Bortezomib retreatment for relapsed and refractory multiple myeloma in real‐world clinical practice

Hulin, Cyrille; Rubia, Javier de la; Dimopoulos, Meletios A.; Terpos, Evangelos; Katodritou, Eirini; Hungria, Vania T.M.; Samblanx, Hadewijch De; Stoppa, Anne‐Marie; Aagesen, Jesper; Sargın, Deniz; Sioni, Anastasia; Belch, Andrew; Diels, Joris; Olie, Robert A.; Robinson, Don; Potamianou, Anna; Velde, Helgi van de; Delforge, Michel

doi:10.1002/hsr2.104

Cited by 21 publications

(15 citation statements)

References 44 publications

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“…Similarly, no evidence of new cumulative neurotoxicity ( NTX) was observed in prolonged therapy of up to 32 cycles or retreatment with BTZ . In fact, no apparent increase in PN incidence nor severity at BTZ retreatment vs initial BTZ treatment in a real‐world oncology practice setting is observed regardless of the timing of retreatment; however, these results may be biased due to the elimination of patients who showed the most significant problems from BIPN from their initial exposure to BTZ.…”

Section: Risk Factorsmentioning

confidence: 97%

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Velasco

Alberti

Bruna

et al. 2019

J Peripheral Nervous Sys

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Proteasome inhibitors (PIs), especially bortezomib (BTZ), have come to the forefront over the last years because of their unprecedented efficacy mainly against multiple myeloma (MM). Unfortunately, peripheral neuropathy (PN) secondary to treatment of MM with PIs has emerged as a clinically relevant complication, which negatively impacts the quality of life of MM survivors. Bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, which develops in 30% to 60% of patients during treatment. Typically, BIPN is a length-dependent sensory axonopathy characterized by numbness, tingling, and severe neuropathic pain in stocking and glove distribution. BIPN mechanisms have not yet been fully elucidated. Experimental studies suggest that aggresome formation, endoplasmic reticulum stress, myotoxicity, microtubule stabilization, inflammatory response, and DNA damage could contribute to this neurotoxicity. A new generation of structurally distinct PIs has been developed, being increasingly used in clinical settings. Carfilzomib exhibits a much lower neurotoxicity profile, with a significantly lower incidence of PN compared to BTZ. Pre-existing PN increases the risk of developing BIPN. Besides, BIPN is related to dose, schedule and mode of administration and modifications of these factors have lowered the incidence of PN. However, to date there is no cure for PIs-induced PN (PIIPN), and a careful neurological monitoring and dose adjustment is a key strategy for preserving quality of life. This review critically looks at the pathogenesis, incidence, risk factors, both clinical and pharmacogenetics, clinical phenotype and management of PIIPN. We also make recommendations for further elucidating the whole clinical spectrum of PIIPN. K E Y W O R D S bortezomib, carfilzomib, peripheral neuropathy, peripheral neurotoxicity, proteasome inhibitor-induced neuropathy 1 | INTRODUCTION Inhibition of proteasome function has emerged as an efficacious strategy with a robust rationale in anticancer therapy. Proteasome inhibitor (PI)-based regimens have become an integral component of the treatment of multiple myeloma (MM), a malignancy of plasma cells accounting for approximately 1% of cancers and 12% of hematological malignancies. Bortezomib (BTZ) was the first approved PI and to date has become the standard of anti-myeloma 1 and mantle cell lymphoma therapies. 2 Postmarketing trials of BTZ quickly pointed to PN as its main nonhematological, dose-limiting toxicity of BTZ. Similar to clinical trial results, the use of BTZ in real-world oncology practice documented that BTZ-induced peripheral neuropathy (BIPN) develops in up to 50% of BTZ-treated MM patients. 3,4 PN due to MM treatment

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Section: Risk Factorsmentioning

confidence: 97%

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Velasco

Alberti

Bruna

et al. 2019

J Peripheral Nervous Sys

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“…Based on current literature review, there is much focus on the use of second-generation drugs in the treatment of relapse or refractory MM patients. Not much has been done concerning how different treatment intervals affect the prognosis of MM patients [8, 9].…”

