Long-term follow-up of patterns of melanoma early and late recurrence after adjuvant anti-PD1 therapy.

Abstract

e21527 Background: Despite the promise of immune checkpoint inhibitors (ICI), 25-30% of stage III/IV patients (pts) with (w) resected melanoma develop relapsed disease by 12 months (mon) after adjuvant (adj) anti-PD1 (aPD1). Understanding the recurrence patterns and resistant mechanisms is critical to develop strategies for better outcomes. Methods: Through an approved protocol by Institutional IRB, 172 ICI naive pts w resected high-risk melanoma who received adj aPD1 were consented and followed prospectively. Clinical outcomes were assessed by ORR per RECIST 1.1, PFS, OS and time to next treatment (TTNT). Results: With median follow up of 36 mon (5-98), melanoma recurred in 90 (52%) of 172 pts treated w adj aPD1, including 59 (66%) w early PD (PD while on or w/in 3 mon of last adj aPD1) and 31 (34%) w late PD (PD > 3 mon from last adj anti-PD1). 57 (67%) males, median age 56 (25-84) at C1D1, 3/82/5 at stage II/III/IV. Subtypes included 43 (48%) superficial spreading and 24 (27%) nodular. 44 (49%) had locoregional PD while 46 (51%) had distant PD. 6 pts died at relapse or shortly after. Of the 24 pts w resectable recurrence, the subsequent PD rate after surgery (sx) was 5/14 (36%) if followed by adj aPD1 +/- others, 4/7 (57%) by adj ipi/nivo, and 3/3 (100%) by adj targeted therapy which is associated w much shorter median TTNT. Of the 60 pts who received systemic therapy only after recurrence, ORR to rechallenge w aPD1, anti-CTLA4 + aPD1, targeted therapy +/- aPD1, TVEC/other injectables +/- aPD1, Opdualag and chemo were 57%, 26%, 62%, 30%, 0% and 0%; including those w early PD, ORR of 0% (0/2), 25% (5/20), 63% (5/8), 22% (2/9), 0% (0/1) and NA; and w late PD, ORR of 80% (4/5), 29% (2/7), 60% (3/5), 100% (1/1), 0% (0/1) and 100% (1/1). Median TMB tends to be higher in pts who benefited from systemic ICI, except pts who benefited from TVEC had much lower median TMB (1 vs 17). Conclusions: With the known longest follow up, half of pts w high risk resected melanoma developed PD after adj aPD1, and 2/3rds of those are early PD. Half of resectable relapse can be managed by sx followed by adj ICI w/o further PD. Most of the late PD rechallenged w aPD1 can still respond. Pts w lower TMB might benefit more from TVEC approach. Sx + adj aPD1 +/- others (no ipi) N=14 Sx + adj ipi/nivo N=7 Sx + adj targeted therapy N=3 Rechallenge w aPD1 N=7 Anti-CTLA4 + aPD1 N=27 Targeted therapy +/- aPD1 N=13 TVEC +/- `aPD1 N=10 Opdualag N=2 Chemo N=1 CR/PR or NED 9 3 0 4 7 8 3 0 1 SD 0 0 0 0 1 1 0 0 0 PD 5 4 3 3 19 4 7 2 0 ORR or non-relapse rate 64% 43% 0% 57% 26% 62% 30% 0% 0% Median PFS (m) 7 (2-70) 8 (2-44) 6 (1-16) 5 (1-32) 3 (1-59) 4 (1-17) 3 (0.7-12) 4 (4-5) 1 Median OS (m) 22 (3-69) 15 (8-50) 21 (8-39) 20 (2-44) 10 (1-61) 16 (3-67) 28 (6-94) 12 (6-18) 3 Median TTNT (m) 11 (3-70) 11 (3-44) 6 (1-18) 10 (3-32) 9 (1-59) 7 (1-26) 5 (0.7-13) 6 (5-6) 10 Median TMB CR/PR/NED vs PD (mut/mb) 12 / 7 (3-25) 5 /3 (3-7) NA / 2 80 / NA 13 / 5 (0.2-13) NA / 8 (0.4-20) 1 / 17 (0.6-17) NA / NA 1.3 BRAF V600 CR/PR/NED vs PD 20%/40% 67%/75% 0%/100% 25%/0% 43%/35% 100%/100% 67%/71% 0%/0% 0%