Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis.

Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present systematic review and meta-analysis, we sought for assessing the efficacy and safety of Immune checkpoint inhibitors (ICIs) in patients with prostate cancer. PubMed, Scopus, Web of Science, and EMBASE databases were searched on Aguste 19, 2022. Thirty five studies met the eligibility criteria. The median overall survival (mOS) of all treatments was 14.1 months, with the longest and shortest mOS was seen among patients who received anti-CTLA-4 monotherapy and anti-PD-1/PD-L1+anti-CTLA-4 regimen at 24.9 and 9.2 months, respectively. Noteworthy, all types of adverse events had the lowest incidence in the anti-PD-1/PD-L1 monotherapy group. Considering the ICI monotherapy regimens, we found that fatigue, diarrhea, and infusion reaction had the highest incidence rates. Future studies evaluating the efficacy and safety of novel combination therapies with ICIs are warranted.

Validation of Persian Multiple Sclerosis quality of life-29 (P-MSQOL-29) questionnaire.

BACKGROUND: Multiple sclerosis (MS) is the most prevalent neurological disease among young adults. Because of the chronic nature of this disease, it is important to assess quality of life in these patients. The Multiple Sclerosis Quality of Life -29 (MSQOL-29) questionnaire which contains two main scales, Physical Health Composite (PHC) and Mental Health Composite (MHC), has been designed for this goal. The purpose of the present study is to translate and validate a Persian version of MSQOL-29 (P-MSQOL-29). METHODS: Using the forward-backward translation method, a panel of experts established the content validity of P-MSQOL-29. It was then administered to 100 patients with MS who also completed the Short Form-12 (SF-12) questionnaire. Cronbach's alpha was used to assess the internal consistency of P-MSQOL-29. Spearman's correlation coefficient was used to analyze the concurrent validity when correlating the items of P-MSQOL-29 to SF-12. RESULTS: Mean (Standard Deviation) of PHC and MHC for all patients was 51 (16.4), and 58 (23), respectively. Cronbach's alpha was 0.7 for PHC and 0.9 for MHC. Thirty patients completed the questionnaire again after 3-4 weeks, Intraclass Correlation Coeffiecient (ICC) was 0.80 for PHCs and 0.85 for MHCs (both P values < 0.01). A moderate to high correlation was detected between MHC/PHC and the corresponding scales of SF-12 (MHC with Mental Component Score: ρ = 0.55; PHC with Physical Component Score: ρ = 0.77; both P values < 0.01). CONCLUSION: P-MSQOL-29 is a valid and reliable questionnaire and can be used for assessing quality of life in patients with MS.

Immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric and esophageal cancers: A systematic review and meta-analysis.

