Can TTMV clearance predict recurrence in HPV HNSCC?

person Krzysztof Misiukiewicz Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY info_outline Krzysztof Misiukiewicz, Leslie Anne Worona, Emily J Ramos, Richard Lorne Bakst, Kunal K. Sindhu, William Westra, Scott Roof, Eric Michael Genden, Marshall R. Posner

Authors person Krzysztof Misiukiewicz Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY info_outline Krzysztof Misiukiewicz, Leslie Anne Worona, Emily J Ramos, Richard Lorne Bakst, Kunal K. Sindhu, William Westra, Scott Roof, Eric Michael Genden, Marshall R. Posner Organizations Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, Mount Sinai Medical Center, NY, NY, Icahn School of Medicine, New York, NY, Department of Radiation Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, NY, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY Abstract Disclosures Research Funding No funding sources reported Background: Patients with locally advanced (LA) HPV HNSCC are treated with various types of induction chemotherapy (IC) followed by standard (sd) or reduced (rd) chemoradiation (CRT). Tumor tissue-modified viral HPV DNA (TTMV) pairs with PET-CT in predicting an early detection of treatment failure in HPV-related HNSCC. Mid-treatment TTMV assessment in HPV-related HNSCC can help identify patients who are eligible to receive a lower dose of IC and/or CRT or those who may require close follow-up. Methods: Patients with LA HPV+ HNSCC with high-risk features (radiographic ECE, T4 primary, >N2c) and <20 pack-year (py) smoking history were treated with IC followed by rdCRT (56 Gy); sdCRT (70 Gy) was used in non-responders. 16/23 received IC with TPF, 1/23 TP, and 6/23 TP-PD1, and all patients received carboplatin weekly with their CRT. Regeneron trial patients who received TP-Cemiplimab (PD1) IC followed by sdCRT are also continuing adjuvant Cemiplimab alone for 6 months (NCT05376553). PET-CT-confirmed residual, recurrent, or metastatic diseases were defined as treatment failures; TTMV + patients only if PET-CT confirmed. Results: 23 subjects treated with IC followed by CRT between 2/4/21-1/26/24, who had pre- and post-treatment TTMV were included in our analysis. The median pre-IC TTMV was 8082 (27 – 90770). The median follow-up time from treatment start was 21 months. 9/23 patients had full clearance TTMV after 1 cycle of IC defined as rapid responders (RR). 11/23 patients still had positive TTMV after 1 st cycle of IC were defined as slow responders (SR). 1 patient had no TTMV done after 1 cycle of IC but was elevated after 2 nd IC; he was defined as SR. 2 patients had a positive pre-IC TTMV, but no TTMV was drawn during IC to see if RR. 1 of 2 patients was TTMV negative prior to CRT, and 2/2 had a 1 st post IC negative TTMV done 1 week after CRT started. They were both included in the analysis but defined as unknown response status. TTMV testing was done for all 23 subjects after CRT; all were negative. All subjects have TTMV testing done during their surveillance visits. Among 9/23 RR, none developed a failure. Among 12/23 SR, 3 patients developed a failure: 1/3 was TTMV+ but PET-, being followed with TTMV and PET-CT; and 2/3 were confirmed failures, TTMV+ and PET+; 1 locoregional, 1 metastatic. 2 patients were not known to be a SR or RR and had no recurrence. Among 23 patients, NPV of TTMV to detect failure was 100%, but PPV was 96% (1/23). Conclusions: IC followed in rapid clearance of TTMV in 39% of patients, and all remained disease-free. 3/11 (27%) with persistently elevated TTMV after cycle 1 relapsed as of this time point. This small study was not large enough to be practice-changing. However, this is significantly hypothesis-generating and should be tested in a larger trial to help identify patients for de-escalation (RR) or closer surveillance (SR).

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