Safety of Immune Checkpoint Inhibitors for the Treatment of Melanoma, Bronchopulmonary and Urologic Neoplasms in Patients with Preexisting Autoimmune Disease

Alice Tison¹, Gilles Quere¹, Laurent Misery¹, Thierry Lesimple², Marie Marcq³, Stephanie Martinez⁴, Florence Brunet-Possenti⁵, Sandrine Mansard⁶, Nathalie Beneton⁷, Mickaël Lambert⁸, Christophe Roge⁸, Ouidad Zehou⁹, Francois Aubin¹⁰, Sarah Maanaoui¹¹, Camille Scalbert¹¹, damien giacchero¹², Nora Kramkimel¹³, François Skowron¹⁴, Anne Pham-Ledard¹⁵, Divi Cornec¹ and Marie Kostine¹⁵, ¹CHU Brest, Brest, France, ²Centre Eugène Marquis, Rennes, France, ³CH Vendee, La Roche-sur-Yon, France, ⁴CH Aix-en-Provence, Aix-en-Provence, France, ⁵CHU Bichat, Paris, France, ⁶CHU Clermont-Ferrand, Clermont-Ferrand, France, ⁷CH Le Mans, Le Mans, France, ⁸CH Morlaix, Morlaix, France, ⁹Hôpital Henri Mondor, Creteil, France, ¹⁰CHU Besancon, Besancon, France, ¹¹CHU Lille, Lille, France, ¹²Centre Antoine Lacassagne, Nice, France, ¹³CHU Cochin, Paris, France, ¹⁴CH Valence, Valence, France, ¹⁵CHU Bordeaux, Bordeaux, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: autoimmune diseases and cancer treatments

Session Information

Date: Tuesday, November 7, 2017

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster II

Session Type: ACR Poster Session C

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

Background/Purpose: Immune checkpoint inhibitors (ICIs), by inhibiting immunosuppressive molecules overexpressed in the tumoral environment such as CTLA-4 or PD1, increase the anti-tumor immune response and have been approved for an increasing number of cancers. However, they are responsible for immune related adverse effects (IRAEs), and patients with preexisting autoimmune diseases (PAD) have been excluded from clinical trials evaluating those molecules. The aim of this study was to evaluate their safety in routine practice in patients with PAD and the anti-tumoral response in this population.

Methods: Three national expert networks, focusing respectively on skin cancers, thoracic cancers, and inflammatory diseases, participated in the study. All patients who received an ICI despite a PAD were included in this nationwide retrospective study.

Results: 31 patients were included in the study (19 men (61%), median age of 66). Most frequent PADs were rheumatoid arthritis (n=9; 29%), psoriasis (n=6; 19%), lupus (n=4; 13%), ulcerative colitis (n=3; 10%), and spondyloarthritis (n=3; 10%). Eleven patients were receiving an immunosuppressive therapy when the ICI was initiated, and 10 had an active disease at that time. Neoplasm types were melanoma (n=16; 52%), non-small-cell lung carcinoma (n=12; 39%), and urologic neoplasms (n=3; 9%), with a median disease duration of 19 months. The majority of the patients (30/31) received an anti-PD1 drug, for a median duration of 4 months. PAD flares were frequent (n=18; 58%) but mostly mild: CTCAE grade 1-2 (n=12; 67%), grade 3-4 (n=3; 17%). 14 patients (78%) received corticosteroids or NSAIDs, and 3 (17%) methotrexate or acitretine for the treatment of these flares. IRAEs not associated with PAD appeared in 10 patients (32%): arthralgia (n=5), colitis (n=2), thyroiditis (n=2), vitiligo (n=2) with mild severity. None of the patients received TNF blockers, neither for a flare nor for an IRAE. 5 patients discontinued the immunotherapy because of an adverse effect. Regarding the cancer response rate, 4 patients over 11 who were taking an immunosuppressive treatment were responders (36%), versus 12 over the 20 other patients (60%).

Conclusion: PAD flares are frequent during ICI therapy and other IRAEs are also possible, usually easily managed with corticosteroids only. Anti-tumor response could be reduced when an immunosuppressor is ongoing at the beginning of the ICI, within the limit of the number of patients analyzed so far. Overall, the tolerance of ICIs in patients with PAD seems acceptable, but a multidisciplinary follow-up with the PAD referral physician is appropriate to manage frequent PAD flares and/or IRAEs.

Disclosure: A. Tison, None; G. Quere, None; L. Misery, None; T. Lesimple, None; M. Marcq, None; S. Martinez, None; F. Brunet-Possenti, None; S. Mansard, None; N. Beneton, None; M. Lambert, None; C. Roge, None; O. Zehou, None; F. Aubin, None; S. Maanaoui, None; C. Scalbert, None; D. giacchero, None; N. Kramkimel, None; F. Skowron, None; A. Pham-Ledard, None; D. Cornec, None; M. Kostine, None.

To cite this abstract in AMA style:

Tison A, Quere G, Misery L, Lesimple T, Marcq M, Martinez S, Brunet-Possenti F, Mansard S, Beneton N, Lambert M, Roge C, Zehou O, Aubin F, Maanaoui S, Scalbert C, giacchero D, Kramkimel N, Skowron F, Pham-Ledard A, Cornec D, Kostine M. Safety of Immune Checkpoint Inhibitors for the Treatment of Melanoma, Bronchopulmonary and Urologic Neoplasms in Patients with Preexisting Autoimmune Disease [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/safety-of-immune-checkpoint-inhibitors-for-the-treatment-of-melanoma-bronchopulmonary-and-urologic-neoplasms-in-patients-with-preexisting-autoimmune-disease/. Accessed .

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