BACKGROUND: Esophageal, gastroesophageal, and gastric cancers are still among the leading causes of death worldwide. The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment strategy for several cancers. The combination of conventional chemotherapy with ICIs has been hypostatized to play a synergic effect over the chemotherapy alone regimen. Thus, the present systematic review and meta-analysis was conducted to compare the efficacy and safety of ICIs plus chemotherapy versus chemotherapy alone in patients suffering from advanced esophageal, gastroesophageal, and gastric cancers. METHODS: PubMed, Scopus, Web of Science, and EMBASE databases together with the conference abstracts of ASCO and ESMO were searched systematically up to March 25, 2022. The studies were selected in two steps, title/abstract and full-text screening. The primary outcome was set at the efficacy of ICIs plus chemotherapy relative to the chemotherapy alone in terms of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The secondary outcome was the safety in terms of treatment-related adverse events (TRAEs) and immune-related AEs. RESULTS: A total of 11 publications involving 6,732 patients were included. First-line ICIs plus chemotherapy showed superior effect over chemotherapy alone in terms of OS (hazard ratio [HR] 0.76, 95 %CI 0.72-0.81), PFS (HR 0.68, 95 %CI 0.61-0.75), ORR (risk ratio [RR] 1.29, 95 %CI 1.20-1.40), and DCR (RR 1.06, 95 %CI 1.03-1.09). Significant predictors of OS benefit in combination therapy versus chemotherapy alone were PDL-1 combined positive score (CPS) ≥ 10 compared to CPS < 10 (p = 0.012), tumor proportion score (TPS) ≥ 1 % compared to TPS < 1 % (p = 0.016), and male gender compared to the females (p = 0.024). In the safety analysis, ICIs plus chemotherapy showed a higher rate of TRAEs in terms of any grade AEs (RR 1.02, 95 %CI 1.00-1.04), grade ≥ 3 AEs (RR 1.16, 95 %CI 1.06-1.26), serious AEs (RR 1.63, 95 %CI 1.44-1.85), and AEs led to treatment discontinuation (RR 1.51, 95 %CI 1.37-1.67). Furthermore, the rate of immune-related AEs of any grade (RR 2.18, 95 %CI 1.55-3.05) and immune-related grade ≥ 3 AEs (RR 2.76, 95 %CI 1.85-4.13) were also higher in ICI combination therapy group relative to chemotherapy alone group. CONCLUSION: Our findings demonstrated that first-line ICIs plus chemotherapy versus chemotherapy alone prolonged OS and PFS in patients with advanced esophagogastric cancers. Also, the rate of AEs was remarkably higher in the combination group. As a result, identifying methods to prevent AEs without affecting the efficacy of ICIs is highly warranted.

A systematic review and meta-analysis of immune response against first and second doses of SARS-CoV-2 vaccines in adult patients with hematological malignancies.

BACKGROUND: Cancer patients particularly those with hematological malignancies are at higher risk of affecting by severe coronavirus disease 2019 (COVID-19). Due to the immunocompromised nature of the disease and the immunosuppressive treatments, they are more likely to develop less antibody protection; therefore, we aimed to evaluate the immunogenicity of COVID-19 vaccines in patients with hematological malignancies. METHODS: A comprehensive systematic search was conducted in PubMed, Scopus, and Web of Science databases, as well as Google scholar search engine as of December 10, 2021. Our primary outcomes of interest comprised of estimating the antibody seropositive rate following COVID-19 vaccination in patients with hematological malignancies and to compare it with those who were affected by solid tumors or healthy subjects. The secondary outcomes were to assess the vaccine's immunogenicity based on different treatments, status of the disease, and type of vaccine. After the two-step screening, the data were extracted and the summary measures were calculated using a random-effect model. RESULTS: A total of 82 articles recording 13,804 patients with a diagnosis of malignancy were included in the present review. The seropositive rates in patients with hematological malignancies after first and second vaccine doses were 30.0% (95% confidence interval (95%CI): 11.9-52.0) and 62.3% (95%CI 56.0-68.5), respectively. These patients were less likely to develop antibody response as compared to cases with solid tumors (RR 0.73, 95%CI 0.67-0.79) and healthy subjects (RR 0.62, 95%CI 0.54-0.71) following complete immunization. Chronic lymphocytic leukemia (CLL) patients had the lowest response rate among all subtypes of hematological malignancies (first dose: 22.0%, 95%CI 13.5-31.8 and second dose: 47.8%, 95%CI 41.2-54.4). Besides, anti-CD20 therapies (5.7%, 95%CI 2.0-10.6) and bruton's tyrosine kinase inhibitors (26.8%, 95%CI 16.9-37.8) represented the lowest seropositiveness post first and second doses, respectively. Notably, patients who were in active status of disease showed lower antibody detection rate compared to those on remission status (RR 0.87, 95%CI 0.76-0.99). Furthermore, lower rate of seropositivity was found in patients received BNT162.b2 compared to ones who received mRNA-1273 (RR 0.89, 95%CI 0.79-0.99). CONCLUSION: Our findings highlight the substantially low rate of seroprotection in patients with hematological malignancies with a wide range of rates among disease subgroups and different treatments; further highlighting the fact that booster doses might be acquired for these patients to improve immunity against SARS-CoV-2.