1932P - Tyrosine kinase inhibitors-induced erythrocytosis in thyroid cancers: A novel safety signal from a retrospective study

Background

Tyrosine kinase inhibitors (TKIs) are the most effective systemic therapies in thyroid cancers (TC). Safety management is crucial for maintaining treatment adherence. Among hematological toxicities, anemia is mostly reported, while TKIs-induced erythrocytosis (TIE) has been rarely assessed in TC.

Methods

A retrospective study was conducted across 2 Italian centers to describe TIE incidence and management upon TKIs in any TC histotype. We reviewed TC patients (pts) treated between 2012-2023 with TKIs: lenvatinib (L), cabozantinib (C), vandetanib (V), sorafenib (S), RET-inhibitors (RETi) (selpercatinib, pralsetinib) and BRAFi+MEKi (dabrafenib+trametinib). As TIE is not included in CTCAE, it was defined according to WHO criteria (PMID: 27069254).

Results

At a median follow-up of 68.5 months (mo), 135 pts were analyzed. TIE occurred in 24 pts (17.8%). Out of them, 16 pts (66.6%) had >1 TIE event (14/16 pts upon the same TKI) accounting for 50 events totally. Hemoglobin (Hb) and hematocrit (Hct) median values were similar at 1^st, 2^nd, 3^rd TIE relapse [16.9/51.9, 16.8/52.7, 16.7/51.5 Hb(mg/dL)/Hct(%), respectively]. RETi were the drug class with the highest Hb/Hct median values (18.2/54.9) at first TIE onset, and the highest TIE incidence [7/15 (46.7%) events compared to 2/22 (9.1%), 11/73 (15.1%), 6/29 (20.7%), 0/7, 0/28 events occurred on C, L, V, S, and BRAFi+MEKi, respectively, Fisher’s Exact test, p=0.002]. The median time to first TIE was 1.3 mo: later with L (2.9 mo) and earlier with C/V/RETi (0.6/0.8/0.9 mo, respectively) (log-rank test, p=0.015). In 32 events, TKIs were temporarily discontinued and in 9 phlebotomy was performed. No TIE was related to JAK2 gene mutations and abnormal erythropoietin. TIE was not associated to TKIs response (TKIr) (Fisher’s Exact test, p=0.212) and progression-free survival (PFS) (log-rank test, p=0.169).

Conclusions

Our study first revealed a not negligible TIE incidence (17.8%), most frequently with RETi. TIE is an early adverse event, which tends to recur without increasing in severity (Hb/Hct values). TIE was not associated with oncologic outcomes (TKIr, PFS). Further studies needed to elucidate TIE mechanisms, management, and association with cardio-vascular events.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Cavalieri: Financial Interests, Institutional, Speaker’s Bureau: AccMed; Financial Interests, Institutional, Sponsor/Funding: AccMed, MultiMed, Engineers srl, Care Insight sas. B. Paolini: Financial Interests, Institutional, Advisory Board: Eisai. L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics, GSK; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Adlai Nortye. L.D. Locati: Financial Interests, Institutional, Advisory Board: Eisai, MSD, Merck Serono, Eli Lilly, Sanofi, Sunpharma, Ipsen, Bayer, Roche, Istituto Gentili Srl, New Bridge, Seagen, Novartis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Gilead; Non-Financial Interests, Personal and Institutional, Member of Board of Directors: ESMO Task Force for Thyroid Cancer and Salivary Gland Cancer Guidelines, EORTC Endocrine Task Force and Head & Neck group; Non-Financial Interests, Personal and Institutional, Leadership Role: Coordinator of the Italian Medical Oncology Association (AIOM) Guidelines in Thyroid Cancers. S. Alfieri: Financial Interests, Institutional, Advisory Board: Eisai. All other authors have declared no conflicts of interest.