Valganciclovir as Add-on to Second Line Therapy in Patients with Recurrent Glioblastoma

IntroductionGlioblastoma invariably recurs despite aggressive and multimodal first line treatment and no standardized second line therapy exists. We previously reported that treatment with the antiviral drug valganciclovir as an add-on to standard therapy significantly prolonged overall survival in 102 patients with newly diagnosed glioblastoma. Here we present the results of retrospective survival analyses including patients with glioblastoma that initiated valganciclovir therapy after recurrence. MethodsBetween April 13, 2007 and March 31, 2021, 29 patients with recurrent glioblastoma received valganciclovir as an add-on to second line therapy. Contemporary controls were 111 patients with glioblastoma who received similar second line therapy at our institution. We retrospectively analyzed survival data of these patients. ResultsPatients with recurrent glioblastoma who received valganciclovir had longer median overall survival after recurrence than controls (12.1 vs 7.4 months, respectively, p=0.0017). The drug was well tolerated. Both patients who underwent re-operation and patients that were not re-operated after recurrence benefitted significantly from valganciclovir therapy. Valganciclovir prolonged survival after recurrence both in patients with an unmethylated or methylated MGMT promoter gene. ConclusionValganciclovir was safe to use and prolonged median survival after recurrence of patients with recurrent glioblastoma, re-operated or not after recurrence and with methylated or unmethylated MGMT promoter gene.

Toripalimab: the First Domestic Anti-Tumor PD-1 Antibody in China

Toripalimab (Tuoyi™) is a selective, recombinant, humanized monoclonal antibody against programmed death protein 1 (PD-1) developed by Shanghai Junshi Bioscience Co., Ltd. Toripalimab is able to bind to PD-1 and block the interaction with its ligands. The binding of toripalimab to PD-1 is mainly attributed to the heavy chain of the former and the FG loop of the latter. Toripalimab received a conditional approval in China for the treatment of melanoma (second-line) in December, 2018. It has also received approvals to treat nasopharyngeal carcinoma (first-line and third-line) and urothelial carcinoma (second-line) in 2021. Additionally, several orphan drug designations were granted to toripalimab by the US Food and Drug Administration. Toripalimab has exhibited primary anti-tumor effects in tumors such as melanoma, lung cancer, digestive tract tumors, hepatobiliary and pancreatic tumors, neuroendocrine neoplasms, nasopharyngeal carcinoma and urothelial carcinoma. It showed a satisfactory anti-tumor effect and long-term survival benefits in Chinese melanoma patients, while the combination of axitinib with toripalimab exhibited an impressive result in metastatic mucosal melanoma. As a checkpoint inhibitor, toripalimab was generally well-tolerated in the enrolled patients. Due to different study populations, comparisons could not be made directly between toripalimab and other drugs in most cases. Nevertheless, the introduction of toripalimab may offer a valuable choice for decision-making in the treatment of tumors in the future.

Efficacy and Safety of the Combination of Nano-Liposomal Irinotecan and 5-Fluorouracil/L-Leucovorin in Unresectable Advanced Pancreatic Cancer: A Real-World Study

Aim: This retrospective study investigated the efficacy and safety of nano-liposomal irinotecan (nal-IRI) plus 5-fluorouracil/l-leucovorin (5-FU/l-LV) treatment in the second-line or later setting for advanced pancreatic cancer under real-world conditions.Methods: Between June 2020 and September 2021, a total of 44 patients with unresectable advanced pancreatic cancer treated with nal-IRI + 5-FU/l-LV in our affiliated hospitals were included. The prognosis, predictive factors (including systemic inflammation-based prognostic indicators), and adverse events were investigated.Results: The median age was 68 (interquartile range [IQR] 62-73) years old, and 22 patients (50.0%) were male. Concerning tumor factors, 9 patients (20.5%) had local advanced disease, and 35 patients (79.5%) had metastases. Twenty-five of the 44 patients were receiving second-line treatment, and 19 were receiving third-line or later treatment. The median overall survival (OS) and progression free survival (PFS) were 9.0 (range, 0.7-15.4) months and 4.4 (range, 0.6-15.4) months, respectively. The overall response rate (ORR) was 5.3%. The disease control rate (DCR) was 44.7%. Patients with a neutrophil-to-lymphocyte ratio (NLR) of >2.7 had a significant risk of a poor OS (HR=0.275, P=0.017). Adverse events were manageable, although gastrointestinal symptoms and neutropenia were observed. The most common grade ≥3 adverse event was neutropenia, which was reported in 20% of patients.Conclusions: Nal-IRI + 5-FU/l-LV therapy was considered to be a useful regimen as second-line or later treatment for unresectable advanced pancreatic cancer, even in clinical practice.

Splenectomy Outcomes in Relapsed or Refractory Immune Thrombocytopenia According to First-Line Intravenous Immunoglobulin Response

Introduction: Although splenectomy has long been second-line option for immune thrombocytopenia (ITP) patients, an indicator that reliably predicts the efficacy of splenectomy is still being explored. We investigated the treatment outcomes of splenectomy as a second-line therapy for relapsed/refractory ITP according to first-line intravenous immunoglobulin (IVIG) responses. Methods: Fifty-two adult patients treated with splenectomy as second-line therapy for ITP between 2009 and 2019 were included, and they were classified according to first-line IVIG responses (no response to IVIG: non-responders; only transient IVIG response shorter than 4 weeks: poor responders; IVIG response for a longer period; stable responders). The efficacy of splenectomy was analyzed in the three subgroups. Results: Of the 52 patients, 10 were IVIG non-responders, 34 were poor responders, and the remaining eight were stable responders. Response to splenectomy was observed in 50.0% of IVIG non-responders, 94.1% of poor responders, and 100% of stable responders (p = 0.0030). Among the 45 patients who responded to splenectomy, 51.1% relapsed subsequently, and a significantly lower relapse rate was noted in the stable IVIG responders (12.5%, p = 0.0220) than in non-responders (60.0%) and poor responders (59.4%). Conclusions: First-line IVIG response is indicated as a useful predictive factor for response to splenectomy.