ABSTRACT
Ziel/Aim The global SARS-CoV-2 vaccination campaign brought attention to a recent pitfall in tumor staging by PET/CT. Several publications reported a non-specific F-18-FDG tracer uptake in axillary lymph nodes after COVID-19 vaccination. Ga-68-FAPI PET/CT is a new oncologic imaging tool that may overcome this limitation. Methodik/Methods For this purpose, we compared the tracer uptake in a head-to-head and same-day F-18-FDG and Ga-68-FAPI PET/CT study. 11 patients from our prospective database (NCT04571086) were included showing vaccine-related tracer uptake in axillary lymph nodes up to 6 weeks after COVID- 19 vaccination. Ergebnisse/Results Among the total of 11 patients, all (n = 11) showed visual positive uptake in the lymph nodes ipsilateral to the injection side on F-18-FDG PET. None (n = 0) of the included patients showed significant tracer uptake on Ga-68-FAPI PET. Follow-up imaging confirmed reactive nodal uptake in all patients. The tumor detection efficacy for these patients was 73 % for F-18-FDG and 94 % for Ga-68-FAPI. Schlussfolgerungen/Conclusions In our case series, Ga-68-FAPI demonstrated resistance to vaccine-related pitfalls while presenting superior tumor detection.
ABSTRACT
Background: Anti-CD22 recombinant immunotoxin moxetumomab pasudotox (Moxe) is FDA-approved for hairy cell leukemia (HCL) patients who have received at least two prior systemic therapies including a purine nucleoside analog. In phase 3 testing the complete remission (CR) rate was 41%, and response was higher in patients with lower tumor burden and lower titers of antidrug antibodies (ADA). Phase 1 testing indicated that most CRs were without minimal residual disease (MRD) and eradication of MRD was associated with prolonged CR duration. Monoclonal antibody (Mab) rituximab binds to CD20 on HCL cells and induces apoptosis or immune-mediated killing, but as a single-agent achieved only 13% CRs in relapsed HCL requiring therapy. In a phase 1 trial to determine safety, rituximab was combined with Moxe, with the goal to help reduce tumor burden and to prevent or delay ADA by killing normal B-cells. Methods: To allow rituximab sufficient time to accomplish both goals, it was infused 3 days before day 1 of cycle 1 at 375 mg/m2 , and Moxe was given by 30-minute infusion on days 1, 3 and 5. On repeat cycles of Moxe days 1, 3 and 5, rituximab was given on day 1. Cycles were generally spaced 4 weeks apart. Moxe was begun at a lower dose, 30 rather than the 40 mcg/kg dose used in phase 3 in case the rituximab would increase its toxicity. Bone marrow aspirate flow cytometry, which can detect 0.002% HCL cells, was the most sensitive test used for MRD detection, much more sensitive than BRAF V600E digital droplet PCR (ddPCR) or bone marrow biopsy immunohistochemistry (IHC). Patients could receive 4 cycles past MRD-free CR, but not more than 8 cycles. Results: Three patients received Moxe at 30 mcg/Kg/dose and 6 received 40 mcg/Kg/dose, all without dose limiting toxicity (DLT). There was no evidence of hemolytic uremic syndrome or capillary leak syndrome. To prevent intravascular hypovolemia due to expected third spacing, patients were encouraged to drink one cup per hour of water or other fluid from days 1 to 8 and take dexamethasone 4 mg orally if headache or nausea prevented good oral hydration. Of the 9 patients, 7 (78%) achieved CR after 2 (n = 6) or 3 (n = 1) cycles, and achieved MRD-free CR after 2 (n = 3), 4 (n = 3) or 6 (n = 1) cycles. No patients became infected with COVID-19. Conclusions: This phase 1 trial met its primary endpoint of determining whether rituximab could be safely combined with Moxe and will enroll 4 additional patients to further access clinical activity. Further testing will determine whether addition of a CD20 Mab to Moxe significantly improves clinical outcome compared to Moxe alone, particularly long-term MRD-free CR rate.