Akkooi, A.C.J. van; Scolyer, Richard A.; Schumacher, Ton N.; Menzies, Alexander M.; Long, Georgina V.; Blank, Christian U.

doi:10.1038/s41591-020-01211-7

Cited by 233 publications

(200 citation statements)

References 39 publications

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“…While the generally increased safety profile of αPD-1 agents over αCTLA-4 agents has been encouraging, the improved but imperfect benefit noted with standard-of-care dual ICI favors a continued search for adjunctive therapies for patients with advanced disease, even at the risk of increased toxicities. Alternative dosing and treatment sequences (such as neoadjuvant vs. adjuvant ICI in patients with resectable locally advanced disease) may also provide insight into new treatment algorithms with altered safety and efficacy profiles among specific patient groups [113].…”

Section: Discussionmentioning

confidence: 99%

Thinking Small: Small Molecules as Potential Synergistic Adjuncts to Checkpoint Inhibition in Melanoma

Chacon

Melucci

Qin

et al. 2021

IJMS

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Metastatic melanoma remains the deadliest form of skin cancer. Immune checkpoint inhibition (ICI) immunotherapy has defined a new age in melanoma treatment, but responses remain inconsistent and some patients develop treatment resistance. The myriad of newly developed small molecular (SM) inhibitors of specific effector targets now affords a plethora of opportunities to increase therapeutic responses, even in resistant melanoma. In this review, we will discuss the multitude of SM classes currently under investigation, current and prospective clinical combinations of ICI and SM therapies, and their potential for synergism in melanoma eradication based on established mechanisms of immunotherapy resistance.

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Section: Discussionmentioning

confidence: 99%

Thinking Small: Small Molecules as Potential Synergistic Adjuncts to Checkpoint Inhibition in Melanoma

Chacon

Melucci

Qin

et al. 2021

IJMS

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“…In contrast, in a meta-analysis including more than 10,000 patients treated with immunotherapy for several types of advanced cancers, a higher relative reduction of the risk of death was observed in male compared to female patients [ 30 ]. Since a higher tumor mutational burden has been reported in male patients [ 31 , 32 ] and this is a predictor of benefit from immune checkpoint inhibitors [ 33 , 34 ], this could be a possible explanation for improved overall survival rates in male patients. Aging has been reported to accompany certain immune changes such as a decrease in the number and functionality of naïve CD8 + T-cells [ 35 , 36 ] and reduced phagocytic function and HLA-II expression of DCs [ 37 ], indicating elder individuals have an impaired T-cell response to cross-presented antigens (immunosenescence).…”

Section: Discussionmentioning

confidence: 99%

“…Pathological response predictive for clinical outcome to immunotherapy has been reported early after initiation of anti-PD-1 in melanoma [ 34 , 46 ] and the accumulation of CD8 + T-cells expressing inhibitory receptors (exhausted T-cells, T ex ) was detected in the peripheral blood within 3 weeks after immunotherapy initiation [ 46 , 47 , 48 ]. In the current study, we observed increased proliferation of CD8 + T-cells in the blood as early as 7 days after anti-PD-1 treatment initiation in melanoma patients.…”

Section: Discussionmentioning

confidence: 99%

Immune Monitoring in Melanoma and Urothelial Cancer Patients Treated with Anti-PD-1 Immunotherapy and SBRT Discloses Tumor Specific Immune Signatures

Meireson

Tavernier

Gassen

et al. 2021

Cancers

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(1) Background: Blockade of the PD-1/PD-L1 pathway has revolutionized the oncology field in the last decade. However, the proportion of patients experiencing a durable response is still limited. In the current study, we performed an extensive immune monitoring in patients with stage III/IV melanoma and stage IV UC who received anti-PD-1 immunotherapy with SBRT. (2) Methods: In total 145 blood samples from 38 patients, collected at fixed time points before and during treatment, were phenotyped via high-parameter flow cytometry, luminex assay and UPLC-MS/MS. (3) Results: Baseline systemic immunity in melanoma and UC patients was different with a more prominent myeloid compartment and a higher neutrophil to lymphocyte ratio in UC. Proliferation (Ki67+) of CD8+ T-cells and of the PD-1+/PD-L1+ CD8+ subset at baseline correlated with progression free survival in melanoma. In contrast a higher frequency of PD-1/PD-L1 expressing non-proliferating (Ki67−) CD8+ and CD4+ T-cells before treatment was associated with worse outcome in melanoma. In UC, the expansion of Ki67+ CD8+ T-cells and of the PD-L1+ subset relative to tumor burden correlated with clinical outcome. (4) Conclusion: This study reveals a clearly different immune landscape in melanoma and UC at baseline, which may impact immunotherapy response. Signatures of proliferation in the CD8+ T-cell compartment prior to and early after anti-PD-1 initiation were positively correlated with clinical outcome in both cohorts. PD-1/PD-L1 expression on circulating immune cell subsets seems of clinical relevance in the melanoma cohort.

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“…Although the results are encouraging, there is a need to understand who can benefit more from the therapy, with acceptable side effects. Rozeman et al performed a large analysis of biomarkers in the neoadjuvant setting for stage III melanoma patients [ 65 ]. The group identified a gene expression signature of INF-γ, which, independently of TMB, is associated with pathologic response and OS.…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Predictive Biomarkers in Stage III Melanoma: Current Insights and Clinical Implications

Tonella

Pala

Ponti

et al. 2021

IJMS

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Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune therapies has dramatically improved the overall survival, but the identification of patients with a high risk of relapse who will benefit from adjuvant therapy and the determination of the best treatment choice remain crucial. Currently, patient prognosis is based on clinico-pathological features, highlighting the urgent need of predictive and prognostic markers to improve patient management. In recent years, many groups have focused their attention on identifying molecular biomarkers with prognostic and predictive potential. In this review, we examined the main candidate biomarkers reported in the literature.

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Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma

Cited by 233 publications

References 39 publications

Thinking Small: Small Molecules as Potential Synergistic Adjuncts to Checkpoint Inhibition in Melanoma

Thinking Small: Small Molecules as Potential Synergistic Adjuncts to Checkpoint Inhibition in Melanoma

Immune Monitoring in Melanoma and Urothelial Cancer Patients Treated with Anti-PD-1 Immunotherapy and SBRT Discloses Tumor Specific Immune Signatures

Prognostic and Predictive Biomarkers in Stage III Melanoma: Current Insights and Clinical Implications

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