Abstract 1069P
Background
Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSL) affecting the skin, lungs, thoracic lymph nodes, eyes and other organs. Accurate diagnosis and reporting of such rare events are essential to clinical practice and patient care.
Methods
We recently reported an estimated incidence of GSL among a subset of patients treated with adjuvant ipilimumab. In this analysis, we expanded our cohorts to include patients enrolled in the phase III adjuvant trials E1609 (N=1670) that tested ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose IFN-α (HDI) and S1404 (N=1207) that tested pembrolizumab versus patient/physician choice of ipi10 or HDI. We sought to estimate the incidence of GSL as reported by trial investigators in the combined datasets utilizing descriptive statistics as summarized in the table, along with the corresponding CTCAE grades.
Results
Among 2878 patients treated with ICIs or with HDI in E1609 and S1404, 523 were treated with ipi3, 932 with ipi10, 640 with pembrolizumab and 783 with HDI. A total of 11 GSL cases were reported. Cases were reported with ipi10, followed by pembrolizumab, ipi3 and HDI, respectively. Organs involved included skin and subcutaneous tissue (granuloma annulare, granulomatous dermatitis), eye (ocular sarcoidosis), lymph nodes (noncaseating granulomatous lymphadenitis), lung and mediastinal lymph nodes (sarcoidosis, granulomatous inflammation). Table: 1069P
| Organ(s) involved | Ipi3 (N=523) | Ipi10 (N=932) | Total Ipi (N=1455) | HDI (N=783) | Pembrolizumab (N=640) | |
| E1609 | Ocular | - | 1 (Gr 2) | 1 | - | NA |
| Skin | - | 1 (Gr 1) | 1 | - | NA | |
| Lung and lymphatic | 1 (Gr 3) | 2 (Gr 3 x2) | 3 | 1 (Gr 3) | NA | |
| S1404 | Skin | NA | 1 (Gr 1) | 1 | - | - |
| Lymphatic | NA | - | - | - | 1 (Gr 1) | |
| Lung and lymphatic | NA | 1 (Gr 2) | 1 | - | 2 (Gr 1, Gr 3) | |
| Total (%) | 1 (0.19%) | 6 (0.64%) | 7 (0.48%) | 1 (0.13%) | 3 (0.47%) |
Conclusions
Granulomatous and sarcoid-like lesions (GSL) following adjuvant anti-CTLA4 and anti-PD1 antibody therapy in high-risk melanoma were reported rarely. Reported cases ranged in grade from 1-3 and appeared manageable. Careful attention to these events and their reporting would be essential to better guide practice and management guidelines.
Clinical trial identification
E1609 trial was coordinated by the ECOG-ACRIN Cancer Research Group and supported by the United States National Cancer Institute (NCI) of the National Institutes of Health (NIH). S1404 trial was coordinated by the SWOG Cancer Research Group and supported by the Unites States National Cancer Institute (NCI) of the National Institutes of Health (NIH).
Editorial acknowledgement
Legal entity responsible for the study
The trials included was coordinated by the ECOG-ACRIN (E1609) and SWOG (S1404) and supported by the United States National Cancer Institute (NCI) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products or organizations does not imply endorsement by the US government.
Funding
NCI-NIH, Bristol Myers Squibb, Merck.
Disclosure
S.J. Lee: Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Full or part-time Employment, An Immediate Family Member: NantWorks; Financial Interests, Personal, Stocks/Shares, An Immediate Family Member: NantWorks. M. Othus: Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: GlycoMimetics; Financial Interests, Personal, Advisory Role: Cascadia Labs; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Daiichi Sankyo. J.M. Kirkwood: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Iovance Biotherapeutics; Financial Interests, Personal, Advisory Role: Elsevier; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Checkmate Pharmaceuticals; Financial Interests, Personal, Advisory Role: Harbour BioMed; Financial Interests, Personal, Advisory Role: ISTARI Oncology; Financial Interests, Personal, Advisory Role: OncoSec; Financial Interests, Personal, Advisory Role: Scopus BioPharma; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Castle Biosciences; Financial Interests, Institutional, Research Grant: Checkmate Pharmaceuticals; Financial Interests, Institutional, Research Grant: Immunocore; Financial Interests, Institutional, Research Grant: Iovance Biotherapeutics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb. V. Sondak: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: Replimune; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Polynoma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Replimune. A. Ribas: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Chugai Pharma; Financial Interests, Personal, Advisory Board: Sanofi-Genzyme; Financial Interests, Personal, Leadership Role: PACT Pharma; Financial Interests, Personal, Leadership Role: Arcus Biosciences; Financial Interests, Personal, Leadership Role: Lutris; Financial Interests, Personal, Stocks/Shares: Compugen; Financial Interests, Personal, Stocks/Shares: CytomX Therapeutics; Financial Interests, Personal, Stocks/Shares: Five Prime Therapeutics; Financial Interests, Personal, Stocks/Shares: Advaxis; Financial Interests, Personal, Stocks/Shares: Arcus Biosciences; Financial Interests, Personal, Stocks/Shares: Tango Therapeutics; Financial Interests, Personal, Stocks/Shares: PACT Pharma; Financial Interests, Personal, Stocks/Shares: Merus; Financial Interests, Personal, Stocks/Shares: Rgenix; Financial Interests, Personal, Stocks/Shares: ImaginAb; Financial Interests, Personal, Stocks/Shares: Lutris; Financial Interests, Personal, Stocks/Shares: Highlight Therapeutics; Financial Interests, Personal, Stocks/Shares: MapKure; Financial Interests, Personal, Stocks/Shares: 4c Biomed; Financial Interests, Personal, Stocks/Shares: Kite/Gilead; Financial Interests, Personal, Invited Speaker: RAPT Therapeutics; Financial Interests, Personal, Stocks/Shares: Isoplexis; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Chugai/Roche; Financial Interests, Personal, Other, Honoraria: Genentech/Roche; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: Vedanta Biosciences; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: Agilent; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb. K.F. Grossmann: Financial Interests, Personal, Advisory Role: Array BioPharma; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Natera. A.A. Tarhini: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Array BioPharma; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Immunocore; Financial Interests, Personal, Advisory Role: Pfizer/EMD Serono; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: BioNTech; Financial Interests, Personal, Advisory Role: Partner Therapeutics; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Prometheus; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: OncoSec; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Regeneron. All other authors have declared no conflicts of interest.