High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: Results of a global phase 3b expanded access program

Joseph R. Mikhael, Andrew R. Belch, H. Miles Prince, Maria Nambo Lucio, Angelo Maiolino, Alessandro Corso, Maria Teresa Petrucci, Pellegrino Musto, Mieczyslaw Komarnicki, A. Keith Stewart

Research output: Contribution to journalArticle

Abstract

Phase 2 trials have demonstrated that bortezomib ± dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open-label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a maximum of eight 3-week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after ≥2 cycles or for stable disease after ≥4 cycles. Responses were assessed based on M-protein changes. Overall response rate was 67%, including 11% complete (100% M-protein reduction), 22% very good partial (75-99% reduction), 18% partial (50-74% reduction), and 16% minimal response (25-49% reduction). Dexamethasone was added in 208 patients (33%), of whom 70 (34%) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39%), neutropenia (16%), anaemia (12%), diarrhoea (7%), and peripheral neuropathy (6%). Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalBritish Journal of Haematology
Volume144
Issue number2
DOIs
Publication statusPublished - Jan 2009

Fingerprint

Multiple Myeloma
Dexamethasone
Peripheral Nervous System Diseases
Neutropenia
Thrombocytopenia
Anemia
Diarrhea
Proteins
Bortezomib
Therapeutics

Keywords

  • Bortezomib
  • Dexamethasone
  • Expanded access
  • M-protein reduction
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology

Cite this

High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma : Results of a global phase 3b expanded access program. / Mikhael, Joseph R.; Belch, Andrew R.; Prince, H. Miles; Lucio, Maria Nambo; Maiolino, Angelo; Corso, Alessandro; Petrucci, Maria Teresa; Musto, Pellegrino; Komarnicki, Mieczyslaw; Stewart, A. Keith.

In: British Journal of Haematology, Vol. 144, No. 2, 01.2009, p. 169-175.

Research output: Contribution to journalArticle

Mikhael, Joseph R. ; Belch, Andrew R. ; Prince, H. Miles ; Lucio, Maria Nambo ; Maiolino, Angelo ; Corso, Alessandro ; Petrucci, Maria Teresa ; Musto, Pellegrino ; Komarnicki, Mieczyslaw ; Stewart, A. Keith. / High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma : Results of a global phase 3b expanded access program. In: British Journal of Haematology. 2009 ; Vol. 144, No. 2. pp. 169-175.
@article{d5ae2ed447204bd3a90efa8d4b856a75,
title = "High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: Results of a global phase 3b expanded access program",
abstract = "Phase 2 trials have demonstrated that bortezomib ± dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open-label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a maximum of eight 3-week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after ≥2 cycles or for stable disease after ≥4 cycles. Responses were assessed based on M-protein changes. Overall response rate was 67{\%}, including 11{\%} complete (100{\%} M-protein reduction), 22{\%} very good partial (75-99{\%} reduction), 18{\%} partial (50-74{\%} reduction), and 16{\%} minimal response (25-49{\%} reduction). Dexamethasone was added in 208 patients (33{\%}), of whom 70 (34{\%}) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39{\%}), neutropenia (16{\%}), anaemia (12{\%}), diarrhoea (7{\%}), and peripheral neuropathy (6{\%}). Neuropathy (any grade) was seen in 25{\%} of the patients and led to discontinuation in 5{\%}. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.",
keywords = "Bortezomib, Dexamethasone, Expanded access, M-protein reduction, Multiple myeloma",
author = "Mikhael, {Joseph R.} and Belch, {Andrew R.} and Prince, {H. Miles} and Lucio, {Maria Nambo} and Angelo Maiolino and Alessandro Corso and Petrucci, {Maria Teresa} and Pellegrino Musto and Mieczyslaw Komarnicki and Stewart, {A. Keith}",
year = "2009",
month = "1",
doi = "10.1111/j.1365-2141.2008.07409.x",
language = "English",
volume = "144",
pages = "169--175",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons, Ltd (10.1111)",
number = "2",

}

TY - JOUR

T1 - High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma

T2 - Results of a global phase 3b expanded access program

AU - Mikhael, Joseph R.

AU - Belch, Andrew R.

AU - Prince, H. Miles

AU - Lucio, Maria Nambo

AU - Maiolino, Angelo

AU - Corso, Alessandro

AU - Petrucci, Maria Teresa

AU - Musto, Pellegrino

AU - Komarnicki, Mieczyslaw

AU - Stewart, A. Keith

PY - 2009/1

Y1 - 2009/1

N2 - Phase 2 trials have demonstrated that bortezomib ± dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open-label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a maximum of eight 3-week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after ≥2 cycles or for stable disease after ≥4 cycles. Responses were assessed based on M-protein changes. Overall response rate was 67%, including 11% complete (100% M-protein reduction), 22% very good partial (75-99% reduction), 18% partial (50-74% reduction), and 16% minimal response (25-49% reduction). Dexamethasone was added in 208 patients (33%), of whom 70 (34%) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39%), neutropenia (16%), anaemia (12%), diarrhoea (7%), and peripheral neuropathy (6%). Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.

AB - Phase 2 trials have demonstrated that bortezomib ± dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open-label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a maximum of eight 3-week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after ≥2 cycles or for stable disease after ≥4 cycles. Responses were assessed based on M-protein changes. Overall response rate was 67%, including 11% complete (100% M-protein reduction), 22% very good partial (75-99% reduction), 18% partial (50-74% reduction), and 16% minimal response (25-49% reduction). Dexamethasone was added in 208 patients (33%), of whom 70 (34%) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39%), neutropenia (16%), anaemia (12%), diarrhoea (7%), and peripheral neuropathy (6%). Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.

KW - Bortezomib

KW - Dexamethasone

KW - Expanded access

KW - M-protein reduction

KW - Multiple myeloma

UR - http://www.scopus.com/inward/record.url?scp=58149086029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149086029&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2141.2008.07409.x

DO - 10.1111/j.1365-2141.2008.07409.x

M3 - Article

C2 - 19036114

AN - SCOPUS:58149086029

VL - 144

SP - 169

EP - 175

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -