Immunotherapy in Merkel cell carcinoma: role of Avelumab

Palla, Amruth R.; Doll, Donald C.

doi:10.2147/itt.s135639

Cited by 13 publications

(13 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Patients receiving durvalumab demonstrated significant improvement in progression-free survival (16.8 months) compared with patients who received placebo, 16.8 months (5.6 months) [74]. Avelumab received accelerated approval by the FDA for the treatment of metastatic Merkel cell carcinoma (MCC), a rare type of skin cancer in 2017 [75]. The binding of avelumab to PD-L1 can inhibit the interaction of PD-L1 with PD-1, consequently restoring the immune response as well as antitumor activity [75].…”

Section: Main Textmentioning

confidence: 99%

“…Avelumab received accelerated approval by the FDA for the treatment of metastatic Merkel cell carcinoma (MCC), a rare type of skin cancer in 2017 [75]. The binding of avelumab to PD-L1 can inhibit the interaction of PD-L1 with PD-1, consequently restoring the immune response as well as antitumor activity [75]. The overall response rate (ORR) was 33%, while the estimated one-year overall and progression-free survival were 52 and 30%, respectively [75].…”

Section: Main Textmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment

Looi

Chung

Leong

et al. 2019

J Exp Clin Cancer Res

122

111

View full text Add to dashboard Cite

Background Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME). Main body In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME. Conclusions It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.

show abstract

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment

Looi

Chung

Leong

et al. 2019

J Exp Clin Cancer Res

122

111

View full text Add to dashboard Cite

show abstract

“…MCC is a very rare skin cancer with a high mortality rate of ≥15%. Surgery and radiation therapy can control localized MCC as high as 95% for the first‐line treatment; however, more than half of the MCC cases relapse with extremely low response rates to chemotherapy. Avelumab was expected to be the second‐line treatment for metastatic MCC.…”

Section: Introductionmentioning

confidence: 99%

Case of fulminant type 1 diabetes induced by the anti‐programmed death‐ligand 1 antibody, avelumab

Shibayama

Kameda

Ota

et al. 2019

J of Diabetes Invest

View full text Add to dashboard Cite

With the expansive use of immune checkpoint inhibitors, the frequency of immune‐related adverse events, including autoimmune type 1 diabetes, has been exponentially increased. The anti‐programmed death‐ligand 1 antibody, avelumab, has recently been approved for metastatic Merkel cell carcinoma therapy. Here, we report a patient that developed fulminant type 1 diabetes during avelumab treatment. An 81‐year‐old woman with no history of diabetes received avelumab for metastatic Merkel cell carcinoma. Elevated plasma glucose level (483 mg/dL), hemoglobin A1c level (7.5%) and ketosis were observed after 10 courses of avelumab without any symptoms related to hyperglycemia. As the laboratory tests showed insulin depletion, we diagnosed her with fulminant type 1 diabetes induced by avelumab. This is the first reported case of avelumab‐induced type 1 diabetes, illustrating the necessity for close monitoring of glycemic control during avelumab therapy, as well as other immune checkpoint inhibitors.

show abstract

“…PD-1 ist ein Rezeptor, der vorrangig von T-Zellen exprimiert wird; PD-L1, sein Ligand, wird auf Tumorzellen und dem Tumormikroenvironment exprimiert. Eine Blockade der Interaktion durch entweder anti-PD1 oder anti-PD-L1 führt zu der Induktion einer Immunantwort gegen Tumorzellen [11]. Während die Interaktion zwischen PD-1 und PD-L2 bei PD-L1-Blockade unberührt bleibt, wird sie durch PD-1-blockierende Antikörper unterbrochen.…”

Section: Falldarstellungunclassified

Sequentielle Immuncheckpoint-Inhibition beim Merkelzellkarzinom

2020

View full text Add to dashboard Cite

ZusammenfassungDas Merkelzellkarzinom (MCC) ist der Hauttumor mit der höchsten Mortalität. Auf eine Therapie mit Immuncheckpoint-Inhibitoren spricht zwar mehr als die Hälfte der metastasierten Patienten an, es ist aber nicht bekannt, wie bei Patienten, die nur unzureichend oder nicht mehr von einer PD-1- oder PD-L1-Blockade profitieren, vorzugehen ist.Wir stellen einen 67-jährigen Patienten mit multiplen Lebermetastasen eines MCC vor. Die Erstdiagnose wurde 5 Jahre vor Auftreten der Fernmetastasierung gestellt. Nachdem es unter einer Chemotherapie mit Paclitaxel und Carboplatin als Erstlinientherapie zu einem Progress der Lebermetastasen gekommen war, wurde eine Therapie mit dem Immuncheckpoint-Inhibitor Avelumab (anti-PD-L1-Antikörper) eingeleitet. Unter dieser Therapie zeigte sich trotz initialen guten Ansprechens im 1. Staging nach 6 Gaben ein Progress einer Lebermetastase bei stabilem Befund weiterer Lebermetastasen. Der Patient wurde wegen der progredienten Lebermetastase hemihepatektomiert. In der Folge bildeten sich weitere Lebermetastasen, sodass eine Therapie mit dem PD-1-Inhibitor Pembrolizumab eingeleitet wurde. Unter dieser Therapie zeigte sich nun eine über mehr als 2 Jahre anhaltende und fortbestehende komplette Remission.Dieser Fall könnte darauf hinweisen, dass beide Moleküle unterschiedliche Wirkmechanismen haben und ein sequentielles Vorgehen eine sinnvolle Strategie sein kann. Wir empfehlen, zu dieser Frage eine gezielte klinische Studie durchzuführen.

show abstract

Immunotherapy in Merkel cell carcinoma: role of Avelumab

Cited by 13 publications

References 16 publications

Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment

Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment

Case of fulminant type 1 diabetes induced by the anti‐programmed death‐ligand 1 antibody, avelumab

Sequentielle Immuncheckpoint-Inhibition beim Merkelzellkarzinom

Contact Info

Product

Resources

About