Acta Dermato-Venereologica, issue 9 97-9CompleteContent | Page 24

1138 SHORT COMMUNICATION Bortezomib Does Not Prevent the Occurrence of Kaposi’s Sarcoma in Patients with Haematological Malignancies: Two Case Reports Nathalie CHAVAROT 1,2 , Celeste LEBBÉ 3,4 , Eric THERVET 1,2 , Didier BOUSCARY 2,5 and Alexandre KARRAS 1,2 * Nephrology Department, Hôpital Européen Georges Pompidou, AP-HP, 20 rue Leblanc, FR-75015 Paris, 2 Université Paris Descartes, Dermatology Department, Saint Louis Hospital, AP-HP, Paris, 4 Université Paris René Diderot, and 5 Hematology Department, Cochin Hospital, AP-HP, Paris, France. *E-mail: [email protected] 1 3 Accepted Jun 8, 2017; Epub ahead of print Jun 9, 2017 Kaposi’s sarcoma (KS) is a rare angioproliferative tumour that affects skin and mucosa. Kaposi’s sarcoma herpes virus (KSHV or human herpes virus-8 (HHV-8)) is thought to be the causal agent (1). Besides endemic cases, KS in- duced by HHV-8 reactivation has been described among immunocompromised patients, such as those with AIDS and those with iatrogenic immunosuppression, mainly transplant recipients (2–4). Bortezomib is a proteasome inhibitor used for the treatment of multiple myeloma and plasma cell dyscra- sias, such as AL amyloidosis. No previous cases of KS occurring after bortezomib therapy have been reported. CASE REPORTS Case 1. A 69-year-old woman of Afro-Caribbean origin was referred in November 2012 for acute renal failure associated with lumbar pain and weight loss. She had no significant medical history. Clinical and biological investigations revealed IgG- lambda multiple myeloma with bone, renal and haematological complications (Table SI 1 ). Chemotherapy with bortezomib (1.3 mg/m 2 subcutaneously on days 1, 4, 8, 11, on a 21-day cycle), oral dexamethasone (20 mg twice a week) and cyclophosphamide (750 mg/m 2 intravenously (IV) on day 1), was initiated. After 3 cycles, the patient reached both renal (creatinine 152 µmol/l) and haematological partial remission. In February 2013, violaceous macules and papules were noticed on her left forearm and right arm, followed by similar bilateral lesions on both legs (Fig. 1A, B). Cutaneous biopsy demonstrated pathological features of typical KS. PCR of HHV-8 DNA was highly positive in tumour lesions, but negative in blood cells. HIV serology was negative. Oesophago-gastro-duodenoscopy, thoraco-abdominal computed tomography (CT) scan and F-18 FDG PET/CT ( 18 F-fluorodeoxyglucose-positron emission tomo- graphy–CT) showed no visceral involvement of KS. Treatment with bortezomib and cyclophosphamide was inter- rupted and lenalidomide was introduced as second-line treatment for myeloma, after renal function dose-adjustment (15 mg every other day), associated with dexamethasone (20 mg once a week). The cutaneous lesions regressed completely 2 months after initia- tion of lenalidomide. Blood HHV-8 PCR remained negative. The patient showed an excellent haematological response and renal function continued to improve. After a 3-year follow-up, the patient is still receiving lenalidomide maintenance therapy with sustained haematological remission. No KS relapse has been observed to date. Case 2. A 63-year-old woman of North African origin was refer- red in July 2013 for nephrotic syndrome associated with acute renal failure. Her medical history was significant for diabetes mellitus and hypertension, but also for cirrhosis due to hepatitis https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2727 1 doi: 10.2340/00015555-2727 Acta Derm Venereol 2017; 97: 1138–1139 Fig. 1. Baseline Kaposi’s sarcoma lesions in patient 1. C, treated with PEG-interferon-alpha and ribavirin, with sustained virological remission. She reported recent history of marked asthenia, associated with diarrhoea and vomiting. On admission, physical examination was unremarkable. Biological and pathological investigations revealed renal and digestive AL lambda amyloidosis (Table SI 1 ). Cardiac imaging and thoraco-abdominal CT were normal. Treatment with bortezomib (1.3 mg/m 2 subcutaneously on days 1, 8, 15 and 21, of a 28-day cycle), oral dexamethasone (20 mg twice a week) and oral cyclophosphamide (500 mg on days 1, 8, 15), was initiated in August 2013. Despite initial haematological response, nephrotic syndrome persisted with rapid deterioration of renal dysfunction, leading to initiation of haemodialysis in October 2013. During the third cycle of therapy, the patient developed exten- ded papular lesions of the thighs (Fig. S1 1 ). Skin biopsy showed characteristic features of KS with positive cutaneous HHV-8 latency-associated nuclear antigen (LANA) staining. HHV-8 vi- raemia was positive, with a viral load of 792 copies/ml (2.9 log). No visceral localization of KS was found on F-18 FDG PET/CT and thoraco-abdominal CT scan. Chemotherapy by bortezomib and cyclophosphamide was there­ fore stopped, and a combination of lenalidomide (5 mg 3 times a week, following dialysis) and dexamethasone was started in January 2014, in order to control plasma cell dyscrasia. Although the haematological response remained good after modification of chemotherapy, the patient died from septic shock in March 2014, due to enterococcal bacteraemia. No modification of the cutaneous lesions was observed before the fatal outcome. DISCUSSION We report here 2 cases of KS that developed following treatment with bortezomib and cyclophosphamide. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.