Frequency, Characteristics, and Reversibility of Peripheral Neuropathy During Treatment of Advanced Multiple Myeloma With Bortezomib

Richardson, Paul G.; Briemberg, Hannah; Jagannath, Sundar; Wen, Patrick Y.; Barlogie, Bart; Berenson, James R.; Singhal, Seema; Siegel, David S.; Irwin, David; Schuster, Michael W.; Srkalović, Gordan; Alexanian, Raymond; Rajkumar, S. Vincent; Limentani, Steven; Alsina, Melissa; Orłowski, Robert Z.; Najarian, Kevin B.; Esseltine, Dixie Lee; Anderson, Kenneth C.; Amato, Anthony A.

doi:10.1200/jco.2005.04.7779

Cited by 596 publications

(519 citation statements)

References 18 publications

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“…In particular, the short duration of therapy may minimize cumulative peripheral neuropathy arising from treatment. Both bortezomib 42,43 and thalidomide [44][45][46] are associated with peripheral neuropathy, so a possible increase in the incidence of peripheral neuropathy when these agents are combined was a concern with BTD therapy. However, the 45% rate of neuropathy reported in our analysis appears similar to that reported with bortezomib plus melphalan and prednisone in previously untreated patients in the VISTA phase 3 study (44%) 4 and with single-agent bortezomib in the Assessment of Proteasome Inhibition on Extending Remissions (APEX) phase 3 study (37%) 43 ; the 9% rate of grade 3 events also appears similar to the rates reported in VISTA (13%) 4 and APEX (9%), 43 in the GIMEMA phase 3 study of BTD (9%), 13 in the IFM phase 3 study of bortezomib plus dexamethasone (7%), 38 and in phase 3 studies of thalidomide plus dexamethasone (3%-7%).…”

Section: Original Article 3148mentioning

confidence: 99%

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

Kaufman

Nooka

Vrana³

et al. 2010

Cancer

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BACKGROUND: This single-center retrospective study determined the efficacy of bortezomib, thalidomide, and dexamethasone (BTD) as induction for patients with multiple myeloma (MM) who were eligible for autologous stem cell transplantation (ASCT). METHODS: Patients with symptomatic MM who had received BTD induction before stem cell collection at Winship Cancer Institute were included. BTD induction comprised up to 8 3-week cycles of bortezomib 1.3 mg/m 2 on Days 1, 4, 8, and 11; thalidomide 100 mg daily; and dexamethasone 40 mg on Days 1 through 4 and Days 9 through 12. Stem cell mobilization involved granulocyte-colony-stimulating factor and/or cyclophosphamide. Response was assessed according to European Group for Blood and Marrow Transplantation criteria. RESULTS: Review of medical records identified 44 eligible patients (34 patients who were treated in the front-line setting and 10 patients who were treated for recurrent disease) who received a median of 4 BTD cycles. The overall response rate (ORR) was 91%, which included a greater than or equal to very good partial response (!VGPR) rate of 57% (including 20% stringent complete responses/complete response [sCR/CR] rate). In front-line patients, the ORR was 94%, which included a 56% !VGPR rate (24% sCR/CR). The median CD34-positive stem cell collection was 10.67 Â 10 6 /kg. The ORR after ASCT in 34 patients who were evaluable for response was 100%, including a 76% !VGPR rate (53% sCR/CR). Among all 44 patients, the median progression-free survival (PFS) was 27.4 months. The median overall survival (OS) was not reached after a median follow-up of 25 months, and the 2-year OS rate was 82%. There were no significant differences in PFS (27.4 months vs 23.5 months) or in 2-year survival (80% vs 90%) between patients who did and did not undergo ASCT, respectively. Twenty patients (45%) developed neuropathy, including 4 (9%) with grade 3 neuropathy episodes, and 1 patient developed deep vein thrombosis. CONCLUSIONS: BTD was highly effective and well tolerated as induction for MM patients who were eligible for ASCT. Long-term outcomes appeared to be similar with or without ASCT consolidation. Cancer 2010;116:3143-51.

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Section: Original Article 3148mentioning

confidence: 99%

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

Kaufman

Nooka

Vrana³

et al. 2010

Cancer

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“…Three proteasome inhibitors (PIs), bortezomib (BTZ: Kane et al , 2003; Richardson et al , 2003, 2005), carfilzomib (CFZ) and ixazomib (IXZ) are currently approved for the treatment of MM, with several others in development. Although important therapeutic advances, these PIs are associated with significant and dose‐limiting off‐target toxicities (Lonial et al , 2005; Richardson et al , 2006; Cai et al , 2014; Harvey, 2014; Atrash et al , 2015; Wanchoo et al , 2015) and the development of acquired resistance (Fall et al , 2014; Huber et al , 2015; Niewerth et al , 2015). Despite consistently high response rates with PI‐based combinations, almost all MM patients eventually relapse, with progressively lower rates and durations of response with each subsequent line of therapy and poor prognosis as resistance emerges (Kumar et al , 2012).…”

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confidence: 99%

Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients

Levin¹,

Spencer

Harrison

et al. 2016

Br J Haematol

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SummaryProteasome inhibitors (PIs) are highly active in multiple myeloma (MM) but resistance is commonly observed. All clinical stage PIs effectively inhibit chymotrypsin‐like (CT‐L) activity; one possible mechanism of resistance is compensatory hyperactivation of caspase‐like (C‐L) and trypsin‐like (T‐L) subunits, in response to CT‐L blockade. Marizomib (MRZ), an irreversible PI that potently inhibits all three 20S proteasome subunits with a specificity distinct from other PIs, is currently in development for treatment of MM and malignant glioma. The pan‐proteasome pharmacodynamic activity in packed whole blood and peripheral blood mononuclear cells was measured in two studies in patients with advanced solid tumours and haematological malignancies. Functional inhibition of all proteasome subunits was achieved with once‐ or twice‐weekly MRZ dosing; 100% inhibition of CT‐L was frequently achieved within one cycle at therapeutic doses. Concomitantly, C‐L and T‐L activities were either unaffected or increased, suggesting compensatory hyperactivation of these subunits. Importantly, this response was overcome by continued administration of MRZ, with robust inhibition of T‐L and C‐L (up to 80% and 50%, respectively) by the end of Cycle 2 and maintained thereafter. This enhanced proteasome inhibition was independent of tumour type and may underlie the clinical activity of MRZ in patients resistant to other PIs.

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“…3) [23], the most common adverse events for all patients with MM at the standard 1.3-mg/m 2 dose of bortezomib were asthenia (fatigue, weakness, malaise) (65%), gastrointestinal effects (nausea, 64%; diarrhea, 51%; constipation, 43%; vomiting, 36%), thrombocytopenia (43%), and PN (37%), with the latter usually being reversible [24].…”

Section: Management Of Side Effects During Bortezomib Therapymentioning

confidence: 99%

A Practical Update on the Use of Bortezomib in the Management of Multiple Myeloma

et al. 2006

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Learning ObjectivesAfter completing this course, the reader will be able to:1. Discuss clinical trial data for treatment with bortezomib monotherapy and bortezomib-based combination therapy in patients with multiple myeloma who have received at least one prior therapy.2. Discuss the management of the most common adverse events associated with bortezomib, including peripheral neuropathy and thrombocytopenia.3. Describe prognostic factors in patients with multiple myeloma who have received at least one prior therapy. Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.

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Frequency, Characteristics, and Reversibility of Peripheral Neuropathy During Treatment of Advanced Multiple Myeloma With Bortezomib

Cited by 596 publications

References 18 publications

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients

A Practical Update on the Use of Bortezomib in the Management of Multiple Myeloma

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