Single dose of rituximab causing organising pneumonia in a patient with B-cell lymphoproliferative disorder

Background

Rituximab (RTX) is a chimeric anti-CD20 monoclonal antibody used to treat CD20+non-Hodgkin's lymphoma. RTX has been reported to cause both hypersensitivity pneumonitis and OP.1 The incidence of RTX-organising pneumonia (RTX-OP) has been increasingly recognised.

Case presentation

A 49-year-old woman with underlying cold agglutinin disease presented with recurrent haemolytic anaemia despite adequate steroid therapy. She underwent a bone marrow aspiration and trephine biopsy, which confirmed the diagnosis of CD5-negative B-cell lymphoproliferative disorder. She was planned for RTX, fludarabine and cyclophosphamide as initial induction therapy. At baseline, she was not on any other chemotherapy agents.

She received her first dose of intravenous RTX 500 mg (375 mg/m²) infused over 6 hours with no immediate complications. Three days following the first dose of RTX, she developed high-grade fever, non-productive cough and dyspnoea. Clinical examination showed a temperature of 39°C, pulse rate of 110 bpm, blood pressure of 110/68 mm Hg and oxygen saturation of 82% on room air. Auscultation of the lungs revealed crepitations in both lower zones. Chest radiograph showed bilateral pulmonary infiltrates. Laboratory investigations showed: total white cell count 16.8×10⁹/ L (neutrophil 83.6%), serum C reactive protein 5.08 mg/dL, serum procalcitonin of 0.37 ng/mL and arterial blood gas showed hypoxic respiratory failure with pH 7.40, pO₂ 52 mm Hg, pCO₂ 24.7 mm Hg and bicarbonate of 24 mmol/L. She was initiated on oxygen therapy as well as broad-spectrum antibiotics for hospital-acquired pneumonia. Sputum for cultures, acid-fast bacilli direct smear, mycobacterium PCR was all negative. Sputum eosinophil counts were normal. Given the immunosuppressed status of the patient, workup for respiratory viral pathogen real-time PCR assays for Pneumocystic Jiroveci, Cytomegalovirus and SARS-CoV-2 was done and they were negative.

She showed poor clinical and radiological response prompting further investigations. A high-resolution CT (HRCT) of the chest showed bilateral ground-glass opacities (GGO) with interlobular septal thickening and arcade-like signs suggestive of OP (figure 1A,B). Trans-bronchial lung biopsy was planned but could not be performed as she deteriorated and required NIV (bi-level positive airway pressure) ventilation. A diagnosis RTX-OP was made and she was treated with IV methylprednisolone (MTP) 500 mg/day for 5 days. There was a rapid improvement of her symptoms and she was weaned off the ventilatory support in 1 week. Spirometry performed was consistent with a restrictive ventilatory defect with the FVC of 1.76 L (66% predicted) and a moderate reduction of diffusing capacity of lungs for carbon monoxide (60%). She was continued on maintenance oral prednisolone at a dose of 1 mg/kg body weight for 6 weeks followed by gradual tapering of 0.25 mg/kg bodyweight every 2 weeks.

Outcome and follow-up

On review in the clinic at 6 weeks, the oxygen saturation was 98% on room air and the chest was clear on auscultation. A repeat HRCT chest showed complete resolution of the GGO (figure 1C,D). Due to the limited safety data on RTX-induced lung injury and the possibility of a more severe second reaction, our patient was not rechallenged with RTX. She was planned for obinutuzumab as the treatment regime.