Real-World Survival in Patients with Metastatic Melanoma after Discontinuation of Anti-PD-1 Immunotherapy for Objective Response or Adverse Effects: A Retrospective Study

Abstract

Objective. Anti-PD-1 has dramatically improved the survival of patients with advanced melanoma. However, there is a lack of data on maintenance of the response after treatment discontinuation. We aimed to evaluate the progression-free survival (PFS) of patients with metastatic melanoma after anti-PD-1 interruption for objective response (OR) or limiting toxicity during clinical trials. Methods. All patients with advanced melanoma who stopped single-agent anti-PD-1 antibodies for objective response or toxicity were included between April 2014 and January 2019 in our institution (data cut-off, September 10th, 2019). Clinical and biological factors associated with relapse were studied. Results. The median follow-up after introduction of treatment was 36.5 months [4.6–62.4], and the median follow-up after discontinuation of treatment was 15.7 months (2.5–45.1). Out of 65 patients, 28 patients stopped immunotherapy for limiting adverse effects (AEs) (43.1%), 25 for complete response (CR) (38.4%), and 12 for partial response (PR) or long-term stable disease (SD) (18.5%). Twelve patients relapsed (18.5%) after a median time of 9 months [1.9–40.9 months]. Seven relapsed after discontinuation for AEs, 3 after discontinuation for CR, and 2 after discontinuation for PR/SD. The median PFS after therapy discontinuation was not reached. No statistical association was found between recurrence and age, sex, increased LDH, BRAF status, presence of brain metastases, previous treatments, radiotherapy, or time on anti-PD-1 treatment. Conclusion. This cohort shows a global recurrence rate of 18.5% and confirms a long-lasting response after anti-PD-1 cessation regardless of the cause of discontinuation.

Prognoses of patients with melanoma who continue/discontinue anti-programmed death-1 therapy after achieving a complete response in a real-world setting: a multicentre retrospective study

“…In our study, the median time to relapse after discontinuation was 9 months, which is comparable with previous reports (8·0–12·0 months) 2,3,5,6 . Based on these results, careful follow‐up is required for the first year after the treatment discontinuation.…”

“…also reported two (15%) relapses among 13 patients who achieved a CR, 4 and Valentin et al . observed three (12%) patients among 25 who achieved a CR after a median time after anti‐PD‐1 discontinuation of 22·3 months 5 . Asher et al .…”

“…Dear Editor , It is not known how long anti‐programmed death‐1 (anti‐PD‐1) therapy should be continued for patients with melanoma who have achieved a good response. Only a few studies have investigated this topic, and most did not include acral or mucosal melanomas 1–6 . We retrospectively analysed 57 patients with advanced melanoma (including 12 patients with unresectable lymph node involvement) treated with anti‐PD‐1 monotherapy who achieved a complete response (CR) from 16 collaborating institutions treated during the period from 1 September 2014 to 31 July 2019.…”

What is the optimal duration of immune checkpoint inhibitors in malignant tumors?

“…It has been shown that when the active disease is not detected on CT or PET/CT scans or biopsies, discontinuing anti-PD-1 therapy after 12 months may result in a lower rate of disease recurrence in patients with advanced melanoma ( 50 ). In a retrospective study by Valentin et al., patients with advanced melanoma who discontinued anti-PD-1 therapy for reasons other than disease progression were shown to have durable responses with a disease recurrence rate of only 18.5% ( 51 ). A real-world multicentric observational study including 1011 patients in India showed that short-course ICIs therapy had comparable efficacy/safety to standard ICIs therapy ( 52 ).…”

Predictive Biomarkers of Severe Immune-Related Adverse Events With Immune Checkpoint Inhibitors: Prevention, Underlying Causes, Intensity, and Consequences

“…Other immunomodulators, such as infliximab, vedolizumab, tocilizumab, mycophenolate, etc., can be added, if the irAE cannot be controlled with corticosteroids alone ( Table 1 ). Usually, treatment must be stopped if the patient develops severe toxicity, but it is not always linked to cessation of the anti-tumor benefit, and may even have the opposite effect, i.e., years of recurrence-free survival without any treatment ( 15 ). However, other patients experience an explosion of disease after the administration of high-dose corticosteroids or other immunosuppressants ( 16 ).…”