SHORT COMMUNICATION

Brentuximab Vedotin-induced Tumour Lysis Syndrome in Mycosis Fungoides: A Case Report

Berenika OLSZEWSKA^1,2*, Anna ZARYCZAŃSKA^1,2, Roman J. NOWICKI^1,2 and Małgorzata SOKOŁOWSKA-WOJDYŁO^1,2

¹Department of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdansk, Mariana Smoluchowskiego 17, PL-80-214, Gdańsk, and ²Department of Dermatology, Venereology and Allergology, University Clinical Centre, Gdańsk, Poland.
^*E-mail: berenika.olszewska@gumed.edu.pl

 

 

INTRODUCTION

Tumour lysis syndrome (TLS) is a life-threatening condition characterized by metabolic disturbances that occur spontaneously or following the initiation of cancer therapy. The metabolic abnormalities typical of TLS manifests as hyperkalaemia, hyperphosphatemia, hypocalcaemia, and hyperuricemia, potentially leading to severe renal impairment, cardiac arrhythmia, seizure, and possibly multi-organ failure and death (1, 2). TLS most frequently occurs in patients with haematologic malignancies and solid tumours undergoing treatment with chemotherapeutic agents or novel targeted therapies, including brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate (ADC). BV is approved for the treatment of classical Hodgkin’s lymphoma and other CD30-expressing lymphomas, including primary cutaneous T-cell lymphomas (pCTCLs). It has proved to be generally well tolerated, with the most commonly reported adverse events being peripheral sensory/motor neuropathy, followed by neutropenia. BV treatment may also result in life-threatening adverse events (AEs), including TLS. However, TLS occurrence in pCTCLs following treatment with a BV has not been reported yet. Here, we present the first case of TLS induced by BV in a patient with mycosis fungoides (MF).

CASE PRESENTATION

A 40-year-old man was diagnosed with MF stage IB (T3N0M0B0) in 2010. After 5 years of effective treatment with phototherapy (narrow band UVB, PUVA-bath, PUVA), localized radiotherapy, and acitretin, he experienced rapid aggravation of skin lesions, exhibiting erythroderma, and a high blood tumour burden of Sézary cells (absolute counts of atypical Sezary cells 3.3 × 10⁹/L), meeting haematologic criteria for B2 blood involvement. Despite multiple treatment methods, including bexarotene, interferon alpha-2a, and pegylated interferon, erythroderma persisted (Fig. 1), and the patient experienced progression in 2020, leading to lymphadenopathy (N3), visceral involvement (spleen and liver), and CD30+ expression confirmed in skin lesions.

Fig. 1. Persistent erythroderma.

The histopathological examination ruled out large-cell transformation of MF. Cytoreductive treatment with gemcitabine was initiated to reduce the lymphoma burden before BV implementation. Prior to BV initiation, his baseline laboratory values were: WBC 19.58 × 10⁹/L, neutrocytes 13.79 × 10⁹/L, haemoglobin 11 g/dL, serum creatinine 0.96 mg/dL, lactate dehydrogenase 2801 U/L, CRP 206 mg/L, ALT 102 U/l, AST 112 U/l, bilirubin 4.1 mg/dL, and normal range of electrolytes. The day after treatment initiation, he presented in poor general condition, with lymphadenopathy, yellowish skin discoloration, and increased inflammatory markers. Subsequent laboratory results showed WBC 12.49 × 10⁹/L, neutrocytes 8.7 × 10⁹/L, haemoglobin 9.4 g/dL, lactate dehydrogenase 8665 U/L, CRP 372 mg/L, bilirubin 7.11 mg/dL, and abnormal TLS-related serum values (Fig. 2). The abnormalities in uric acid, phosphorus, calcium, and creatinine, along with acute renal failure, were consistent with TLS according to Cairo and Bishop criteria (2). He was treated with intravenous fluids, rasburicase, calcium carbonate, allopurinol, broad-spectrum antibiotics (piperacillin/tazobactam, vancomycin, meropenem), tramadol, morphine, furosemide, haemodialysis due to anuria, and filgrastim followed by transfusions for pancytopenia. Despite extensive treatment, renal and hepatic parameters worsened, pancytopenia persisted, and the patient’s general condition deteriorated. The patient died of multiorgan failure on day 12 of hospitalization.

Fig. 2. Patient’s selected serum laboratory values after BV infusion, meeting the Cairo and Bishop criteria for TLS (2).

DISCUSSION

The incidence of TLS varies across different types of malignancies and therapeutic methods.

TLS is most common in high-grade NHL and acute leukaemia, whereas pCTCLs are classified as TLS low-risk diseases, with a defined risk below 1% (2).

While TLS is most frequently associated with cytotoxic therapy, it has also been observed following the use of steroids, methotrexate, monoclonal antibodies, tyrosine kinase inhibitors, and chimeric antigen receptor (CAR) T cells (3, 4). Moreover, novel, highly effective therapies may increase the risk of TLS in malignancies previously considered low risk, such as solid tumours (3).

The incidence of TLS following BV administration in pCTCLs remains unreported; thus, our case is the first to describe TLS occurring after BV treatment in a patient with MF. Pro et al. (5) reported TLS in 1 of 58 patients (1.7%) in a phase II trial of single-agent brentuximab for systemic anaplastic large-cell lymphoma. TLS in pCTCL is rare, with reported cases including spontaneous TLS in “SS preceded by MF” (6) and steroid-induced TLS in MF. (7). Despite lack of reported cases of TLS in pCTCL after BV treatment, it must be emphasized that patients with rapidly proliferating tumour and high tumour burden are at greater risk of developing TLS in pCTCLs (8). The presented case draws attention to modern and targeted anti-cancer therapies, which, due to their high efficacy, carry an increased risk of inducing TLS. Early risk stratification for TLS is crucial prior to the initiation of cancer treatment, with key predictors including renal dysfunction, hyponatremia, metastatic or large tumour burden, male sex, splenomegaly, and elevated creatinine, uric acid, and lactate dehydrogenase levels (9). Given the high mortality rate associated with TLS, ranging from 7% to 51%, (10, 11), it is essential to identify high-risk patients and implement appropriate prophylaxis to prevent TLS development.

ACKNOWLEDGEMENT

Conflict of interest disclosures: MSW has been a consultant and received compensation for lectures and the preparation of informational materials for doctors and patients from Takeda, Swixx, Celgene, and Recordati. BO, AZ, RJN have no conflicts of interest to declare.

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