A multicenter analysis of melanoma recurrence following adjuvant anti-PD1 therapy.

Abstract

9502 Background: Adjuvant anti-PD1 monoclonal antibodies (mAbs) prolong recurrence-free survival in high-risk resected melanoma, however patients (pts) recur during or after therapy. The patterns of recurrence and optimal management are unclear. Methods: Pts from 15 melanoma centres who recurred having received adjuvant anti-PD1 mAbs (adj-PD1) for resected stage III/IV cutaneous melanoma were included. Disease characteristics, adjuvant treatment, recurrence characteristics, subsequent management and outcomes were examined. Results: 137 pts had melanoma recurrence; 97 (71%) during adj-PD1 and 40 (29%) following treatment cessation (25 had stopped early for toxicity after a median 3 months, 14 after completing 12 months, 1 who withdrew consent after 1 month). Median time to recurrence from start of anti-PD1 was 4.6 months (IQR 2.7-8.5), and median follow up from recurrence was 7.7 months (IQR 3.8-12.3). At 1st recurrence, 78 (57%) pts had distant disease (including 22 with both locoregional and distant), 59 (43%) had locoregional disease only. Of those who recurred locally, 22/59 (37%) later developed distant disease. 26 (19%) pts have died. 81 (59%) pts had systemic therapy for distant recurrence (either 1st recurrence or subsequent). Of those who recurred during adj-PD1, no pts (0/20) subsequently responded to anti-PD1 alone (N = 8) or with any investigational agent (N = 12; anti-LAG3, IDOi, MEKi, TLR9 agonist); 9/27 evaluable pts (33%) responded to ipilimumab-based therapy (alone or in combination with anti-PD1), and 15/19 (79%) responded to BRAF/MEKi . Of those who recurred after ceasing adj-PD1, 2/5 (40%) responded to anti-PD1 monotherapy, 2/5 (40%) responded to ipilimumab-based therapy, 7/8 (88%) responded to BRAF/MEKi. Conclusions: These data suggest minimal activity of further anti-PD1 monotherapy in those who recur while on adj-PD1, but possible activity in those who recur off treatment. Anti-CTLA4 and BRAF/MEKi therapy appear active in those who recur on or following adj-PD1. Data on locoregional recurrence and its management will also be presented.

Rechallenge with checkpoint inhibitors in metastatic melanoma

“…Here, the analysis included 85 patients from various studies . In this context, there has also been an interesting recent study describing anti‐PD1 rechallenge after disease progression in patients who had previously received anti‐PD1 antibodies in an adjuvant setting . Some patients, whose relapse occurred only after adjuvant anti‐PD1 treatment had been discontinued and who were then rechallenged with the same treatment, did show a response (2/5 cases).…”

Treatment of High Risk Resected Melanoma in Australia: Current Landscape and Practises

“…Preliminary retrospective data presented at ASCO for patients relapsing after adjuvant immunotherapy found that the majority of disease recurrence occurred within 5 months of commencing adjuvant immunotherapy. No patients who recurred on adjuvant‐PD1 inhibitors and subsequently treated with further single agent anti‐PD1 agents responded, whilst almost 80% responded to subsequent targeted therapy 25 and 33% responded to ipilimumab based therapy. Thus, patients who relapse on single agent anti‐PD1 inhibitors are likely to benefit most from treatment with combination immunotherapy, targeted therapy or enrolment into a clinical trial, as further treatment with another anti‐PD1 agent in isolation is unlikely to be effective.…”

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge” (December 4th–5th, 2019, Naples, Italy)

“…This raises the question of whether the prospect of ‘cure’ for some patients is being compromised by single-agent PD-1 inhibition in the adjuvant setting. There is early evidence of a reasonable response rate to retreatment with PD-1 inhibition following post-adjuvant immunotherapy treatment relapse, with clinical activity in patients with recurrent melanoma treated with anti-PD-1 after adjuvant PD-1 therapy [ 38 ]. However, the durability of response is unknown.…”