Metabolic pitfall of pseudoprogression after epcoritamab treatment

“Pseudoprogression” is a characteristic phenomenon observed during immunotherapy, including immunomodulatory drugs, immune checkpoint inhibitors, and chimeric antigen receptor T cell (CAR-T) therapy, in which, initially, tumor lesions may appear to worsen, but they subsequently respond favorably. To differentiate between pseudoprogression and true progression, it is essential to assess the pathologic status. However, a biopsy to confirm a pathological diagnosis is not always performed to evaluate the viability of residual lesions because of its invasive procedure. In the recent topic of bispecific T cell engager therapy, epcoritamab, we feel difficulty in estimating treatment efficacy by 18-fluoro-FDG-positron emission tomography (18F-FDG-PET) especially in a case of pseudoprogression. A 62-year-old man with diffuse large B cell lymphoma primarily occurring in bilateral adrenal glands, accompanied by multiple skin lesions, received epcoritamab as forth-line treatment in a recurrence condition after CAR-T therapy. One month after the initial epcoritamab administration, multiple skin lesions regrew. We confirmed an optimal immune response in one of the skin lesions by skin biopsy (Figure 1A), which implied pseudoprogression pathologically. Even after four cycles of epcoritamab therapy, 18F-FDG-PET showed multiple hot spots (maximum standardized uptake values [SUVmax] was 6.03) (Figure 1B) consistent with initial skin lesions. All the skin lesions had been previously documented before epcoritamab therapy. We performed a second skin biopsy, and the pathological complete response was confirmed again (Figure 1C). This suggested that pseudoprogression may manifest as stable metabolic FDG-avid mass even after achieving pathological remission. The patient underwent allogeneic stem cell transplantation while in complete remission following four cycles of epcoritamab therapy. The patient has been still free from therapy for six months post-transplantation. It's important to recognize that 18F-FDG-PET imaging alone is not sufficient for making crucial clinical decisions during immunotherapy. Other factors and assessments should be considered to ensure accurate interpretation and informed decision-making. Nevertheless, the clinical implications of this case suggest that a clinically and metabolically stable mass for months may possibly indicate pseudoprogression rather than true progression. Osamu Imataki managed the patient's case, contributed to the literature search, and wrote the manuscript. Shumpei Uchida and Makiko Uemura made substantial contributions to the concept and design of this report. Osamu Imataki qualified the patient's data. Shumpei Uchida suggested important intellectual content. Osamu Imataki and Makiko Uemura took part in critical discussions. Makiko Uemura was involved in the supervision of the manuscript. Osamu Imataki and Makiko Uemura managed the research. All authors approved the final version of the manuscript. This work was supported by JSPS KAKENHI (Grant Number JP23K11850). The authors declare no conflict of interest. We obtained approval from the Kagawa University Hospital Institutional Review Board (H23-023). This research was conducted ethically following the World Medical Association Declaration of Helsinki. Written informed consent was obtained from the patient for the publication of this study (including the publication of images). The authors have confirmed clinical trial registration is not needed for this submission. All data generated or analyzed during this study are included in this published article. Data are available on reasonable request due to privacy and ethical restrictions.