Abstract 3632
Background
Combination IPI+PD1 immunotherapy has a high initial response rate, but patients can subsequently progress. The best management of this acquired resistance is unknown. We sought to explore the efficacy and safety of rechallenge IPI+PD1 in this setting.
Methods
Retrospective data from four melanoma centres were reviewed. Demographics, disease characteristics, initial and rechallenge treatment efficacy and toxicity were examined.
Results
15 patients (pt) were identified: 60% male, median age 51y, 40% BRAF mutant. 14 pt received IPI+PD1 as 1st line of treatment, 1 received prior BRAFi+MEKi. 9 pt received ipilimumab (I) 3mg/Kg and nivolumab (N) 1mg/kg (I3N1), 5 received I 1mg/kg and pembrolizumab (P) 2mg/kg, 1 patient I 100mg q12w/P200mg q3w, with a median 4 cycles of I. 1 pt had CR, 10 had PR, and 4 prolonged SD (>6 months) to initial treatment. 7 pt (47%) developed significant irAE (4 hepatitis, 2 colitis, 1 pneumonitis), of which 6 (85%) ceased IPI + PD1 and only 1 pt continued PD1 alone. Median time to progression (TTP1) was 11 months (range 5-31 months). After progression, 5 (33%) had no intervening systemic therapy prior to rechallenge IPI+PD1 (of which 3 progressed on while receiving maintenance PD1), 5 had BRAFi/MEKi (33%), 2 (13%) had anti-PD1 monotherapy, 2 (13%) had investigational immunotherapy agents on a trial, and 1 pt had DTIC. At rechallenge, 13 pt received I3N1, 1pt I1N3 and 1 pt I3q12w + N1q2w, with a median 2 cycles of I. Only 1 pt had PR, 1 had SD, while 13 (87%) had PD, with mPFS2 only 2.7 mo (95% CI 2- NA). OS from rechallenge was 7.5 mo (95% CI 6.7- NA). All 7 pt with prior treatment-limiting irAE had the same irAE recur, except for 1 pt who died one week after re-exposure of PD, and 1 pt with prior pneumonitis who remained on 10mg prednisone without recurrence.
Conclusions
Rechallenge with IPI + PD1 appears to have little efficacy in those with acquired resistance and prior toxicity often recurs. An expanded multi-institutional analysis is under way.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Hepner: Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Roche. M.S. Carlino: Advisory / Consultancy: BMS; Advisory / Consultancy: Merck; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: AMGEN; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche. D.B. Johnson: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy: BMS; Advisory / Consultancy: Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Incyte; Travel / Accommodation / Expenses: Genentech. O.A. Michielin: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MSD. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck; Advisory / Consultancy: MSD; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.
Resources from the same session
3556 - Long-term efficacy of combination nivolumab and ipilimumab for first-line treatment of advanced melanoma: a network meta-analysis
Presenter: Peter Mohr
Session: Poster Display session 3
Resources:
Abstract
4543 - Long-term real-world (RW) outcomes in patients with advanced melanoma (MEL) treated with ipilimumab (IPI) and non-IPI therapies: IMAGE study
Presenter: Stéphane Dalle
Session: Poster Display session 3
Resources:
Abstract
4523 - Prognostic Factors for efficacy of Ipilimumab used after AntiPD1 and/or BRAF+MEK inhibitors in Melanoma Patients: an Italian Melanoma Intergroup study
Presenter: Riccardo Marconcini
Session: Poster Display session 3
Resources:
Abstract
3732 - Clinicopathologic characteristics of immune colitis in melanoma patients treated with combination ipilimumab and anti-PD1 (IPI+PD1) and PD1 monotherapy.
Presenter: Kazi Nahar
Session: Poster Display session 3
Resources:
Abstract
5005 - Real-world outcomes of ipilimumab plus nivolumab for advanced melanoma in the Netherlands
Presenter: Michiel van Zeijl
Session: Poster Display session 3
Resources:
Abstract
5524 - Utilization of Real-World Data to Assess the Effectiveness of Immune Checkpoint Inhibitors (ICIs) in Elderly Patients with Metastatic Melanoma
Presenter: D Scott Ernst
Session: Poster Display session 3
Resources:
Abstract
5884 - Tumor mutational burden and response to PD-1 inhibitors: an analysis of 89 cases of metastatic melanoma.
Presenter: Léa Dousset
Session: Poster Display session 3
Resources:
Abstract
3120 - Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma.
Presenter: Elisa Rozeman
Session: Poster Display session 3
Resources:
Abstract
2157 - Immune status defined by molecular information layers predicts response to pembrolizumab treatment in advanced melanoma
Presenter: Guillermo Prado-Vázquez
Session: Poster Display session 3
Resources:
Abstract
2553 - Interim analysis of a phase Ib study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild type melanoma progressing on prior anti-PD-L1 therapy
Presenter: Shahneen Sandhu
Session: Poster Display session 3
Resources:
Abstract