POMALIDOMIDE, BORTEZOMIB, AND LOW-DOSE DEXAMETHASONE IN PROTEASOME INHIBITOR–EXPOSED AND LENALIDOMIDE-REFRACTORY MYELOMA: RESULTS OF A MULTICENTER, DOSE-ESCALATION, PHASE 1 TRIAL (MM-005)
Author(s): ,
Paul G Richardson
Affiliations:
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School,Boston, MA,United States
,
Craig C Hofmeister
Affiliations:
Department of Internal Medicine, Division of Hematology, The Ohio State University,Columbus, OH,United States
,
Noopur S Raje
Affiliations:
Massachusetts General Hospital,Boston, MA,United States
,
David S Siegel
Affiliations:
John Theurer Cancer Center, Hackensack University Medical Center,Hackensack, NJ,United States
,
Sagar Lonial
Affiliations:
Division of BMT, Emory University, Winship Cancer Institute-Hematology and Medical Oncology,Atlanta, GA,United States
,
Jacob Laubach
Affiliations:
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School,Boston, MA,United States
,
Yvonne A Efebera
Affiliations:
Department of Internal Medicine, Division of Hematology, The Ohio State University,Columbus, OH,United States
,
David H Vesole
Affiliations:
John Theurer Cancer Center, Hackensack University Medical Center,Hackensack, NJ,United States
,
Ajay K Nooka
Affiliations:
Division of BMT, Emory University, Winship Cancer Institute-Hematology and Medical Oncology,Atlanta, GA,United States
,
Jacalyn Rosenblatt
Affiliations:
Beth Israel Deaconess Medical Center, Harvard Medical School,Boston, MA,United States
,
Mohamed H Zaki
Affiliations:
Celgene Corporation,Summit, NJ,United States
,
Amine Bensmaine
Affiliations:
Celgene Corporation,Summit, NJ,United States
,
Jennifer Herring
Affiliations:
Celgene Corporation,Summit, NJ,United States
,
Yan Li
Affiliations:
Celgene Corporation,Summit, NJ,United States
,
Sheetal Shah
Affiliations:
Celgene Corporation,Summit, NJ,United States
,
Min S Chen
Affiliations:
Celgene Corporation,Summit, NJ,United States
Kenneth C Anderson
Affiliations:
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School,Boston, MA,United States
EHA Learning Center. Richardson P. Jun 11, 2016; 133541
Dr. Paul Richardson
Dr. Paul Richardson

Access to EHA Members only content is an EHA membership benefit. Click here to join EHA or renew your membership here.


Abstract
Discussion Forum (0)
Rate & Comment (0)
Abstract: P653

Type: Poster Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 17:30 - 19:00

Location: Poster area (Hall H)

Background
The combination of an immunomodulatory drug with the proteasome inhibitor (PI) bortezomib (BORT) and low-dose dexamethasone (LoDEX) has demonstrated preclinical synergy and considerable clinical activity in relapsed and refractory multiple myeloma (RRMM) (Mitsiades et al, Blood, 2002;99:4525-30; Richardson et al, Blood, 2014;123:1461-9). Treatment (Tx) with pomalidomide (POM) + LoDEX has been shown to delay disease progression and extend survival in patients (pts) with myeloma previously treated with lenalidomide (LEN) and BORT (Richardson et al, Blood, 2014;123:1826-32; San Miguel et al, Lancet Oncol, 2013;14:1055-66). Preliminary results of MM-005 showed that POM + BORT + LoDEX (PVd) was effective and well tolerated in LEN-refractory and BORT-exposed pts. Previously, subcutaneous (SC) BORT demonstrated non-inferiority to intravenous (IV) BORT and an improved safety profile in pts with RRMM (Moreau et al, Lancet Oncol, 2011;12:431-40). Thus, MM-005 included a cohort that received PVd with SC BORT. 

Aims
To identify the optimal dose of PVd for a phase 3 trial in pts with RRMM, to assess the efficacy and safety of PVd, and to evaluate SC administration of BORT within the PVd regimen. 

Methods
Pts must have provided informed consent and received 1-4 lines of prior Tx, with ≥ 2 consecutive cycles of LEN plus a PI. Pts had to be PI exposed and refractory to LEN but not to BORT. A 3 + 3 design with 21-day cycles was used to determine the maximum tolerated dose (MTD). In cycles 1-8, dose-escalation cohorts received POM (1-4 mg/day on days 1-14), IV or SC BORT (1-1.3 mg/m2 on days 1, 4, 8, and 11), and LoDEX (20 mg/day, or 10 mg/day for pts aged > 75 years, on days 1, 2, 4, 5, 8, 9, 11, and 12) until progressive disease (PD) or unacceptable adverse event (AE). After cycle 8, BORT was given on days 1 and 8, and LoDEX was given on days 1, 2, 8, and 9. The primary endpoint was MTD.  

Results
Of the 34 pts enrolled, 59% were male, and median age was 58.5 years (range, 36-76 years). The median number of prior anti-myeloma Tx lines was 2 (range, 1-4). All pts were refractory to LEN, and all were exposed to prior PI (97% received prior BORT and 6% received prior ixazomib). All pts discontinued Tx, mostly due to PD (n = 23) but none due to Tx-related AEs. No dose-limiting toxicities were reported in the dose-escalation cohorts or at the maximum planned dose (MPD) of POM 4 mg, BORT 1.3 mg/m2, and LoDEX 20 mg (10 mg for pts aged > 75 years). The median number of Tx cycles received was 9 (range, 2-36) for all pts and, in the MPD cohorts, was 11 (range, 2-19) with IV BORT (n = 10) vs 8 (range, 3-15) with SC BORT (n = 12). The overall response rate (≥ partial response [PR]) for all pts was 65% (n = 22), with 2 complete responses (CRs), 1 stringent CR, 11 very good PRs, and 8 PRs; median duration of response was 7.4 months. All pts achieved at least stable disease. In the MPD cohorts, grade 3/4 AEs were more frequent with IV BORT vs SC BORT (90% vs 75%), including neutropenia (80% vs 25%), thrombocytopenia (40% vs 17%), and pneumonia (30% vs 8%). There were no reports of grade 3/4 peripheral neuropathy (PN) or deep vein thrombosis (DVT).

Conclusion
PVd was highly effective in pts with LEN-refractory and PI-exposed myeloma. PVd was well tolerated, with no grade 3/4 PN or DVT and no Tx discontinuation due to Tx-related AE. AEs were generally less frequent with SC vs IV BORT. Thus, the favorable tolerability and efficacy of PVd, a potential new therapeutic option in pts with RRMM, is being further evaluated in a large phase 3 trial (MM-007).

Session topic: Innovative therapies for MM 3
Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings