Laboratory features of tumour lysis syndrome following daratumumab monotherapy in relapsed/refractory multiple myeloma

Dear Editor, We read with great interest the recent report by Yavorkovsky et al (BJH 2020) where the authors document three separate cases of tumour lysis syndrome (TLS) in the setting of multiple myeloma (MM) therapy [1]. The authors postulate that an abrupt increase in serum-free light chain (SFLC) concentration in the setting of abrupt MM cell death may contribute significantly to the acute kidney injury seen in TLS [1]. TLS is rarely seen in multiple myeloma (MM) but has been reported following treatment with the proteasome inhibitors (PI) bortezomib and carfilzomib [2,3]. However, less is known about the risk of TLS with other anti-myeloma agents including immunomodulatory drugs (iMIDS) and monoclonal antibodies. Daratumumab is an anti-IgG1monoclonal antibody thathas significant anti-myelomaactivity, both as a single agent and in combination with other anti-myeloma agents in the setting of both de novo and relapsed disease [4,5]. To the best of our knowledge, TLShasnot been reported in the setting of daratumumab monotherapy in MM and therefore here we describe a case where laboratory evidence of TLS was observed after treatment with single-agent daratumumab. An 83-year-old lady with relapsed/refractory light-chain MM was admitted to hospital with progressive disease. Her medical history included congestive cardiac failure, asthma, melanoma and pulmonary embolism. She was diagnosed withMM2 years previously and at diagnosis had renal impairment requiring dialysis (serum creatinine was 402 μmol/L and calcium 2.42 mmol/L). Serum protein electrophoresis (SPEP) showed a small IgD kappa paraprotein and SFLC showed kappa > 1800 mg/L with lambda 5.4 mg/L (ratio > 337). Bone marrow trephine biopsy showed 70% kappa-restricted plasma cells and skeletal survey showed widespread lytic bone disease. She commenced


Dear Editor,
We read with great interest the recent report by Yavorkovsky et al (BJH 2020) where the authors document three separate cases of tumour lysis syndrome (TLS) in the setting of multiple myeloma (MM) therapy [1]. The authors postulate that an abrupt increase in serum-free light chain (SFLC) concentration in the setting of abrupt MM cell death may contribute significantly to the acute kidney injury seen in TLS [1]. TLS is rarely seen in multiple myeloma (MM) but has been reported following treatment with the proteasome inhibitors (PI) bortezomib and carfilzomib [2,3]. However, less is known about the risk of TLS with other anti-myeloma agents including immunomodulatory drugs (iMIDS) and monoclonal antibodies. Daratumumab is an anti-IgG1 monoclonal antibody that has significant anti-myeloma activity, both as a single agent and in combination with other anti-myeloma agents in the setting of both de novo and relapsed disease [4,5]. To the best of our knowledge, TLS has not been reported in the setting of daratumumab monotherapy in MM and therefore here we describe a case where laboratory evidence of TLS was observed after treatment with single-agent daratumumab.
An 83-year-old lady with relapsed/refractory light-chain MM was admitted to hospital with progressive disease. Her medical history included congestive cardiac failure, asthma, melanoma and pulmonary embolism. She was diagnosed with MM 2 years previously and at diag-   [7]. Although our patient did not develop clinical complications, she did meet the criteria for a diagnosis of laboratory TLS. There is sparse literature documenting the frequency of TLS in MM, however some studies suggest a higher frequency of TLS with PI-based therapy.
For example, a Japanese retrospective study of 64 patients found that out of a total of 124 chemotherapy regimens, TLS occurred in 13 out of the 124 courses (10.5%) [2] and also showed that the incidences of TLS were 17.5% and 3.2% for the bortezomib and non-bortezomib-based regimens, respectively, while no TLS occurred in patients treated with immunomodulatory drug (IMiD) containing regimens [2].
Reports of TLS associated with single-agent monoclonal antibody therapy are very rare in haematological cancer. For example, the SIRIUS study reported on the outcomes of 106 MM patients with relapsed/refractory MM treated with single-agent daratumumab and no cases of TLS or hyperphosphatemia were reported [4]. TLS was reported following treatment with elotuzumab, however the picture in this case was complicated by pre-treatment with lenalidomide and concomitant medications [8]. In a case of chronic lymphocytic leukaemia (CLL), a single test dose of obinutuzumab led to TLS and rapid tumour reduction [9].
In summary, we present the case of an 83-year-old lady who developed laboratory TLS following treatment with single-agent daratumumab. In keeping with the cases described by Yavorkovsky et al, our patient had a high burden of light chain secreting disease. We wish to highlight a very rare but potential complication of monoclonal antibody treatment in MM patients with large tumour burden and/or those with rapidly proliferating tumours. As daratumumab and other monoclonal antibodies become more widely used in both de novo and relapsed/refractory MM (and in other cancers); it is important that the potential for TLS is borne in mind and prophylactic measures are considered.

AUTHOR CONTRIBUTIONS
Louisa Shackleton, James Fay, and Elizabeth Smyth wrote the paper.
John Quinn, Siobhan Glavey, and Philip Murphy reviewed and edited the paper.