Table 1

Characteristics of the patients having developed DI-LE following treatment with anti-PD(L)1 immunotherapy

Gender, age, cancer histologyPrevious cancer treatmentsDrugCausal relationshipTime to occurrence of DI-LE*
(in weeks)
DI-LE form†Severity gradeHistopathological characteristics of a skin biopsyDirect immunofluorescence in skin biopsyAutoimmune biology in serum‡Serum creatine kinase (normal value <145 IU/L)Other irAEsTreatment for cutaneous lupus, and outcomeBest overall antitumour response, and reintroduction of PD(L)1 (or reason for withdrawal)
Patient 1, woman, 48 years old, triple-negative breast carcinomaFarmorubicine-endoxan-5-fluorouracil; eribulin, capecitabine; gemcitabineAtezolizumabLikely6SCLE
Clinical aspect and location: erythematosus, neckline
1Inflammatory monomorphic lymphocyte infiltrate in perivascular and periadnexal sites throughout the dermis. Alcian blue staining revealed mucin deposits in the dermis.Positive for IgG, linear, moderate, epidermal dermal junction
Negative for C3d
Titre for ANA negative (<1/80), aDNA<10, ENA negative complement in normal range (C3=1.73; C4=0.26)
Normal (75 IU/L)NoTopical steroids, resolution in 2 weeksPR
No interruption of atezolizumab
Patient 2, woman, 80 years old, diffuse large B-cell lymphomaR-CHOP; R-GEMOX; R-lenalidomideNivolumabLikely14SCLE
Clinical aspect and location: papulosquamous erythematous in the lower limbs, symmetrical
2Inflammatory perivascular lymphocytic infiltrate of the upper and middle dermis. Alcian blue staining revealed mucin deposits.NegativeNegative
Titre for ANA<1/80; aDNA<10; ENA negative
Low complement C4 and CH50 but normal C3 (C3=1.53; C4<0.02; CH50<10)
Normal (28 IU/L)Yes: hepatitis grade 2Topical steroids, resolution in 3 weeksPD
Temporary withdrawal of immunotherapy due to lupus, and then definitive withdrawal of nivolumab due to disease progression
Patient 3, woman, 66 years old, carcinoma epidermoidRadiotherapy; carboplatin-cetuximab-5-fluorouracil; paclitaxel-cetuximab; methotrexate-carboplatineNivolumabLikely4SCLE
Clinical aspect and location: erythematosus on the trunk, back and face
2Perivascular lymphocytic infiltrate of the upper dermis with discrete vacuolisation of the epidermal basal layer. Alcian blue staining revealed mucin deposits in the dermis.NegativePositive with ANA+ and SSA+
Titre for ANA=1/640; aDNA<10; ENA=1.5 weakly positive; SSA=94 U/mL, complement in normal range (C3=1.42; C4=0.2; CH50 not done)
Normal (30 IU/L)NoTopical steroids, resolution in 2 weeksSD
Temporary withdrawal of immunotherapy due to lupus
Patient 4, man, 63 years old, melanomaNonePembrolizumabCertain22SCLE
Clinical aspect and location: generalised, clearly erythematosus, papular and macular aspects on the trunk, back, abdomen and thorax
Systemic lupus erythematosus (SLICC criteria4 were SCLE+arthralgia+positive serum antibodies)
3Lichenoid dermatosis with staged apoptotic bodies in the epidermis. Peripheral inflammatory mononuclear infiltrate in the upper dermis. Alcian blue staining did not reveal any mucin deposits in the dermis.Positive for IgG: discontinuous low-intensity band and epidermal dermal junction. C3d positive: rough bandPositive with SSA+/SSB+
Titre for ANA>1/1280 (mottled aspect); aDNA<10; ENA>28 highly positive with SSA>241 U/mL and SSB=86 U/mL (n<7), complement in normal range (C3=1.07; C4=0.21; CH50>60)
238 IU/L when lupus appeared, then 181 IU/L
15 days later, then return to normal levels
Yes: vitiligo universalis, hepatitis grade 2Topical steroids, oral hydroxychloroquine, resolution in 4 weeksCR
Permanently discontinued due to the adverse event and the CR
Patient 5, man, 48 years old, melanomaDacarbazine-fotemustine; ipilimumabPembrolizumabCertain10Chilblain lupus on the toes1 Not performed Not performed Negative
Titre for ANA<1/80; aDNA<10; ENA not done; complement in normal range (C3=1.17; C4=0.2; CH50=49.3)
Normal (58 IU/L)Yes: vitiligo universalisTopical steroids, resolution in 2 weeksPR
No discontinuation of pembrolizumab
Median (range) age 63 (48–80) years
Median (range): 10 (4–22) weeksPositive in two of four cases tested (50%)ANA positive in two of five cases (40%)
  • *Time between the first infusion of anti-PD(L)1 and the onset of symptoms of lupus erythematosus.

  • †Among Obermoser et al.7

  • ‡Serum assays for autoimmune factors, with normal values indicated: ANA, serum titre, normal <1/80; aDNA, normal <10 IU/mL; ENA, ratio, normal <1.1 (ratio=sample absorption/standard absorption); SSA, normal <7 U/mL; SSB, normal <7 U/mL; C3, normal values=0.9–1.80 g/L; C4, normal values=0.10–0.40 g/L; CH50, normal value >31.6; creatine kinase (CK), normal values=0–145 IU/L.

  • aDNA, anti-DNA; ANA, antinuclear antibody; CH50, 50% complement haemolytic; CR, complete response; DI-LE, drug-induced lupus erythematosus; ENA, extractable nuclear antigen; irAE, immune-related adverse event; PD, progressive disease; PR, partial response; R-CHOP, rituximab-cyclophosphamide hydroxyadriamycine oncovin prednisone; R-GEMOX, rituximab-gemcitabine oxaliplatine; SCLE, subacute cutaneous lupus erythematosus; SD, stable disease; SLICC, Systemic Lupus International Collaborating Clinics4; SSA, Sjögren’s syndrome-related antigen A; SSB, Sjögren’s syndrome-related antigen B.