Section: Discussionmentioning

confidence: 99%

Impact of Extended Treatment Interval on the Prognosis of Multiple Myeloma Patients: A Retrospective Study

Sun¹,

Ye²,

Mao³

et al. 2020

Oncol Res Treat

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Introduction: Recently, treatment with proteasome inhibitors and immunomodulators has improved the prognosis of multiple myeloma (MM). However, in a complex real-world situation, the patient’s ability to undergo regular and timely treatment as prescribed in clinical trials has not been studied, as well as the impact of extended treatment intervals due to different reasons. This study aimed to evaluate the treatment interval and clinical characteristics of 122 patients with primary myeloma in our hospital and explore the prognostic effects of different treatment intervals. Methods: In total, 122 patients with MM were analyzed retrospectively in our hospital from January 2007 to June 2018. The clinical and laboratory data (such as age, International Staging System [ISS] stage, chromosome, etc.) and subsequent treatment intervals were analyzed. The Cox proportional hazard regression model was used for univariate and multivariate analyses of overall survival (OS) and progression-free survival. The Kaplan-Meier method was used in survival analysis, and the log-rank test was used to test survival difference. p < 0.05 was considered to indicate statistical significance. Results: We found that prolonging the interval treatments (>28 days) shortened the OS in the younger and high-risk subgroups. On the contrary, the OS of the older and low-risk subgroups was not shortened. OS was also shortened in patients who were suitable for transplantation but did not receive a transplant. Univariate and multivariate analyses showed that extension of treatment interval was a risk factor for OS shortening. In addition, prolonged treatment interval was due to iatrogenic and family reasons. Conclusion: Extended treatment interval is unfavorable in young and high-risk MM patients and those suitable for transplantation but who did not receive a transplant. However, it has a faint impact on the elderly and low-risk subgroups.

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“…Unfortunately, in this analysis there is no evidence about number of bortezomib refractory patients before retreatment. [17].…”

Section: Discussionmentioning

confidence: 99%

“…Average ORR was 39.1% and pooled, weighted average median TTP and OS were 7.5 and 16.6 months, respectively [16]. Another large multi-centric international analysis was recently published by Hulin et al [17].…”

mentioning

confidence: 98%

Bortezomib retreatment is effective in relapsed multiple myeloma patients – real-life clinical practice data

Štork¹,

Ševčı́ková²,

Brožová³

et al. 2020

neo

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Nowadays, bortezomib, a proteasome inhibitor, is widely used in treatment of newly diagnosed or relapsed multiple myeloma. The aim of this study was to analyze efficiency of bortezomib retreatment in patients with relapsed or refractory multiple myeloma. From 2004 to 2016, 283 patients were retrospectively evaluated at all hematological centers in the Czech Republic. Bortezomib was administered at the standard dosing and in combined therapy with corticosteroids, chemotherapy or thalidomide. Before bortezomib retreatment, 61% of patients received previous lenalidomide treatment, 40.6% autologous transplantation, and median number of prior lines of therapy was three. In total, 21% of patients were refractory to the first bortezomib treatment. In bortezomib retreatment, overall response rate was 34.5%, median progression-free survival was 7.8 months (95% CI: 6.7-8.9), median duration of response was 10.5 months (95% CI: 8.0-13.0) and median overall survival was 20.3 months (95% CI: 17.9-22.7). Grade 3-4 adverse events included thrombocytopenia, neutropenia, anemia and infection. Neuropathy grade 2 or higher occurred in 19.4% of patients. We conclude that bortezomib retreatment is an effective and safe therapeutic alternative for relapsed or refractory multiple myeloma patients.

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Bortezomib retreatment for relapsed and refractory multiple myeloma in real‐world clinical practice

Cited by 21 publications

References 44 publications

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Impact of Extended Treatment Interval on the Prognosis of Multiple Myeloma Patients: A Retrospective Study

Bortezomib retreatment is effective in relapsed multiple myeloma patients – real-life clinical practice data

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