Bortezomib-induced severe pulmonary complications in multiple myeloma: A case report and literature review

Li, Jingbo; Chen, Shuda; Hu, Yinghong; Cai, Jing

doi:10.3892/ol.2016.4204

Cited by 13 publications

(12 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pulmonary toxicity, albeit rare, has also been reported with PIs targeting the 20S proteasome subunit [14][15][16]. In a recent literature review of 35 reports of pulmonary toxicity attributed to bortezomib, most events were noted to occur after the first Fifteen patients were enrolled and 14 patients were treated.…”

Section: Discussionmentioning

confidence: 99%

Phase 1 study of the protein deubiquitinase inhibitor VLX1570 in patients with relapsed and/or refractory multiple myeloma

Rowinsky¹,

Paner

Berdeja

et al. 2020

Invest New Drugs

View full text Add to dashboard Cite

This phase 1 study sought to characterize the safety, tolerability, and pharmacokinetic behavior of VLX1570, a small molecule inhibitor of the deubiquitinases (DUBs) that remove sterically bulky ubiquitin chains from proteins during processing in the19S regulatory subunit of the proteasome, in patients with relapsed and refractory multiple myeloma (MM). Fourteen patients were treated with escalating doses of VLX1570 ranging from 0.05 to 1.2 mg/kg as a brief intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Due to its poor aqueous solubility, VLX1570 was formulated in polyethylene glycol, polyoxyethylated castor oil, and polysorbate 80 and administered as a brief intravenous (IV) infusion via a central venous catheter. Anti-myeloma effects were noted at doses at or above 0.6 mg/kg, however, two patients treated at the 1.2 mg/kg dose level experienced severe, abrupt, and progressive respiratory insufficiency, which was associated with diffuse pulmonary infiltrates on imaging studies, similar to those rarely noted with bortezomib and other inhibitors of the 20S proteasome, culminating in death. Although the contribution of VLX1570's formulation to the pulmonary toxicity could not be ruled out, the severity and precipitous nature of the toxicity and the steep relationship between dose and toxicity, the study was discontinued. Despite the severe pulmonary toxicity noted with VLX1570, efforts directed at identifying DUB inhibitors with greater therapeutic indices appear warranted based on the unique mechanism of action, robustness of preclinical antitumor activity, and activity of the DUB inhibitors in MM resistant to PIs targeting the 20S proteasome subunit.

show abstract

Section: Discussionmentioning

confidence: 99%

Phase 1 study of the protein deubiquitinase inhibitor VLX1570 in patients with relapsed and/or refractory multiple myeloma

Rowinsky¹,

Paner

Berdeja

et al. 2020

Invest New Drugs

View full text Add to dashboard Cite

show abstract

“…Multiple myeloma (MM) is a malignant plasma cell neoplasm characterized by plasma cells accumulating in the bone marrow and subsequent destruction of bone, symptoms of bone marrow failure and organ dysfunction ( 1 ). MM is responsible for ~1% of all cancers and 10% of hematological cancers ( 2 , 3 ). The median age at diagnosis of MM is 70 years ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…MM is responsible for ~1% of all cancers and 10% of hematological cancers ( 2 , 3 ). The median age at diagnosis of MM is 70 years ( 3 ). The median survival of patients with MM was <1 year prior to the introduction of alkylating agents ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…The median age at diagnosis of MM is 70 years ( 3 ). The median survival of patients with MM was <1 year prior to the introduction of alkylating agents ( 3 ). The introduction of novel agents, including bortezomib, thalidomide and lenalidomide, for the treatment of MM patients has significantly improved clinical outcomes ( 1 – 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…The median survival of patients with MM was <1 year prior to the introduction of alkylating agents ( 3 ). The introduction of novel agents, including bortezomib, thalidomide and lenalidomide, for the treatment of MM patients has significantly improved clinical outcomes ( 1 – 3 ). However, a concerning finding has been the increase in the incidence of secondary malignancies ( 4 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Secondary lymphoblastic leukemia occurring 38 months after the primary diagnosis of multiple myeloma: A case report

Zhan²,

Zhang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Multiple myeloma (MM) is a malignant plasma cell neoplasm characterized by the accumulation of plasma cells in the bone marrow, the subsequent destruction of bone and organ dysfunction. The present study describes the case of a 66-year-old male patient who presented with the typical clinical manifestations of MM. The patient was administered a bortezomib and dexamethasone regimen for 2 cycles and achieved complete remission. Lenalidomide, vincristine, pirarubicin, dexamethasone, melphalan and thalidomide was used successively in consolidation therapy and maintenance therapy. The patient developed secondary B-cell lymphoblastic leukemia 38 months after the primary MM diagnosis was made. Owing to the exposure of the patient to a variety of therapeutic agents, it could be inferred that multiple immune defects may have played an important role in the secondary lymphoblastic leukemia of the patient. Microscopic examination and flow cytometry detection were important in identifying the secondary malignancy in this MM case.

show abstract

Treatment of children with relapsed and refractory acute lymphoblastic leukemia with mitoxantrone, vincristine, pegaspargase, dexamethasone, and bortezomib

August

Guest

Lewing

et al. 2019

Pediatric Blood & Cancer

View full text Add to dashboard Cite

BackgroundThe treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in children is challenging and new treatment options are needed. Bortezomib is a proteasome inhibitor with activity in pediatric acute lymphoblastic leukemia. Adding bortezomib to standard reinduction chemotherapy in relapsed and refractory pediatric ALL has produced very good response rates in prior studies.MethodsWe evaluated bortezomib in combination with reinduction therapy (ALL R3) in 10 children with relapsed or refractory ALL. Bortezomib (1.3 mg/m2/dose) was administered to patients on days 1, 4, 8, and 11. In addition, patients received mitoxantrone, dexamethasone, pegaspargase, vincristine, and intrathecal methotrexate over 4 weeks.ResultsOf the 10 patients, eight (80%) achieved a complete remission (CR) or complete remission with incomplete recovery (CRi). Of the patients in CR, two had undetectable minimal residual disease by flow cytometry (<0.01%). Five patients were subsequently treated with a stem cell transplant. All eight patients that achieved CR or CRi eventually relapsed. One patient remains alive following treatment with tisagenlecleucel after relapse. Grade 3 or higher infections occurred in four out of 10 patients, and other toxicities commonly associated with bortezomib were not seen.ConclusionsIn children with relapsed or refractory ALL, the addition of bortezomib to reinduction chemotherapy that includes mitoxantrone produces a complete response in the majority of cases and does not lead to excessive toxicity.

show abstract

Bortezomib-induced severe pulmonary complications in multiple myeloma: A case report and literature review

Cited by 13 publications

References 15 publications

Phase 1 study of the protein deubiquitinase inhibitor VLX1570 in patients with relapsed and/or refractory multiple myeloma

Phase 1 study of the protein deubiquitinase inhibitor VLX1570 in patients with relapsed and/or refractory multiple myeloma

Secondary lymphoblastic leukemia occurring 38 months after the primary diagnosis of multiple myeloma: A case report

Treatment of children with relapsed and refractory acute lymphoblastic leukemia with mitoxantrone, vincristine, pegaspargase, dexamethasone, and bortezomib

Contact Info

Product

Resources

About