Two cases of pancytopenia characterized by severe neutropenia induced by anti-PD-1 tislelizumab combined with chemotherapy in non-small cell lung cancer patients and a literature review.

Background: With the increasing use of immune checkpoint inhibitors (ICI) in clinical practice of lung cancer, more immune-related adverse events (irAEs) are being discovered. However, hematologic irAEs (hem-irAEs) were rarely described. Case presentation: Two patients with non-small cell lung cancer were treated with tislelizumab and chemotherapy as the first-line treatment. Immune-related pancytopenia (grade 4 neutropenia, grade 3-4 thrombocytopenia, and grade 3 anemia) occurred after the 3rd (Day 144) and 2nd (Day 32) cycles, respectively. Case 1 had concomitant immune-related hepatitis (grade 3) while Case 2 presented with immune-related mucositis and renal insufficiency (grade 2). Bone marrow examination of Case 1 revealed a hypocellular marrow with increased mature lymphocytes. The patients were given granulocyte-stimulating factor (G-CSF), thrombopoietin, component transfusion (platelet-rich buffy coat and apheresis platelets), and corticosteroids (0.72-1.64 mg/kg/d). Grade 4 neutropenia persisted, with only mild improvements in platelets and red blood cells. Intermittent fever and pulmonary infection were managed with antibacterial and antifungal therapy. Regrettably, both patients died of multiple organ dysfunction syndrome. Naranjo Scale rated tislelizumab-induced pancytopenia as possible in both cases. Conclusion: Although hem-irAEs are rare, they should be distinguished from chemotherapy-induced myelosuppression. Clinicians should remain vigilant, monitor blood cell counts regularly, and intervene promptly to prevent severe complications.