Grade ≥ 3 hematologic adverse events of immunotherapy in advanced NSCLC patients: a systematic review and meta-analysis.

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The impact of incorporating immune checkpoint inhibitors (ICIs) into standard chemotherapy on the severity and risk of myelosuppression in advanced non-small cell lung cancer (NSCLC) patients remains uncertain. We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) that evaluated ICIs in people with NSCLC. A comprehensive search of four databases, PubMed, Web of Science, Embase, and the Cochrane Library, was carried out from inception to 30 October 2023. Pooled analyses assessed the risk ratios (RR) for treatment-related hematological adverse events greater than or equal to grade 3. The protocol is registered with PROSPERO and has the CRD42024500056 registration number. Twenty-three phase 3 RCTs were contained, involving 15,844 people with NSCLC receiving ICIs with or without chemotherapy. Compared with chemotherapy alone, ICI monotherapy or dual immunotherapy reduced treatment-associated leukopenia (relative risk (RR) 0.03, 95% CI 0.01-0.08), neutropenia (RR 0.02, 95% CI 0.01-0.03), thrombocytopenia (RR 0.05, 95% CI 0.02-0.14), and anemia (RR 0.09, 95% CI 0.05-0.15), with a pooled incidence of 0.07%, 0.08%, 0.14%, and 9.07%. Compared with chemotherapy alone, ICIs in combination with chemotherapy increased the risk of developing treatment-related thrombocytopenia (RR 1.35, 95% CI 1.04-1.77), with a pooled incidence rate of 6.83%; it did not increase leukopenia (RR 0.97, 95% CI 0.70-1.35), neutropenia (RR 1.05, 95% CI 0.90-1.23), and anemia (RR 1.10, 95% CI 0.85-1.43), with pooled incidence rates of 4.47%, 14.67%, and 13.36%, respectively. For patients with advanced or metastatic NSCLC, severe hematological adverse events are uncommon when ICIs are used alone, as opposed to chemotherapy. However, when used in conjunction with chemotherapy, these side effects may be intensified, particularly in the form of an elevated incidence of thrombocytopenia of grade 3 or higher.