Immune-Related Adverse Events Associated with Immunotherapy in Solid Organ Tumors. Study of 102 Cases from a Referral Single Center for Last 3 Years

José Luis Martín-Varillas¹, Íñigo González-Mazón¹, Belén Atienza-Mateo¹, Marina Delagado Ruiz², Isabel Bernat Piña², Diana Prieto Peña³, Monica Calderón Goercke³, Lara Sánchez-Bilbao¹, Eva Peña Sainz-Pardo², Almudena García Castaño², Miguel Angel González-Gay² and Ricardo Blanco¹, ¹Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, ²Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, ³Rheumatology, Rheumatology. Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Adverse events, cancer and cancer treatments, Immunotherapy

Session Information

Date: Sunday, October 21, 2018

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster I: Checkpoint Inhibitors, Retroperitoneal Fibrosis

Session Type: ACR Poster Session A

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

Background/Purpose:

Immune checkpoint blockade therapy (ICTB) has shown remarkable benefit in different cancer types. Blockade of intrinsic down-regulators of immunity increases the activity of the immune system, which can lead to different immune-related adverse events. Our aim was to assess the immune-related adverse events in patients who received anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1). Our aim was to assess the incidence, treatment and evolution of immune-related adverse events due to ICTB.

Methods:

We set up an observational study of patients treated with Nivolumab and Pembrolizumab (anti-PD1), Atezolizumab (anti-PD-L1) and Ipilimumab (anti-CTLA-4) for solid organ tumors. All these patients were followed in a single reference University Hospital from March-2015 up to May-2018.

The main outcome was to determinate the incidence of immune-related adverse events of ICTB. The secondary objective was to assess the frequency and management of the rheumatological side effects.

Results:

We studied 102 patients (63♂/39♀) with a mean age of 60.6±9.7 with lung (n=63), gastric (n=3), bladder (n=1), kidney (n=11), melanoma (n=21) and colon cancer (n=3). Only 7 patients had a previous diagnosis of an immune-mediated disease: psoriasis (n=2), psoriatic arthritis (n=1), systemic lupus erythematosus (n=1), spondyloarthitis (n=1), rheumatoid arthritis (n=1) and skin lupus (n=1).

ICTB was performed as follows: pembrolizumab (n=35), nivolumab (n=52), atezolizumab (n=10) and ipilimumab (n=5).

After a median of 5 [2.5-10.5] months since the ICTB onset, we observed 87 (85.3%) patients with different autoimmune adverse effects (n=95), summarized in TABLE. ICTB discontinue was required in 39 patients. 36 patients received specific treatment (prednisone, antihistamine, levothyroxine and thiamazol), obtaining a good response in 31 cases (79.5%). ICTB was reintroduced in 28 patients (71.8%) after resolution of the adverse event, with an appropriate tolerance in all cases.

Rheumatological side effects were observed in 11 patients (10.8%): inflammatory arthralgia (n=6), arthritis (n=4), and aortitis (n=1). 7 of them required a temporary withdrawal of the immunotherapy, 3 were treated with NSAIDs and other 4 with oral prednisone (one of them also needed intraarticular corticosteroids). From the 7 patients with previous diagnosis of an immune-mediated disease, only 1 patient with psoriasis suffered a worsening of skin symptoms and other with psoriasis arthritis had a monoarthritis episode.

Conclusion:

In our study, the majority of autoimmune side effects due to ICBT were gastrointestinal, thyroiditis and cutaneous. The prevalence of rheumatological adverse effects was slightly higher than in pivotal studies. Most of them were with PD-1/PD-L1.

TABLE

Immune-Related Adverse Events	Anti CTLA-4 n=5	Anti PD-1 / PD-L1 n=97	TOTAL n=102
Gastrointestinal, n (%) (diarrhoea, colitis, mucositis)	1 (1.1)	38 (40)	39 (41,1)
Skin, n (%) (rash, erythema nodosum, psoriasis, vitiligo and alopecia)	1 (1.1)	12 (12.6)	13 (13.7)
Thyroid, n (%) (thyroiditis)	0 (0)	18 (18.9)	18 (18.9)
Articular, n (%) (arthralgia, arthritis)	0 (0)	10 (10.5)	10 (10.5)
Vasculitis, n (%) (aortitis)	0 (0)	1 (1.1)	1 (1.1)
LFTs alteration, n (%)	0 (0)	8 (8.4)	8 (8.4)
Nephritis, n (%)	0 (0)	6 (6.3)	6 (6.3)
TOTAL	2 (2.1)	93 (97.9)	95 (100)

+ LFT = liver function test.

Disclosure: J. L. Martín-Varillas, None; Í. González-Mazón, None; B. Atienza-Mateo, None; M. Delagado Ruiz, None; I. Bernat Piña, None; D. Prieto Peña, None; M. Calderón Goercke, None; L. Sánchez-Bilbao, None; E. Peña Sainz-Pardo, None; A. García Castaño, None; M. A. González-Gay, None; R. Blanco, None.

To cite this abstract in AMA style:

Martín-Varillas JL, González-Mazón Í, Atienza-Mateo B, Delagado Ruiz M, Bernat Piña I, Prieto Peña D, Calderón Goercke M, Sánchez-Bilbao L, Peña Sainz-Pardo E, García Castaño A, González-Gay MA, Blanco R. Immune-Related Adverse Events Associated with Immunotherapy in Solid Organ Tumors. Study of 102 Cases from a Referral Single Center for Last 3 Years [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/immune-related-adverse-events-associated-with-immunotherapy-in-solid-organ-tumors-study-of-102-cases-from-a-referral-single-center-for-last-3-years/. Accessed .

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