Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis

Results of a phase 1 dose-escalation study

Donna E. Reece, Vaishali Sanchorawala, Ute Hegenbart, Giampaolo Merlini, Giovanni Palladini, Jean Paul Fermand, Robert A. Vescio, Xiangyang Liu, Yusri A. Elsayed, Andrew Cakana, Raymond L. Comenzo

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

New treatment options are required for primary systemic AL amyloidosis (AL). This phase 1 dose-escalation component of a phase 1/2 study in relapsed AL aimed to determine the maximum tolerated dose (MTD) of bortezomib once weekly (0.7-1.6 mg/m2; days 1, 8, 15, and 22; 35-day cycles) and twice weekly (0.7-1.3 mg/m2; days 1, 4, 8, and 11; 21-day cycles) and assess preliminary hematologic responses. Thirty-one patients with relapsed AL were enrolled across 7 cohorts. Dose-limiting toxicity included grade 3 congestive heart failure in 2 patients (1 at once weekly, 1.6 mg/m2, and 1 at twice weekly, 1.0 mg/m2). MTD was not defined for either schedule; the maximum doses of 1.6 mg/m2(once weekly) and 1.3 mg/m2 (twice weekly) are being used in phase 2 evaluation. Most commonly reported toxicities on both schedules included gastrointestinal events, fatigue, and nervous system disorders. Discontinuations and dose reductions for toxicity were reported in 12 and 4 patients, respectively. No treatment-related deaths occurred. Hematologic responses occurred in 15 (50%) of 30 evaluable patients, including 6 (20%) complete responses. Median time to first response was 1.2 months. Once-weekly and twice-weekly bortezomib appear generally well tolerated in relapsed AL, with promising hematologic responses. This study is registered with http://ClinicalTrials.gov under identifier NCT00298766.

Original languageEnglish
Pages (from-to)1489-1497
Number of pages9
JournalBlood
Volume114
Issue number8
DOIs
Publication statusPublished - 2009

Fingerprint

Amyloidosis
Toxicity
Maximum Tolerated Dose
Appointments and Schedules
Neurology
Nervous System Diseases
Fatigue of materials
Fatigue
Heart Failure
Bortezomib
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis : Results of a phase 1 dose-escalation study. / Reece, Donna E.; Sanchorawala, Vaishali; Hegenbart, Ute; Merlini, Giampaolo; Palladini, Giovanni; Fermand, Jean Paul; Vescio, Robert A.; Liu, Xiangyang; Elsayed, Yusri A.; Cakana, Andrew; Comenzo, Raymond L.

In: Blood, Vol. 114, No. 8, 2009, p. 1489-1497.

Research output: Contribution to journalArticle

Reece, DE, Sanchorawala, V, Hegenbart, U, Merlini, G, Palladini, G, Fermand, JP, Vescio, RA, Liu, X, Elsayed, YA, Cakana, A & Comenzo, RL 2009, 'Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: Results of a phase 1 dose-escalation study', Blood, vol. 114, no. 8, pp. 1489-1497. https://doi.org/10.1182/blood-2009-02-203398
Reece, Donna E. ; Sanchorawala, Vaishali ; Hegenbart, Ute ; Merlini, Giampaolo ; Palladini, Giovanni ; Fermand, Jean Paul ; Vescio, Robert A. ; Liu, Xiangyang ; Elsayed, Yusri A. ; Cakana, Andrew ; Comenzo, Raymond L. / Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis : Results of a phase 1 dose-escalation study. In: Blood. 2009 ; Vol. 114, No. 8. pp. 1489-1497.
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abstract = "New treatment options are required for primary systemic AL amyloidosis (AL). This phase 1 dose-escalation component of a phase 1/2 study in relapsed AL aimed to determine the maximum tolerated dose (MTD) of bortezomib once weekly (0.7-1.6 mg/m2; days 1, 8, 15, and 22; 35-day cycles) and twice weekly (0.7-1.3 mg/m2; days 1, 4, 8, and 11; 21-day cycles) and assess preliminary hematologic responses. Thirty-one patients with relapsed AL were enrolled across 7 cohorts. Dose-limiting toxicity included grade 3 congestive heart failure in 2 patients (1 at once weekly, 1.6 mg/m2, and 1 at twice weekly, 1.0 mg/m2). MTD was not defined for either schedule; the maximum doses of 1.6 mg/m2(once weekly) and 1.3 mg/m2 (twice weekly) are being used in phase 2 evaluation. Most commonly reported toxicities on both schedules included gastrointestinal events, fatigue, and nervous system disorders. Discontinuations and dose reductions for toxicity were reported in 12 and 4 patients, respectively. No treatment-related deaths occurred. Hematologic responses occurred in 15 (50{\%}) of 30 evaluable patients, including 6 (20{\%}) complete responses. Median time to first response was 1.2 months. Once-weekly and twice-weekly bortezomib appear generally well tolerated in relapsed AL, with promising hematologic responses. This study is registered with http://ClinicalTrials.gov under identifier NCT00298766.",
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