Purpose: For classical Hodgkin lymphoma (cHL), programmed death-l (PD-1) is a well-recognized attractive target. This multicenter, single-arm, phase II study evaluated the efficacy and safety of camrelizumab, a humanized highaffinity IgG4 mAb against PD-1, in Chinese patients with relapsed or refractory cHL.Patients and Methods: Patients who had failed to achieve a remission or experienced progression after autologous stem cell transplantation or had received at least two lines of systemic chemotherapies were given camrelizumab 200 mg every 2 weeks. The primary endpoint was objective response rate per independent review committee (IRC) assessment. This study is registered with ClinicalTrials.gov (NCT03155425).Results: Between June 9, 2017 and September 18, 2017, 75 patients were enrolled and treated. At a median follow-up of 12.9 months, 57 of 75 (76.0%; 95% CI, 64.7-85.1) patients achieved an IRC-assessed objective response, including 21 (28.0%) and 36 (48.0%) patients who had complete and partial remission, respectively. Median duration of response was not reached (range, 0.0 þ -12.8 þ months). Treatmentrelated adverse events (AE) occurred in all patients. The most common ones included cutaneous reactive capillary endothelial proliferation (97.3%, 73/75) and pyrexia (42.7%, 32/75). Grade 3 or 4 treatment-related AEs occurred in 20 patients (26.7%); the most common AE was decreased white blood cell count (4.0%, 3/75). There were no grade 5 treatment-related AEs.Conclusions: Camrelizumab demonstrated a high response rate, durable response and controllable safety in Chinese patients with relapsed or refractory cHL, becoming a new safe and effective treatment option in this setting.

Gasdermin E (GSDME) is a member of the gasdermin protein family, which mediates programmed cell death including apoptosis and pyroptosis. Recently, it was suggested that GSDME is activated by chemotherapeutic drugs to stimulate pyroptosis of cancer cells and trigger anti-tumor immunity, which is identified as a tumor suppressor. However, GSDME-mediated pyroptosis contributes to normal tissue damage, leading to pathological inflammations. Inhibiting GSDME-mediated pyroptosis might be a potential target in ameliorating inflammatory diseases. Therefore, targeting GSDME is a promising option for the treatment of diseases in the future. In this review, we introduce the roles of GSDME-driven programmed cell death in different diseases and the potential targeted therapies of GSDME, so as to provide a foundation for future research.

Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide-resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n 5 11), 8 mg/kg (n 5 17), and 10 mg/kg (n 5 15). CPT was administered via intravenous infusion on days 1-5, and thalidomide was given orally at 100 mg once daily in each 21-day cycle. The overall response rate (ORR) of 41 efficacy-evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher-dose regimen. Median progression-free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment-related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3-4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose-limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial.

MicroRNA-223 (miR-223) expression has been demonstrated to be stage-specific in B cell differentiation and associated with the outcome of chronic lymphocytic leukemia (CLL). However, the expression pattern of miR-223 in B cell lymphoproliferative disorders and its association with the outcome of Chinese patients with CLL have not been investigated. In this study, we demonstrated that miR-223 expression was significantly decreased in CLL, mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL). In CLL, miR-223 expression decreased significantly with progression from early to advanced clinical stages and was significantly lower in patients with elevated β(2)-microglobulin, unmutated immunoglobulin variable heavy chain (IgVH) gene or with disease progression or death. Using a cut-off determined by receiver operating characteristic (ROC) analysis optimizing concordance with IgVH mutational status, miR-223-negative and -positive groups were defined for 22 and 31 patients, respectively. The median progression-free survival (PFS) and overall survival of the miR-223-negative group were 13 and 40 months, respectively, significantly shorter than for the miR-223-positive group (both not reached; p = 0.002 and p = 0.018, respectively). Multivariate analysis revealed that the absence of miR-223 was the only independent factor capable of predicting shorter PFS. In conclusion, miR-223 is uniformly down-regulated in B-LPDs and is a useful prognostic factor for patients with CLL.