Old Pathogens-New Patient Types: Infections in a CAR T-Cell Recipient. Could It Get Any More Complicated?

Abstract

The case discussed involves a 41-year-old Italian man who was a candidate for chimeric antigen receptor T-cell therapy (CAR-T) for mediastinal diffuse large B-cell lymphoma. His CAR-T treatment was postponed several times due to prolonged relapsing COVID-19 and new onset of pulmonary Mycobacterium tuberculosis diseases. After 11 weeks of antimycobacterial treatment, CAR T-cell therapy was performed, but complicated by cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Two months after CAR-T, the patient developed invasive pulmonary aspergillosis due to A. fumigatus. He was successfully treated with a 6-month course of antitubercular therapy and an 8-month course of antifungal therapy with isavuconazole. Lobectomy was performed due to episodes of severe hemoptysis. The challenging issues of diagnosis, choice, and management of treatments, including drug-drug interactions and length of therapy, are discussed.

FIGURE 1

Clinical timeline, shown in months from time 0, defined as the date of CAR‐T treatment indication. Asterisks represent times when radiologic re‐evaluation with CT or PET scan was performed. BAL, bronchoalveolar lavage; CAR‐T, Chimeric Antigen Receptor T‐cell; moxiH, moxifloxacin, isoniazid; R‐DA‐EPOCH, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride, and rituximab; R—DHAOX, rituximab, dexamethasone, high‐dose cytarabine, and oxaliplatin; RHZE rifampicin, isoniazid, pyrazinamide, ethambutol; RH, rifampicin, isoniazid; RT, radiotherapy.

FIGURE 2

CT scan showing the mediastinal mass of DLBCL before (a), during (b), and after first‐line (c) and second‐line (d) chemotherapy. The lesion was in the mediastinum, but as it was very close to the upper left lobe, on imaging it was not always very clear if the lung was involved or not.

FIGURE 3

At 1 (+1) and 2 (+2) months after COVID‐19 diagnosis (concomitant with indication for CAR‐T therapy, time 0), the CT scan did not show any typical signs of COVID‐19 pneumonia. However, new lesions with a tree‐in‐bud shape (arrows), not present in previous scans, appeared and were confirmed at the following scan.

FIGURE 4

Upper panel: CT scan, performed after nearly 11 weeks of antitubercular therapy: a radiological progression of lymphoma and TB lesions is shown, with the appearance of excavations. CAR T‐cell therapy was administered 2 weeks later. Lower panel: 1 month after CAR‐T the CT scan showed an evolution in the radiological findings: the lesion where the lymphoma used to be increased in volume, mainly excavated component, which could be an effect of CAR T‐cell therapy. The TB lesion became more consolidated.

FIGURE 5

Upper panel: PET scan performed 1 month after stopping antitubercular treatment (Month +11) showed a slight metabolic increase compared with previous controls at the level of the left anterior lung lesion (arrows). Pulmonary lobectomy performed 2 weeks later (at Month +11.5) due to clinical worsening with extensive hemoptysis. Lower panel: PET scan performed after pulmonary lobectomy showed a residual uptake, due to either recent surgery or residual fungal infection. A PET scan performed almost 2 years after CAR‐T (Month +32) did not show any sign of infection or hematologic disease.