Pembrolizumab and reactivation of TB: is there a link?

Pembrolizumab and reactivation of TB: is there a link?Immune checkpoint inhibitors (ICIs), particularly programmed cell death protein 1 (PD-1) inhibitors such as pembrolizumab, have transformed cancer treatment by enhancing anti-tumour immunity.However, immune activation may also disrupt TB infection (TBI) control, leading to reactivation, especially in TB-endemic regions.The immunopathology of TB reactivation is a complex phenomenon.Diagnosis is challenging because TB can mimic disease progression or immune-related inflammation on imaging.We present three cases of TB occurring during pembrolizumab therapy, highlighting diagnostic dilemmas and the importance of early microbiological evaluation and prompt anti-tubercular therapy (ATT) -see Table. CASE 1A 76-year-old man with a known history of hypertension presented with left flank pain, flank fullness, and significant weight loss of 7 kg over 3 months.He had no past history of TB or TB contact exposure.He was diagnosed with clear cell renal cell carcinoma (pT3c) and subsequently underwent radical nephrectomy, followed by adjuvant therapy with pembrolizumab.After completing eight cycles over 6 months, positron emission tomography combined with computed tomography (PET-CT) revealed pleural thickening, pleural effusion, and mediastinal lymphadenopathy, which were initially interpreted as disease progression, and hence pembrolizumab was continued (Figure).After receiving a total of 12 cycles of pembrolizumab over 9 months, imaging demonstrated improvement in pleural disease, but new lung nodules appeared.Subsequently, the patient developed a fever, weight loss, an acute confusional state, and respiratory compromise.High-resolution CT chest revealed cavitatory consolidation and multiple pulmonary nodules suggestive of TB.Bronchoalveolar lavage was 3þ positive for acid-fast bacilli and Gen-eXpert MTB, confirming pulmonary TB.ATT was initiated, resulting in rapid clinical improvement.