To the Editor:
At present, minimal change disease (MCD) caused by PD-L1 inhibitors has not been reported. We have reported the first case of MCD caused by a PD-L1 inhibitor, durvalumab. A 75-year-old Asian man who developed nephrotic syndrome after 4 cycles of durvalumab administration for non−small cell lung cancer (NSCLC) was diagnosed with MCD by kidney biopsy. Complete remission (CR) was achieved soon after administration of prednisolone (PSL) (see Supplementary Material, Case Presentation and Supplementary Figures S1 and S2).
In the present case, MCD was thought to be caused by durvalumab rather than NSCLC, because proteinuria was observed soon after durvalumab administration, MCD was dramatically improved by administration of PSL, and disease activity of MCD and NSCLC are not consistent.1 Although most cases of renal immune-related adverse effects (irAEs) present with interstitial nephritis,2 rare cases of MCD by CTLA-4 inhibitors and PD-1 inhibitors have been reported (Table 1). The mechanism by which durvalumab causes MCD is assumed to be enhanced effects of T-cell−derived humoral factors2 and direct impairment of the glomerular filtration barrier via activation of CD80 in podocytes.3
Table 1.
Summary of published reports of minimal change disease associated with immune checkpoint inhibitors
| Authors, year | Age | Sex | Disease | ICPIs | Cr (baseline) (mg/dl) |
Cr (worst) (mg/dl) |
Proteinuria (pretreatment) (g/d) |
Proteinuria (posttreatment) (g/d) |
Treatment (/d) | Taper (days) | Outcome | Rechallenge | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No Rechallenge | Bickel et al., 2016 | 62 | M | Mesothelioma | Pembrolizumab | GFR 90 | GFR 27 | 19 | 0 | PSL 1 mg/kg | 70 | CR | |
| Kidd and Gizaw, 2016 | 55 | M | Melanoma | Ipilimumab | 1.2 | 5.2 | 9 | NA | PSL 2 mg/kg | NA | CR | ||
| Kitchlu et al., 2017 | 43 | M | Hodgkin lymphoma | Pembrolizumab | 0.76 | 3.93 | 10.3 | 3.1 | PSL 2 mg/kg | 180 | PR | ||
| Gao et al., 2018 | 40 | M | Hodgkin lymphoma | SHR-1210 (anti−PD-1) | 0.77 | NA | 30 | 0.18 | PSL 1 mg/kg | 56 | CR | ||
| Izzedine et al., 2019 | NA | NA | Melanoma | Pembrolizumab | GFR 90 | GFR 28 | 6 | NA | PSL (NA) mg | NA | ESRD | ||
| Izzedine et al., 2019 | NA | NA | Ileal NETs | Pembrolizumab | NA | 1.65 | 3.5 | NA | No treatment | NA | SD | ||
| E. Vaughan et al., 2020 | 57 | M | Tongue squamous cell carcinoma | Nivolumab | 0.79 | 2.29 | 2.1 | NA | PSL 75 mg | NA | SD | ||
| Rechallenge | Kitchlu et al., 2017 | 45 | M | Melanoma | Ipilimumab | 0.68 | 0.8 | 9.5 | 0.39 | PSL 1 mg/kg | 120 | CR | Recurrence without PSL |
| Saito et al., 2019 | 79 | M | Lung adenocarcinoma | Pembrolizumab | NA | NA | 13.8 | 0 | PSL 40 mg →10 mg | 56 | CR | No recurrence with PSL 10 mg/d | |
| Glutsh et al., 2019 | 68 | M | Melanoma | Pembrolizumab | normal | 2.86 | 19 | 0.33 | PSL 100 mg | 42 | CR | Recurrence without PSL |
CR, complete remission; ESRD, end-stage renal disease; GFR, glomerular filtration rate; ICPIs, immune checkpoint inhibitors; M, male; NA, not available, NETs, neuroendocrine tumors; PD-1, programmed death−1; PR, partial response; PSL, prednisolone; SD, stable disease.
As treatment, most patients were treated well with PSL 1 to 2 mg/kg per day and tapered off over 6 to 26 weeks. If renal irAEs are grade 2 or lower and if renal function is maintained at normal after treatment, ICPIs may be resumed.4 In the present case, rechallenge with durvalumab will be considered in the future, because the tumor was not resected surgically. Regarding acceptance of rechallenge ICPIs, 31 cases of renal irAE were resumed ICPIs, 7 cases relapsed, and 6 cases had renal recovery.5 In addition, 3 patients with MCD by irAE were resumed ICPIs; 2 of these patients relapsed who did not receive maintenance therapy, whereas the patient who did not relapse received maintenance therapy with PSL 10 mg/d (Table 1). From these facts, we consider that the present case will require maintenance therapy with PSL when resuming durvalumab for worsening NSCLC.
Disclosure
All the authors declare no completing interests.
Author Contributions
MT and KF drafted the manuscript. MT, KF, and AK examined the patient. All authors revised the paper, and all authors approved the final version of the manuscript.
Footnotes
Background
Case Presentation
Discussion
Disclosure
Patient Consent
Supplementary References
Figure S1. Representative images of kidney biopsy.
Figure S2. Clinical course of the present case.
Supplementary Material
Background
Case Presentation
Discussion
Disclosure
Patient Consent
Supplementary References
Figure S1. ▪▪▪
Figure S2. ▪▪▪
References
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