A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107): final study results

被引：63

作者：

Spencer, Andrew ^{[1
]}

Harrison, Simon ^{[2
,3
]}

Zonder, Jeffrey ^{[4
]}

Badros, Ashraf ^{[5
]}

Laubach, Jacob ^{[6
]}

Bergin, Krystal ^{[1
]}

Khot, Amit ^{[2
]}

Zimmerman, Todd ^{[7
,9
]}

Chauhan, Dharminder ^{[6
]}

Levin, Nancy ^{[8
]}

MacLaren, Ann ^{[8
]}

Reich, Steven D. ^{[8
]}

Trikha, Mohit ^{[8
]}

Richardson, Paul ^{[6
]}

机构：

[1] Monash Univ, Alfred Hlth, Melbourne, Vic, Australia

[2] Peter MacCallum Canc Ctr, East Melbourne, Australia

[3] Univ Melbourne, Melbourne, Vic, Australia

[4] Karmanos Canc Ctr, Detroit, MI USA

[5] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA

[6] Dana Farber Canc Inst, Boston, MA 02115 USA

[7] Univ Chicago Med, Comprehens Canc Ctr, Chicago, IL USA

[8] Triphase Accelerator, San Diego, CA USA

[9] Abbvie, Mettawa, IL USA

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2018年 / 180卷 / 01期

关键词：

marizomib; proteasome inhibitor; pomalidomide; low-dose dexamethasone; relapsed/refractory multiple myeloma; PROTEASOME INHIBITOR; BORTEZOMIB; LENALIDOMIDE; CARFILZOMIB; COMBINATION; IXAZOMIB; PS-341;

D O I：

10.1111/bjh.14987

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0.3-0.5 mg/m(2)) was administered over 2h on days 1, 4, 8, 11; POM (3-4 mg) on days 1-21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle. Thirty-eight patients were enrolled that had received a median of 4 (range 1-10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose-limiting toxicities (DLTs) were observed and 0.5mg/m(2) MRZ was determined to be the RP2D. The most common treatment-related >= Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre-treated, high-risk RRMM patients.

引用

页码：41 / 51

页数：11

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