High Risk of Tumor Lysis Syndrome in Symptomatic Patients with Multiple Myeloma with Renal Dysfunction Treated with Bortezomib

Oiwa, Kana; Morita, Minoru; Kishi, Shinji; Okura, Miyuki; Tasaki, Toshiki; Matsuda, Yoshiki; Kojima, Tai; Hosono, Naoko; Ueda, Takanori; Yamauchi, Takahiro

doi:10.21873/anticanres.11274

Cited by 27 publications

(29 citation statements)

References 16 publications

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“…Additionally, the majority of patients also had either highly proliferative disease (as measured by plasmacyte labeling index) and/or unfavorable cytogenetics. Similar to this, a second retrospective study demonstrated that the presence of circulating plasma cells, higher International Staging System score for MM, higher baseline uric acid and creatinine were all risk factors for the development of TLS [ 4 ]. Consistent with this, the recent appearance of circulating plasmacytes on our patient’s blood differential suggests a more highly proliferative state, which may have been his major risk factor for TLS development.…”

Section: Discussionmentioning

confidence: 55%

“…Moreover, the patient had an elevation of creatinine > 1.5 times the upper limit of normal, thereby meeting the criteria for clinical TLS. Per retrospective single-center case series, the prevalence of TLS in MM was ~ 1 – 10% [ 2 , 4 ]. All patients in the first case series had bulky bone marrow disease, with none having less than 70% plasma cells on their bone marrow biopsy differential.…”

Section: Discussionmentioning

confidence: 99%

“…As described above, TLS is a relatively rare occurrence in MM. Many of these cases usually occur in a setting of high tumor proliferation [ 1 , 2 , 4 ] or in cases treated with bortezomib [ 5 ], melphalan [ 2 ], cyclophosphamide [ 2 ], or thalidomide [ 6 ]. Elotuzumab is a monoclonal antibody against signaling lymphocytic activation factor molecule F7 (SLAMF7), which causes the activation of natural killer cells against the MM cells and direct antibody-mediated cytotoxicity [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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A case of tumor lysis syndrome and acute renal failure associated with elotuzumab treatment in multiple myeloma

Atchison¹,

Humes²

2017

CNCS

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Renal dysfunction is a common comorbidity of multiple myeloma. However, tumor lysis syndrome is a rare cause of renal dysfunction in multiple myeloma. Elotuzumab is a newly US FDA-approved monoclonal antibody used in the treatment of refractory multiple myeloma. To our knowledge, elotuzumab has not been associated with a case of tumor lysis syndrome. We present the case of a patient who developed clinical tumor lysis syndrome 1 week after treatment with elotuzumab accompanied by renal failure with hyperphosphatemia, hyperkalemia, and profound hyperuricemia. His course was further complicated by significant epistaxis from the accumulation of dabigatran in acute renal failure. In spite of treatment with rasburicase and hemodiafiltration, the patient decompensated and eventually died. Risk factors for the development of tumor lysis syndrome in multiple myeloma are discussed.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A case of tumor lysis syndrome and acute renal failure associated with elotuzumab treatment in multiple myeloma

Atchison¹,

Humes²

2017

CNCS

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“…Because this dose did not affect the health of the mice with lower tumor burdens, we suspect the mice died from tumor lysis syndrome. This syndrome has been observed in myeloma patients treated with Bortezomib (16). Reducing the dose of the immunotoxin from 1.5 to 0.75 mg/kg prevented the mice from dying and caused durable complete responses in 60% of the mice (SI Appendix, Table S2).…”

Section: Discussionmentioning

confidence: 88%

Anti-BCMA immunotoxins produce durable complete remissions in two mouse myeloma models

