Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study

Moreau, Philippe; Pylypenko, Halyna; Grosicki, Sebastian; Karamanesht, Ievgenii; Leleu, Xavier; Grishunina, Maria; Rekhtman, Grigoriy; Masliak, Zvenyslava; Robak, Tadeusz; Shubina, A.V.; Arnulf, Bertrand; Kropff, Martin; Cavet, James; Esseltine, Dixie‐Lee; Feng, Huaibao; Girgis, Suzette; Velde, Helgi van de; Deraedt, William; Harousseau, Jean‐Luc

doi:10.1016/s1470-2045(11)70081-x

Cited by 832 publications

(665 citation statements)

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“…The neuropathy with bortezomib can occur abruptly, and can be significantly painful and debilitating in a subset of patients. Recent studies show that the neurotoxicity of bortezomib can be greatly diminished by administering bortezomib using a once-weekly schedule [65,66], and by administering the drug subcutaneously [67]. Unlike lenalidomide, bortezomib does not appear to have any adverse effect on stem cell mobilization [68].…”

Section: Risk-adapted Therapymentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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Disease overviewMultiple myeloma accounts for approximately 10% of hematologic malignancies.DiagnosisThe diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. In addition, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma regardless of the presence or absence of end‐organ damage.Risk stratificationIn the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk.Risk‐adapted initial therapyStandard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard‐risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients are not candidates for transplant, initial therapy is given for approximately 12–18 months.Maintenance therapyAfter initial therapy, lenalidomide maintenance is considered for standard‐risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in pateints with intermediate or high‐risk myeloma.Management of refractory diseasePatients with indolent relapse can be treated first with two‐drug or three‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 88:225–235, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Risk-adapted Therapymentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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“…[10], [13] and [44] Recently, a phase III study showed that the subcutaneous administration of bortezomib significantly reduced the rate of all grades PN and grade ≥ 3 PN in comparison with the intravenous administration, without negatively affecting responses and survival. 51 When grade 1 PN without pain occurs, bortezomib dose should be decreased by one dose level or the schedule changed from twice-to once-weekly administration; if PN occurs during once-weekly bortezomib, the dose should be reduced by one dose level. In case of grade 2 PN, bortezomib dose should be decreased or changed to once-weekly administration; for patients receiving once-weekly bortezomib, dose reduction or temporary interruption should be considered.…”

Section: Peripheral Neuropathymentioning

confidence: 99%

Management of older adults with multiple myeloma

Palumbo¹,

Mina²

2013

Blood Reviews

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Two-thirds of patients with multiple myeloma are aged 65 years or more and the prevalence of multiple myeloma in elderly patients is expected to rise in the next future. Patients older than 65 years are usually considered ineligible for transplantation. The introduction of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, combined with conventional chemotherapy, has radically changed the treatment paradigm of elderly patients and improved outcome. A sequential approach, consisting of an induction regimen associated with a high rate of complete response, followed by consolidation/maintenance therapy, induces a profound cytoreduction and delays relapse, thus improving survival. Novel agents associated with reduced-intensity autologous transplant showed to be safe and effective in fit elderly patients. Patients older than 75 years or vulnerable ones are more susceptible to adverse events that negatively affect treatment adherence and outcome. In this setting, less toxic regimens and appropriate dose reductions should be adopted. Here we provide an overview of novel agent-based treatment strategies for elderly patients with multiple myeloma.

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“…Studies have shown that administering bortezomib once weekly instead of twice weekly reduces gastrointestinal and neuropathic toxicity by roughly 30%, 47 and subcutaneous instead of intravenous administration similarly reduces toxicity. 48 Neither modification detracts from bortezomib's overall treatment efficacy, and decisions about dosing are usually determined by the patient's health status and disease characteristics. Providers and nurses need to routinely assess side effects and aggressively modify doses if such toxicity appears to a substantial degree.…”

Section: Side Effects and Supportive Carementioning

confidence: 99%