Highlights
- •Potentially higher rate of sarcoidosis-like reactions (SLR) in patients who receive adjuvant immunotherapy than in patients with metastatic disease.
- •Differentiation between SLR and progression of disease in most cases only possible with biopsy.
- •No clinical symptoms of the SLR in our patients, no steroid treatment required.
- •No progression of the SLR after continuation of treatment.
- •Patients that developed SLR and patients that did not had an equal relapse rate (20%).
Abstract
Background
Anti-[programmed cell death protein 1 (PD-1)] antibodies nivolumab and pembrolizumab
were approved for adjuvant treatment of melanoma as they demonstrated improved relapse-free
survival. Currently, combined anti-PD-1 plus anti-[cytotoxic T-lymphocyte-associated
protein 4 (CTLA4)] blockade is being investigated in adjuvant and neoadjuvant trials.
Sarcoidosis-like reactions have been described for immune checkpoint inhibitors and
are most likely drug-induced. The reported rate of sarcoidosis/sarcoidosis-like reactions
within clinical melanoma trials is <2%. We observed that a remarkably higher number
of melanoma patients (10/45 patients, 22%) treated with immune checkpoint inhibitor
(ICI) within an adjuvant clinical trial-developed drug induced sarcoidosis-like reaction (DISR)
mimicking metastasis.
Case presentation
Of 45 stage III melanoma patients who were treated at our institute with adjuvant
ICI (either nivolumab alone or in combination with ipilimumab) within a two-armed,
blinded clinical trial, ten developed a DISR. Three of the ten patients were men,
median age was 52 years (range, 32–70 years). DISRs were asymptomatic and generally
detected radiographically at first radiographic imaging after the start of therapy
(median time, 2.8 months) and described as a differential diagnosis to tumour progression.
In one patient, DISR was only apparent 13.1 months after start of therapy and 4 weeks
after the end of ICI treatment. DISR presented as mediastinal/hilar lymphadenopathy
in 8/10 patients (as only site or in addition to lung, skin and/or bone involvement),
one patient had only lung and cutaneous, one patient only cutaneous DISR. Biopsies
from lymph nodes, skin and bone were taken in 8/10 patients, and histology confirmed
sarcoidosis-like reactions (SLRs). As patients were asymptomatic, no treatment for
DISR was required, and study treatment was stopped for DISR in only one patient due
to bone involvement. DISRs have resolved or are in remission in all patients. At a
median follow-up time of 15.3 months (range, 12–17.6 months), two patients experienced
melanoma relapse.
Conclusions
In most cases, sarcoidosis could only be differentiated from melanoma progression
on biopsy. Treating physicians as well as radiologists have to be aware of the potentially
higher rate of DISR in patients receiving adjuvant ICI. A thorough interdisciplinary
workup is required to discriminate from true melanoma progression and to decide on
continuation of adjuvant ICI treatment.
Keywords
Abbreviations:
ICI (immune checkpoint inhibitors), DISR (drug-induced sarcoidosis-like reaction), SLR (sarcoidosis-like reaction), EBUS (endobronchial ultrasound), ACE (angiotensin converting enzyme), sIL2R (soluble interleukin 2 receptor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: April 02, 2020
Accepted:
February 17,
2020
Received in revised form:
February 7,
2020
Received:
January 6,
2020
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
