Article

Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma

University of Arkansas at Little Rock, Little Rock, Arkansas, United States
Blood (Impact Factor: 10.43). 11/2005; 106(9):2977-81. DOI: 10.1182/blood-2005-02-0691
Source: PubMed

ABSTRACT Bortezomib, a potent and reversible proteasome inhibitor, affects the myeloma cell and its microenvironment, resulting in down-regulation of growth and survival signaling pathways and durable responses in patients with relapsed and refractory myeloma. Potential associations between baseline parameters and outcomes with bortezomib were explored in 202 patients who received bortezomib 1.3 mg/m2 twice weekly for 2 weeks every 3 weeks for up to 8 cycles in a phase 2 trial. Using European Group for Blood and Marrow Transplantation criteria, the response rate (complete or partial response) to bortezomib alone was 27% and was not associated with sex, race, performance status, isotype, chromosome 13 deletion, number or type of previous therapies, or concentration of hemoglobin or beta2-microglobulin. By multivariate analysis, factors associated with lower response were being age 65 or older versus younger than 65 (19% vs 32%; P < .05) and plasma-cell infiltration in bone marrow greater than 50% versus 50% or less (20% vs 35%; P < .05). Factors that may be indicative of tumor burden (bone marrow plasma-cell infiltration greater than 50%, hypoalbuminemia, thrombocytopenia) were predictive of overall survival. Chromosome 13 deletion and elevated beta2-microglobulin, generally considered poor prognostic factors, were not predictive of poor outcome with bortezomib in this study.

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    • "Overall survival (OS) in relapsed and refractory MM was 17 months (Richardson et al, 2006a). Overall survival with bortezomib was predicted by tumour burden at baseline but not by elevated b 2 -microglobulin (b2M) or chromosome 13 deletion (Richardson et al, 2005b). Combination with DEX in patients with either stable (SD) or progressive disease (PD) on bortezomib alone resulted in 11% to 18% additional responses (Richardson et al, 2003, 2005a). "
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    ABSTRACT: A phase 2 trial was performed to study the combination of bortezomib (VELCADE) with intermediate-dose dexamethasone (DEX), and continuous low-dose oral cyclophosphamide (CY) in patients with relapsed multiple myeloma (MM). Fifty-four patients with advanced MM were enroled to receive eight 3-week treatment cycles with bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11, followed by three 5-week cycles with bortezomib 1.3 mg/m(2) on days 1, 8, 15, and 22. Within all cycles, DEX 20 mg/d was given orally on the day of bortezomib injection and the day thereafter. In addition, patients received CY continuous oral treatment at a dose of 50 mg/d p.o. once daily. Fifty patients completing at least one treatment cycle were evaluable for response. Complete, partial, and minor responses occurred in 16%, 66% and 8% of patients, respectively; overall response rate 90% (efficacy analysis). Median event-free survival was 12 months, with a median overall survival of 22 months. Adverse events (AE) of grades 3 or 4 occurring in at least 10% of patients comprised leucopenia, infection, herpes zoster, thrombocytopenia, neuropathy and fatigue. Bortezomib combined with DEX and CY is a highly effective treatment for relapsed MM at an acceptable rate of grade 3/4 AE. Antiviral prophylaxis appears to be mandatory.
    British Journal of Haematology 09/2007; 138(3):330-7. DOI:10.1111/j.1365-2141.2007.06656.x · 4.96 Impact Factor
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    • "A subanalysis of the SUMMIT trial revealed that better response to bortezomib was associated with younger age (response rate 32% in patients aged <65 years vs 19% in those over 65; P<0.05), and with plasma cell infiltration in bone marrow of ≤50% (35% response rate vs 20% with >50% infiltration; P<0.05) (Richardson et al. 2005b). Evidence is emerging for the use of bortezomib in patients with relapsed or refractory myeloma in combination with melphalan Level of evidence Design Treatment and dose Outcomes Reference Response rate Response duration "
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    ABSTRACT: INTRODUCTION: Multiple myeloma is a relatively common and incurable form of hematologic malignancy for which there is currently no single standard therapy. Bortezomib inhibits the 20S proteasome involved in the degradation of intracellular proteins, induces apoptosis, reverses drug resistance in multiple myeloma cells, and influences their microenvironment by blocking cytokine circuits, cell adhesion and angiogenesis in vivo. AIMS: The objective of this review is to evaluate the evidence for the use of bortezomib in the treatment of multiple myeloma. EVIDENCE REVIEW: In patients with relapsed multiple myeloma bortezomib significantly prolongs overall survival and time to progression, and improves response rates, duration of response, and quality of life compared with oral high-dose dexamethasone. Although the incidence of grade 4 adverse events was similar, grade 3 events and herpes zoster infections occur more frequently in patients treated with bortezomib than with high-dose dexamethasone. Evidence from a pharmacoeconomic study indicates that the benefits of bortezomib compared to thalidomide plus best standard care may be achieved at a reasonable cost. CLINICAL VALUE: Bortezomib is a valuable treatment option in the management of relapsed multiple myeloma that improves survival and delays disease progression compared with oral high-dose dexamethasone treatment, albeit with an increased incidence of some adverse events such as grade 3 thrombocytopenia and neutropenia.
    Core Evidence 01/2006; 1(4):265-77.
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