Tolerance and Efficiency of Anti-Programmed Death 1 Antibodies in Patients with Cancer and Preexisting Autoimmune or Inflammatory Diseases

Francois-Xavier Danlos¹, Anne-Laure Voisin², Valérie Dyevre³, Jean-Marie Michot¹, Emilie Routier⁴, Laurent Taillade⁵, Stéphane Champiat¹, Sandrine Aspeslagh¹, Julien Haroche⁶, Laurence Albiges⁷, Christophe Massard¹, Nicolas Girard⁸, Stéphane Dalle⁹, Benjamin Besse⁷, Salim Laghouati², Jean-Charles Soria¹, Christine Mateus⁴, Caroline Robert⁴, Emilie Lanoy³, Aurélien Marabelle^1,10 and Olivier Lambotte¹¹, ¹Drug Development Department, Gustave Roussy Institut, Villejuif, France, ²Unité Fonctionnelle de Pharmacovigilance, Gustave Roussy Institut, Villejuif, France, ³Service de biostatistique et d’épidémiologie, Gustave Roussy Institut, Villejuif, France, ⁴Department of dermatology, Gustave Roussy Institut, Villejuif, France, ⁵Department of medical oncology, Pitié Salpétrière Hospital, Paris, France, ⁶Internal Medicine 2. Referal center for SLE/APS, Hôpital Pitié-Salpêtrière, AP-HP, UPMC Univ Paris 06 & French National Reference Center For Systemic Lupus and Antiphospholipid Syndrome, Paris, France, ⁷Department of medical oncology, Gustave Roussy Institut, Villejuif, France, ⁸8. Department of Respiratory Medicine, National Expert Centre for Thymic Malignancies, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France, ⁹Department of dermatology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France, ¹⁰Immunotherapy program, Gustave Roussy Institut, Villejuif, France, ¹¹Internal Medicine, Hopital Kremlin Bicêtre, Kremlin Bicêtre, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: autoimmune diseases, cancer and cancer treatments, Immunotherapy

Session Information

Date: Monday, November 6, 2017

Title: T Cell Biology and Targets in Autoimmune Disease Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Patients with auto-immune or inflammatory diseases (AID) treated by immune check-points inhibitors (ICI) are intrinsically susceptible to develop immune related adverse events (irAE). We conducted this study to describe and analyze the tolerance and efficiency of anti-PD-1 antibodies in AID patients and to look for a clinical association between these preexisting immune conditions and patient’s outcome.

Methods:

We described patients with AID treated by ICI and conducted a prospective study in patients receiving anti-PD-1 antibody included in the registry REISAMIC (“Registry of Severe Adverse Events of Immunomodulating Monoclonal Antibodies in Oncology”) between 1st June 2014 and 31th December 2016. We analyzed the association between preexisting autoimmune disorder and irAE-free survival and overall survival.

Results:

We described 54 AID patients treated by ICI (mainly anti-PD-1 antibodies) including 45 AID patients which were analyzed and compared to non-AID patients among 397 patients from the registry REISAMIC. Cancer diagnoses included melanoma in 40 cases (74,1%), NSCLC in 10 cases (22,2%) and other cancers in 4 cases (2 renal cell carcinoma and urothelial carcinoma). Preexisting autoimmune or inflammatory diseases were vitiligo (n=17, 31,5%), cutaneous psoriasis (n=13, 32,5%), auto-immune thyroiditis (n=8, 20%), Sjögren syndrome (n=4, 10%), rheumatoid arthritis (n=4, 10%), auto-immune cytopenia (n=3, 17,5%), spondyloarthritis (n=2, 5%), multiple sclerosis (n=2, 5%) hidradenitis suppurativa (n=2, 5%), and in one case each: myasthenia gravis, polymyalgia rheumatica, polyarteritis nodosa, sarcoidosis, chronic cutaneous lupus, type 1 diabetes, primary nephrotic syndrome, acute tubulo-interstitial nephritis and aseptic abscesses syndrome. 10 patients had two concomitant different AID (18.5%). In 23 cases (42.6%), patient presented at least one grade 2 CTCAE irAE. Among them, 13 irAE (57%) were associated with a preexisting AID: increase of cutaneous psoriasis, development of psoriatic arthritis and pustular psoriasis, extension of vitiligo, hyperthyroidism, exacerbation of Sjögren’s syndrome, myasthenia crisis, polyarthritis or mesenteric abscesses leading to death. Eleven patients developed irAE which were not associated with the AID. 33 patients (61.1%) were alive at the last follow-up with a median time of 6.3 months (range 4.1-9.7 months). 19 patients (35.2%) pursued anti-PD-1 treatments at last follow-up with a median time of 4.9 months (range 3.4-7 months).

The irAE free survival was shorter in AID patients (median=5.4 months) as compared with non-AID patients (median=13 months, p=2,1.10^-4). Overall survival in AID patients did not differ to the one observed in non-AID patients (p= 0.38).

Conclusion:

In patients treated by anti-PD-1 antibodies, autoimmune and inflammatory diseases was associated with a higher risk of immune related adverse events and particularly flares which could be severe and fatal. AID and non-AID patient’s overall survival were not different. These points increase the importance of networks of collaborations between oncologists, organs specialists, and clinical immunologists to improve patients care.

Disclosure: F. X. Danlos, None; A. L. Voisin, None; V. Dyevre, None; J. M. Michot, BMS, 4; E. Routier, BMS, Roche, Novartis, Merk, Amgen, 4; L. Taillade, None; S. Champiat, AstraZeneca, BMS, Janssen, MSD, Roche, 4; S. Aspeslagh, None; J. Haroche, None; L. Albiges, None; C. Massard, Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Jansen, Lilly, Novartis, Pfizer, Roche, Sanofi Orion, 4; N. Girard, BMS MSD, AstraZeneca, OSE, Merck, Serono and Roche, 4; S. Dalle, Roche, Amgen, MSD, Merck, BMS, 4; B. Besse, None; S. Laghouati, None; J. C. Soria, None; C. Mateus, Merck, BMS, Pfizer, 4; C. Robert, Roche, BMS, MSD , merck, Amgen, Novartis, 5; E. Lanoy, None; A. Marabelle, None; O. Lambotte, MSD, Genzyme, 5.

To cite this abstract in AMA style:

Danlos FX, Voisin AL, Dyevre V, Michot JM, Routier E, Taillade L, Champiat S, Aspeslagh S, Haroche J, Albiges L, Massard C, Girard N, Dalle S, Besse B, Laghouati S, Soria JC, Mateus C, Robert C, Lanoy E, Marabelle A, Lambotte O. Tolerance and Efficiency of Anti-Programmed Death 1 Antibodies in Patients with Cancer and Preexisting Autoimmune or Inflammatory Diseases [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/tolerance-and-efficiency-of-anti-programmed-death-1-antibodies-in-patients-with-cancer-and-preexisting-autoimmune-or-inflammatory-diseases/. Accessed .

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