Pseudoprogression after CAR T-cell therapy mimicking orbital lymphoma relapse

A 50-year-old man with relapsed/refractory diffuse large B-cell lymphoma involving the left orbit and maxillary sinus received chimeric antigen receptor (CAR) T-cell therapy with axicabtagene ciloleucel after lymphodepleting chemotherapy. Prior therapies included immunochemotherapy and radiotherapy, achieving a partial response before CAR T-cell infusion. He developed grade 1 cytokine release syndrome on days 5 and 7, treated with tocilizumab and dexamethasone. On day 12, he complained of painless periorbital swelling. Physical examination revealed a soft, non-tender mass around the left eye (Figure 1A). Magnetic resonance imaging showed a heterogeneously contrast-enhanced mass at the site of prior lymphoma involvement, raising concern for disease relapse. However, diffusion-weighted imaging showed no diffusion restriction, with no corresponding signal decrease on the apparent diffusion coefficient map, suggesting relatively low cellularity (Figure 1B and C).

Figure 1.

(A) Frontal photograph obtained on day 12 after CAR T-cell infusion shows painless left periorbital swelling. Magnetic resonance imaging obtained on the same day shows a heterogeneous ring-enhancing lesion in the left inferior orbit at the site of prior lymphoma involvement (B), while corresponding diffusion-weighted magnetic resonance imaging shows no diffusion restriction within the lesion (C).

This finding contrasted with the initial lymphoma lesion, which had shown marked diffusion restriction on diffusion-weighted imaging. Given the risk of bleeding and infection, a biopsy was deferred. The lesion resolved spontaneously by day 17. ¹⁸F-fluorodeoxyglucose positron emission tomography performed on day 30 confirmed complete metabolic remission.

These findings were consistent with pseudoprogression, a phenomenon observed after immunotherapy, characterized by transient tumour enlargement due to infiltration of immune cells. Pseudoprogression occurs in approximately 5–10% of patients receiving immune checkpoint inhibitors.¹ Although rare, pseudoprogression following CAR T-cell therapy has been reported in lymphoma, with a median onset of 5–7 days (range, 2–21 days).²

Because it closely mimics true progression, pseudoprogression poses a significant diagnostic challenge and may lead to unnecessary investigations or premature changes in treatment. Moreover, local immune-mediated inflammation or compressive effects of the enlarged mass can potentially damage adjacent organs, with life-threatening consequences.³ Awareness among physicians is needed. Physical examination findings and magnetic resonance imaging, particularly the absence of diffusion restriction despite contrast enhancement, may help distinguish pseudoprogression from true progression.

Author contributions

Takashi Miyachi (Conceptualization [equal], Writing—original draft [equal]), Akihiro Kitadate (Conceptualization [equal], Supervision [equal], Writing—original draft [supporting]), and Naoto Takahashi (Writing—review & editing [supporting])

Informed consent

Written informed consent was obtained from the patient for the publication of this case.

Conflict of interest: The authors received no financial or material support from any organization for the submitted work.

Data availability

Additional clinical information is available upon reasonable request.