1154P - Thromboembolic events in patients with melanoma receiving immune checkpoint inhibitors: Incidence and risk factors

Background

Immune checkpoint inhibitors (ICI) improve survival for multiple tumor types, but are possibly associated with thromboembolism (TE). Nonetheless, for patients with melanoma specifically, the risk of TE and its association with treatment setting remain largely unknown. Therefore, we investigated the incidence of TE and associated risk factors in two groups of patients with melanoma who received either palliative or adjuvant ICI therapy between April 2016 and September 2021.

Methods

In this cohort study, baseline characteristics and TE incidences (combined incidence of venous (VTE) and arterial (ATE) thromboembolism) were retrospectively collected from patients with stage III and IV melanoma included in the MULTOMAB trial (NL55840.078.15) until 2 years after the first ICI dose or censoring (switch to alternative anticancer treatment or loss to follow-up). The association between patient characteristics and TE occurrence was analyzed by the Fine-Gray model with backward selection using all-cause death as competing risk.

Results

Out of the 458 included patients, 28 (6%) patients developed a TE during a median follow-up of 17 months, consisting of 18 (4%) VTEs and 10 (2%) ATEs. Median time to TE occurrence was 5.2 months. In the advanced disease (N=315) and adjuvant (N=143) cohort, 23 (7%) and 5 (3%) patients developed TE, respectively. The incidence rates of TE per 100 person years was 4.9 in the total cohort, and 6.4 and 2.4 in respectively the advanced disease and adjuvant cohort. In the advanced disease cohort, BMI (sHR: 1.1 per point BMI increase [95% CI, 1.02 – 1.1, P=0.007]) and nivolumab + ipilimumab combination therapy (sHR 2.5 versus monotherapy [95% CI, 1.08 – 5.6, P = 0.03]) were risk factors for TE occurrence.

Conclusions

In patients with melanoma receiving ICI therapy, TE seems to occur predominantly in patients with advanced disease. In this treatment setting, ICI combination therapy and higher BMI are risk factors for TE. Although this suggests that particularly increased tumor load is a main predisposing factor, possible prothrombotic effects of particularly ICI combination therapy cannot be ruled out. Future research should further study the etiology of TE during ICI therapy while taking disease burden into account.

Clinical trial identification

NL55840.078.15.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

K.D. Joode: Financial Interests, Institutional, Other, Travel expenses by Ipsen - all paid to Institution: Ipsen; Financial Interests, Institutional, Other, Travel expenses by Pamgene - all paid to Institution: Pamgene. A.A.M. Van der Veldt: Financial Interests, Institutional, Other, Consultancy all paid to institute: MSD, Merck, BMS, Pfizer, Eisai, Roche, Sanofi, Novartis, Pierre Fabre, Ipsen. R.H. Mathijssen: Financial Interests, Institutional, Research Grant, Investigator-initiated research: Astellas, Bayer, Cristal Therapeutics, Pfizer, Roche, Sanofi, Servier, Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Coordinating PI: Pamgene. All other authors have declared no conflicts of interest.