Abstract P010

Clinico-pathological correlation in patients with positive end of treatment PET after pembrolizumab + AVD for untreated classic Hodgkin lymphoma

Background: Concurrent pembrolizumab with AVD chemotherapy is highly effective in the treatment of classic Hodgkin lymphoma (CHL) (Lynch et al. ASH 2023). However, this regimen and similar regimens have been associated with higher rates of residual PET positivity (PET2 CR = 61%, EOT CR = 77%) despite extremely low rates of biopsy-proven disease progression (Advani et al. ASH 2023). Additional characterization of the long-term outcomes of these patients may identify characteristics not associated with persistent lymphoma.

Methods: We examined the outcomes of patients treated with pembrolizumab + AVD (NCT03331341) who had partial metabolic response on end-of-treatment (EOT) F-18 fluorodeoxyglucose (FDG) PET. With this information, we performed a post-hoc descriptive analysis landmarked at the time of the EOT PET. In patients who had a biopsy as part of this workup, a secondary hematopathology and radiology overread was requested with additional clinical context.

Results: Among 50 patients treated in this study, 48 were evaluable with an EOT PET after completion of all therapy. Twelve (25%) had residual FDG uptake (D4 or D5) on the EOT PET. Seven (58%) patients with positive PET findings had at least one biopsy to evaluate for recurrence, of whom only one had a biopsy-proven CHL recurrence at any time.

We evaluated the eight negative biopsies. One biopsy showed normal lung tissue, but a subsequent cecal biopsy in the same patient at a new site showed diffuse large B-cell lymphoma. Two patients had biopsies that showed benign adipose tissue, one with a hyperplastic thymus, and one with inadequate sample.

Two patients had biopsies that demonstrated areas of necrosis surrounded by a histiocytic reaction. Interestingly, these pathology findings correlated with PET results that showed central necrosis with photopenia with a thin rim of peripherally intense FDG uptake at an original site of disease. In reviewing the other 5 patients who did not have any subsequent biopsy, we found one other patient also had this pattern. Other PET findings not associated with eventual recurrence included mild cervical lymph node FDG uptake (n=5) and thymic FDG uptake (n=3). Additional details are present in the figure below.

Conclusions: Partial metabolic response with persistent small-volume FDG positive disease on EOT PET after pembrolizumab + AVD is not associated with high rates of disease relapse. Patients can be safely followed with serial imaging and/or biopsy.