Cardiotoxicity with Immune System Targeting Drugs: A Meta-Analysis of Anti-PD/PD-L1 Immunotherapy Randomized Clinical Trials

Abstract

Background: With antiprogrammed death receptor-1 (anti-PD-L1) therapy, a recent meta-analysis reported higher incidence of cutaneous, endocrine and gastrointestinal complications especially with dual anti-PD-L1 immunotherapy (IMM). Methods: Our primary outcome was assessment of all cardiotoxicity grades in IMM compared with different treatments, thus a systemic review and a meta-analysis on randomized clinical trials (RCTs) were done. Results: We included 11 RCTs with 6574 patients (3234 patients in IMM arm vs 3340 patients in the other arm). Three non-small-cell lung cancer RCTs, seven melanoma RCTs and only one prostatic cancer RCT met the inclusion criteria. There were five RCTs that compared monoimmunotherapy to chemotherapy "(n = 2631 patients)". No difference exists in all cardiotoxicity grades or high-grade cardiotoxicity (p > 0.05). Lung cancer exhibited a higher response rate and lower mortality in IMM. Conclusion: There was no reported statistically significant cardiotoxicity associated with anti-PD/PD-L1 use. Lung cancer subgroups showed better response and survival rates.

Exosomes as a Surrogate Marker for Autophagy in Peripheral Blood, Correlative Data from Phase I Study of Chloroquine in Combination with Carboplatin/Gemcitabine in Advanced Solid Tumors

“…And it has been implicated in evading immune surveillance (Janji et al, 2016). Thus, can be related to various predictive and prognostic markers Abdel Karim et al, 2018;Magdy et al, 2018Rahouma et al, 2019). However, these studies have always been in vitro experiments or done using murine models.…”

Adverse cardiac events in the treatment of non-small cell lung cancer with programmed death-1and programmed death-ligand 1 inhibitors

“…The mechanism of PD-1 and PD-L1 inhibitors involves mainly restarting the T cell-mediated tumor cell death process; at the same time, interferes with the normal immune system. In a meta-analysis, the authors divided patients into NSCLC group and other cancer groups (melanoma, prostate cancer), that is, based on the cancer types and indicated that PD-1/PD-L1 inhibitors have no significant differences in cardiotoxicity compared with chemotherapy or placebo [ 25 ] . However, since the search date was limited to February 2017, only 3 studies of NSCLC were included.…”

“…In the most recent meta-analysis, the findings showed no marked differences in cardiotoxicity between immunotherapy and chemotherapy. [ 25 ] This is because individual adverse cardiac events were not analyzed, and only 3 clinical trials were included with the retrieval date set for February 2017. In recent years, several clinical trials have been conducted and results published in peer-reviewed journals.…”

How to Monitor Cardiac Complications of Immune Checkpoint Inhibitor Therapy

“…Nevertheless, it is again worth to underline that in the absence of a structured programme of cardio-oncologic vigilance, the great majority of myocarditis events may be overlooked, or misdiagnosed. A recent meta-analysis of randomized clinical trials found that without a proactive surveillance it is not possible to detect significant cardiotoxicity associated with use of anti-PD-1/PD-L1 immunotherapy ( Rahouma et al., 2019 ). The clinical trial reporting system, yet burdened by sometimes-misleading definitions, also strongly relies on investigator judgment for reporting adverse events.…”