Shancer

Liu

Nagata

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Multiple myeloma (MM) is a B cell malignancy for which new treatments are urgently needed. The B cell maturation antigen (BCMA) is a lineage-restricted differentiation protein highly expressed on myeloma. Recombinant immunotoxins (RITs) are proteins composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. We previously treated H929 myeloma s.c. tumors with anti-BCMA immunotoxins, very active on killing cultured cells, and observed tumor growth inhibition but not complete tumor responses. To determine if immunotoxins were more active against cells growing in the bone marrow (BM), the normal location of myeloma cells, we developed a BM mouse model that is more relevant to human disease. H929 cells were transfected with luciferase and GFP, enriched by flow, recycled through the BM of a mouse, and injected IV into nonobese diabetic scid γ mice (NSG) mice. A second myeloma mouse model used the MM.1S-GFP-luc cell line. Mice were treated IV with immunotoxins, and the tumor burden was assessed using bioluminescence imaging. We achieved complete durable remissions when treating mice with H929-GFP-luc cells with anti-BCMA RITs both leptomycin B-75 (LMB-75) [anti-BCMA-disulfide-stabilized (ds)-Fv-PE24] (where PE represents Pseudomonas exotoxin A) or LMB-70 (anti-BCMA-Fab-PE24) given every other day for 5-d (QOD×5) doses beginning on day 4 or day 8. Mice were disease free at 3 months; untreated mice became moribund around day 40. We also achieved long-term responses using the MM.1S-GFP-luc myeloma cell line. Treatment with an 1.5 mg/kg LMB-75 QOD×5 anti-BCMA RIT beginning on day 4 caused the complete disappearance of tumors for 80 days. To summarize, LMB-75 and LMB-70, our anti-BCMA RITs, induced complete durable responses in two myeloma models.

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“…To the best of our knowledge, this is the first reported case of TLS associated with ixazomib treatment in MM. There are many reports of bortezomib-induced tumor lysis, [ 9 , 10 ] but no case of ixazomib-related TLS has been reported. This patient had normal liver, kidney function, and electrolytes during treatment with bortezomib.…”

Section: Discussionmentioning

confidence: 99%

Ixazomib-associated tumor lysis syndrome in multiple myeloma

Jin

Yang²,

Chen³

et al. 2020

Medicine

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Rationale: Tumor lysis syndrome (TLS) is an oncologic emergency, but its incidence in MM is rare. To our knowledge, ixazomib has not been associated with TLS in MM. Patient concerns: The patient developed TLS after 10 days of treatment with ixazomib, accompanied by renal failure of hyperuricemia, hyperkalemia, and hyperphosphatemia. Diagnoses: MM (type IgG λ) was diagnosed according to the diagnostic criteria established by the International Myeloma Working Group and classified stage IIA by the International Staging System. TLS was diagnosed after the patient met all three criteria of the Cairo-Bishop TLS scoring system. Interventions: From April 8, 2017, the patient was treated with 3 courses of bortezomib, cyclophosphamide, and dexamethasone chemotherapy. From August 18, she received five courses of bortezomib combined with DCEP chemotherapy. On May 21, 2018 treatment was switched to lenalidomide, bortezomib, and dexamethasone for four courses. Ixazomib was started on October 10, 2018 with cyclophosphamide and dexamethasone. On October 19, 2018 vigorous intravenous hydration with sodium bicarbonate was initiated and peroral febuxostat was administered. Outcomes: On October 19, changes in hematological indicators raised concern for TLS worsening kidney function and decreasing urine output. She refused renal replacement treatment for TLS-induced acute kidney injury. On October 26th, the patient died of respiratory failure. Lessons: This case highlights the need to vigilant for the occurrence of TLS in patients undergoing MM treatment with ixazomib. Higher baseline uric acid or creatinine, rapidly progressive anemia, and raised lactate dehydrogenase (LDH) and β2-microglobulin may be surrogate markers of TLS.

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High Risk of Tumor Lysis Syndrome in Symptomatic Patients with Multiple Myeloma with Renal Dysfunction Treated with Bortezomib

Cited by 27 publications

References 16 publications

A case of tumor lysis syndrome and acute renal failure associated with elotuzumab treatment in multiple myeloma

A case of tumor lysis syndrome and acute renal failure associated with elotuzumab treatment in multiple myeloma

Anti-BCMA immunotoxins produce durable complete remissions in two mouse myeloma models

Ixazomib-associated tumor lysis syndrome in multiple myeloma

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