Durability of response to immune checkpoint inhibitors in metastatic Merkel cell carcinoma after treatment cessation.

Weppler AM, Da Meda L, Pires da Silva I, Xu W, Grignani G, Menzies AM, Carlino MS, Long GV, Lo SN, Nordman I, Steer CB, Lyle M, Trojaniello C, Ascierto PA, Lebbe C, Sandhu S. European Journal of Cancer, (Jan 28 2023), doi:10.1016/j.ejca.2023.01.016


Background: Metastatic Merkel cell carcinoma (mMCC) is highly responsive to immune checkpoint inhibitors (ICIs); however, durability of response after treatment cessation and response to retreatment in the setting of progression is unknown.

Methods: Patients (pts) having mMCC from 10 centres who discontinued ICI treatment for a reason other than progression were studied.

Results: Forty patients were included. Median time on treatment was 13.5 months (range 1-35). Thirty-one patients (77.5%) stopped treatment electively while 9 patients (22.5%) stopped due to treatment-related toxicity. After median of 12.3 months from discontinuation, 14 pts (35%) have progressed (PD). Disease progression rate following ICI discontinuation was 26% (8 of 31) in patients who discontinued in complete response (CR), 57% (4 of 7) in patients in partial response and 100% (2 of 2) in those with stable disease. Median progression-free survival (PFS) after treatment cessation was 21 months (95% confidence interval [CI], 18- not reached [NR]), with a third of patients progressing during their first year off treatment. PFS was longer for patients who discontinued ICI electively (median PFS 29 months; 95% CI, 21-NR) compared to those who stopped due to toxicity (median PFS 11 months; 95% CI, 10-NR). ICI was restarted in 8 of 14 pts (57%) with PD, with response rate of 75% (4 CR, 2 partial response, 1 stable disease, 1 PD).

Conclusion: ICI responses in mMCC do not appear durable off treatment, including in patients who achieve a CR, though response to retreatment is promising. Extended duration of treatment needs to be investigated to optimise long-term outcomes.