Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2017 Dec;31(12):2695-2701.
doi: 10.1038/leu.2017.173. Epub 2017 Jun 2.

Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma

P G Richardson  1 , C C Hofmeister  2 , N S Raje  3 , D S Siegel  4 , S Lonial  5 , J Laubach  1 , Y A Efebera  2 , D H Vesole  4 , A K Nooka  5 , J Rosenblatt  6 , D Doss  1 , M H Zaki  7 , A Bensmaine  7 , J Herring  7 , Y Li  7 , L Watkins  7 , M S Chen  7 , K C Anderson  1
Affiliations
Clinical Trial

Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma

P G Richardson et al. Leukemia. 2017 Dec.

Erratum in

Abstract

This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m2 days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort. Patients received a median of 2 prior lines of therapy; 97% bortezomib exposed. With no dose-limiting toxicities, MTD was defined as the maximum planned dose: pomalidomide 4 mg, bortezomib 1.3 mg/m2 and LoDEX. All patients discontinued treatment by data cutoff (2 April 2015). The most common grade 3/4 treatment-emergent adverse events were neutropenia (44%) and thrombocytopenia (26%), which occurred more frequently with IV than SC bortezomib. No grade 3/4 peripheral neuropathy or deep vein thrombosis was reported. Overall response rate was 65%. Median duration of response was 7.4 months. Pomalidomide, bortezomib and LoDEX was well tolerated and effective in lenalidomide-refractory and bortezomib-exposed patients with RRMM.

Trial registration: ClinicalTrials.gov NCT01734928.

PubMed Disclaimer

Conflict of interest statement

PGR has served on advisory committees for Celgene, Novartis, Millennium and Takeda. CCH, YAE and JR have nothing to disclose. NSR has served as a consultant for Celgene, Takeda, Bristol-Myers Squibb, Amgen, Onyx, Millennium and Novartis and has received research funding from AstraZeneca, Eli Lilly and Acetylon. DSS has served on speakers bureaus for Celgene, Amgen, Takeda, Novartis and Merck. SL has served as a consultant for and received research funding from Celgene, Millennium, Novartis, Bristol-Myers Squibb, Onyx and Janssen. JL has received research funding from Celgene, Onyx, Millennium and Novartis. DHV has served on speakers bureaus for Celgene and has received research funding from Idera Pharmaceuticals. AKN has served as a consultant for Onyx and Spectrum Pharmaceuticals. DD has served on speakers bureaus for Celgene and Takeda. MHZ, YL and MSC are employees of and hold equity ownership in Celgene. AB, JH and LW are employees of Celgene. KCA has served as a consultant for Celgene, Millennium, Bristol-Myers Squibb and Gilead and has equity ownership in Acetylon and Oncocorp.

Figures

Figure 1
Figure 1
MM-005 trial design. MM-005 included 5 dose-escalation cohorts. Three patients were treated at each dose level, and 7 additional patients were treated at the MTD in the expansion phase of the trial. An additional cohort of patients treated with SC bortezomib (BORT) was included (n=12). Patients were evaluated every 21 days until treatment discontinuation. Patients will undergo long-term follow-up for OS and secondary primary malignancies (SPM). *For cycles 1–8, then D1 and D8 for cycle ⩾9. †For cycles 1–8, then D1–2 and D8–9 for cycles ⩾9. ‡10 mg for patients aged >75 years. POM, pomalidomide.
Figure 2
Figure 2
Response outcomes. All treated patients were evaluated for response (better than or equal to PR). TTR and DOR were reported for patients who achieved response. BORT, bortezomib; CR, complete response; sCR, stringent complete response; VGPR, very good PR.
See this image and copyright information in PMC

References

    1. Cornell RF, Kassim AA. Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity. Bone Marrow Transplant 2016; 51: 479–491. - PMC - PubMed
    1. Ria R, Reale A, Vacca A. Novel agents and new therapeutic approaches for treatment of multiple myeloma. World J Methodol 2014; 4: 73–90. - PMC - PubMed
    1. Kumar SK, Therneau TM, Gertz MA, Lacy MQ, Dispenzieri A, Rajkumar SV et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc 2004; 79: 867–874. - PubMed
    1. Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai Y et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000; 96: 2943–2950. - PubMed
    1. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002; 99: 4525–4530. - PubMed

Publication types

MeSH terms

Associated data