B cell-driven refractory hemocytopenia in immune checkpoint inhibitor therapy: a report of two cases

The integration of immune checkpoint inhibitors (ICIs) with chemotherapy has revolutionized lung cancer treatment, yet it amplifies the risk of severe hematologic toxicities.

We describe two patients with advanced lung cancer who developed life-threatening refractory hemocytopenia following ICIs-chemotherapy, unresponsive to glucocorticoids and hematopoietic growth factors. A striking feature of these cases was the exclusive presence of anti-Sjögren's-syndrome-related antigen A (Ro) (SSA) antibodies in refractory patients, but absent in non-refractory controls. Targeted administration of intravenous immunoglobulin (IVIG) and rituximab was temporally associated with clearance of anti-SSA antibodies and restoration of normal hematopoiesis, raising the hypothesis that aberrant B cell activity may contribute to refractory hemocytopenia in this setting.

These observations suggest that anti-SSA antibodies could represent a candidate biomarker for identifying refractory hemocytopenia in early time. These findings support a proposal for routine anti-SSA screening in ICI-related hematologic toxicity to enable timely B cell-targeted management.