Articles related to CHECKPOINT INHIBITORS

This review summarizes the clinical presentation, workup, staging, and recent advancements in the treatment of PCNSL. Although treatment advances include the use of BTK inhibitors and immunomodulators, relapse is common and 5-year survival is 40% or lower. Thus, accurate early diagnosis and initiation of treatment is time sensitive for optimal neurologic recovery and disease control.

Resistance to immune checkpoint inhibitors is common. In a prior phase Ib study, the combination of talimogene laherparepvec (T-VEC) pembrolizumab demonstrated an encouraging complete response rate and acceptable safety profile in patients with advanced melanoma. In this phase III, randomized, double-blind, multicenter, international study, the combination of T-VEC-pembrolizumab did not statistically improve PFS or OS vs placebo-pembrolizumab. However, T-VEC-pembrolizumab demonstrated a numerical PFS improvement without new safety signals.

Talking about the limitations of the International Workshop on CLL (iwCLL) response criteria for chronic lymphocytic leukemia (CLL) in the era of novel medications is Dr. Alexey V. Danilov, Professor and Co-Director of the Toni Stephenson Lymphoma Center at the City of Hope National Medical Center in Duarte, California.

Reversal of HLA-I loss is crucial for an effective antitumor cytotoxic T cell response. Thus, HLA-I–upregulating drugs could augment immunotherapy response. The authors describe here a small-molecule USP7 inhibitor as a promising avenue for pharmacologic upregulation of HLA-I in MCC.

MDM2 is an important regulator of p53 and can be an effective therapeutic target in cancers. Pharmacological inhibition of MDM2 for stabilization of p53 has been of interest for several years and several MDM2 inhibitors targeting the MDM2-p53 interaction are currently in clinical trials. Approximately 80% of Merkel cell carcinoma (MCC) tumors have wild type p53 and could potentially respond to treatment with MDM2 inhibitors. In this study, milademetan showed a dose-dependent inhibition of tumor growth in MKL-1 xenograft and patient-derived xenograft models and is a potent MDM2 inhibitor in MCC.

The meta-analysis included data from nearly 13,000 patients across 30 published trials. Grade 3 or 4 AEs occurred in nearly 70% of patents receiving TKIs compared with 37% for those receiving ICIs.