Heart Failure with Carfilzomib in Patients with Multiple Myeloma: A Meta-analysis of Randomized Controlled Trials

Rahman, M Rubayat; Ball, Somedeb; Paz, Pablo; Elmassry, Mohamed; Vutthikraivit, Wasawat; Bandyopadhyay, Dhrubajyoti; Lavie, Carl J.; Fonarow, Gregg C.

doi:10.1016/j.cardfail.2020.07.006

Cited by 8 publications

(5 citation statements)

References 9 publications

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“…Our results are consistent with those reported in previous studies. [ 18 , 32 , 33 ] Cardiac failure and acute renal failure are serious concerns for patients with multiple myeloma that lead to discontinuation of therapy in a number of patients. However, the pathophysiology of carfilzomib-mediated cardiotoxicity is not clearly understood, with studies suggesting several potential mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma: A meta-analysis

Xie

Wei²,

Yang³

et al. 2022

Medicine

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Background: Multiple myeloma is a clonal disorder of malignant plasma cells that comprises approximately 10% of hematologic malignancies. The aim of this study was to investigate the efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma by performing a meta-analysis of randomized controlled trials (RCTs). Methods: Data mining was conducted in March 2022 across PubMed, EMBASE and ClinicalTrials.gov . All published RCTs which assessed efficacy and toxicity of carfilzomib-based regimens treatment for transplant-ineligible patients with newly diagnosed multiple myeloma when compared with a bortezomib-based regimens were included. Results: Our meta-analysis showed that the overall response rate (ORR) (Odds ratio = 1.33, 95% CI 1.05–1.69, P = .02) was significantly higher in the carfilzomib-based regimens group than in the bortezomib-based regimens group. However, the difference in ORR did not translate into improvements in progression-free survival (PFS), overall survival (OS) and complete response rate (CRR). Adverse events of grade 3 or worse that occurred with a higher incidence in the carfilzomib-based regimens group compared with the bortezomib-based regimens group were dyspnea, hypertension, acute kidney injury, and heart failure. Conclusions: The carfilzomib-based regimens did not improve PFS, OS and CRR compared with the bortezomib-based regimens in transplant-ineligible patients with newly diagnosed multiple myeloma, and they showed higher toxicity.

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Section: Discussionmentioning

confidence: 99%

Efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma: A meta-analysis

Xie

Wei²,

Yang³

et al. 2022

Medicine

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“…Extensive data is available regarding the cardiac toxicities expected with carfilzomib. A systematic review and meta-analysis of RCTs which had estimated the relative risk of HF with carfilzomib-based regimens in patients with MM, noted an OR of 2.34 (95% CI 1.66–3.32) for all grade and 2.69 (95% CI 1.77–4.09) for high grade cardiotoxicity, respectively [ 29 ]. The incidence rate of CV events with carfilzomib treatment has varied across trials.…”

Section: Proteasome Inhibitors (Pis)mentioning

confidence: 99%

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies

et al. 2023

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With the continuous improvement in survival of cancer patients, including those with multiple myeloma, related to the novel treatment agents and therapeutic approaches, the probability for patients to develop cardiovascular disease has significantly increased, especially in elderly patients and those with additional risk factors. Multiple myeloma is indeed a disease of the elderly population and so these patients are, solely by age, at an increased risk of cardiovascular disease. Risk factors for these events can be patient-, disease- and/or therapy-related, and they have been shown to adversely impact survival. Cardiovascular events affect around 7.5% of patients with multiple myeloma and the risk for different toxicities has considerably varied across trials depending on patients’ characteristics and treatment utilized. High grade cardiac toxicity has been reported with immunomodulatory drugs (odds ratio [OR] around 2), proteasome inhibitors (OR 1.67–2.68 depending on the specific agent, and generally higher with carfilzomib), as well as other agents. Cardiac arrhythmias have also been reported with various therapies and drug interaction plays a significant role in that setting. Comprehensive cardiac evaluation before, during and after various anti-myeloma therapy is recommended and the incorporation of surveillance strategies allows early detection and management resulting in improved outcomes of these patients. Multidisciplinary interaction including hematologists and cardio-oncologists is critical for optimal patient care.

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“…Another systematic review and a meta-analysis of randomized control trials reported a significant increased risk of heart failure in MM patients treated with carfilzomib. They analyzed reported data from randomized phase III trials involving the use of carfilzomib against MM and results indicated 8.1% occurrence of heart failure in the carfilzomib arm compared to the 3.4% in the control arm ( 116 ). Patients with coexisting cardiovascular diseases and other comorbidities are at a higher risk of developing cardiotoxicity during carfilzomib treatment which raises the need for a thorough cardiovascular risk assessment process prior to carfilzomib therapy ( 117 ).…”

Section: Carfilzomib Associated Toxicitymentioning

confidence: 99%

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma

et al. 2021

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The proteasome is crucial for the degradation of intracellular proteins and plays an important role in mediating a number of cell survival and progression events by controlling the levels of key regulatory proteins such as cyclins and caspases in both normal and tumor cells. However, compared to normal cells, cancer cells are more dependent on the ubiquitin proteasome pathway (UPP) due to the accumulation of proteins in response to uncontrolled gene transcription, allowing proteasome to become a potent therapeutic target for human cancers such as multiple myeloma (MM). Up to date, three proteasome inhibitors namely bortezomib (2003), carfilzomib (2012) and ixazomib (2015) have been approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed and/or refractory MM. This review mainly focuses on the biochemical properties, mechanism of action, toxicity profile and pivotal clinical trials related to carfilzomib, a second-generation proteasome inhibitor that binds irreversibly with proteasome to overcome the major toxicities and resistance associated with bortezomib.

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Heart Failure with Carfilzomib in Patients with Multiple Myeloma: A Meta-analysis of Randomized Controlled Trials

Cited by 8 publications

References 9 publications

Efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma: A meta-analysis

Efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma: A meta-analysis

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma

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