[ Visit Client Website ]

Before you can access ASH's online program, you must agree to the following:
  • Abstracts submitted to the ASH Annual Meeting are considered embargoed from the time of submission.
  • The media, companies and institutions issuing press releases, and others are required to abide by the embargo policies governing the Society’s annual meeting. Read ASH’s embargo policy for more information.
Last updated October 26, 2010. Please note that this site represents the latest program changes
and differs from the print version in some details.

94 A Phase II Study of Bortezomib (Velcade ®), Cyclophosphamide (Cytoxan®), Thalidomide (Thalomid®) and Dexamethasone as First-Line Therapy for Multiple Myeloma

Oral and Poster Abstracts
Oral Session: Myeloma Therapy: Newly Diagnosed Myeloma
Sunday, December 7, 2008: 5:15 PM
Halls B and C (Moscone Center)

William Bensinger1*, Sundar Jagannath, MD2, Robert Vescio, MD3, Elber S. Camacho, MD4, Jeffrey Lee Wolf5*, David H Irwin, MD6*, Gerardo Capo III, MD7*, Marti McKinley8*, Phyllis Potts8*, David Vesole, MD, PhD9*, Amitabha Mazumder, MD2, Dixie-Lee Esseltine, MD10, Pamela Becker1*, John Crowley, PhD11 and Brian GM Durie, MD3

1Research Center, Fred Hutchinson Cancer, Seattle, WA
2St. Vincent's Comprehensive Cancer Center, New York, NY
3Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA
4Comprehensive Cancer Center of the Desert, Palm Springs, CA
5University of California San Francisco, San Francisco, CA
6Alta Bates Summit Comprehensive Cancer Center, Berkeley, CA
7Trinitas Comprehensive Cancer Center, Elizabeth, NJ
8Research Network, Aptium Oncology, Inc., Los Angeles, CA
9Loyola University Chicago, Maywood, IL
10Millennium Pharmaceuticals, Inc., Cambridge, MA
11Cancer Research & Biostatistics, Seattle, WA

Background: This phase II trial evaluated  the response rate of  sequential  bortezomib (VELCADE®), cyclophosphamide (Cytoxan®), and dexamethasone ([VCD]; 3 cycles) followed by bortezomib, thalidomide (Thalomid®), and dexamethasone ([VTD]; 3 cycles) as first-line therapy for patients with multiple myeloma.  The primary endpoints were overall response, achievement of ³ very good partial response (VGPR), as well as assessment of safety and tolerability. 

 Methods: Patients with newly diagnosed, untreated symptomatic myeloma were eligible.  Treatment consisted of three 21-day cycles of bortezomib 1.3mg/m2 days 1, 4, 8, and 11, cyclophosphamide 300mg/m2 IV days 1 and 8 and dexamethasone 40mg p.o. or IV days 1, 2, 4, 5, 8, 9, 11, 12; followed by three 21-day cycles of bortezomib 1.0mg/m2 days 1, 4, 8, and 11; thalidomide 100 mg p.o. daily and dexamethasone same as cycles 1-3.  Patients received thrombosis prophylaxis with ASA 325mg daily during cycles 4-6.  Upon completion of the 6 cycles, patients proceeded to autologous stem cell harvest, transplant and/or maintenance therapy.  Responses were defined as a decrease in serum and/or urine monoclonal (M) protein by 50% or greater.  VGPR and other responses were as per the International Response Criteria. 
Results: This report provides results for all 44 eligible patients: median age 59 years; 68% male; 61% Stage III (D/S); documented ISS Stage II/III 59%; IgG 66%, IgA 17%; 17% light chain only.  To date the first 30 patients are fully evaluable for response with 28-day post therapy follow up.  The overall response rate (ORR; ≥PR) is 90% with 18/30 (60%) achieving CR + VGPR (CR 33%); 9/30 (30%) PR and 3/30 (10%) stable disease or not evaluable.  Overall, both components of the sequential regimen were very well tolerated.  One patient had a ruptured colonic diverticulum possibly related to dexamethasone, but recovered well and achieved VGPR on trial.  There have been 49 therapy attributed toxicity events which have required drug/schedule adjustments.   Of these, 9 events were Gd 3/4: 3 attributed to cyclophosphamide, 3 to dexamethasone, 2 attributed to bortezomib and 1 to thalidomide.  DVT occurred in one patient who was at high risk because of prior bilateral hip surgery. Fourteen patients have proceeded to successful stem cell harvest and autologous transplant.  Post transplant follow up as well as response information for all 44 patients will be presented.  

 Conclusion: This bortezomib/cyclophosphamide/dexamethasone (VCD) based combination induction therapy followed by VTD is a promising addition to the treatment armamentarium for previously untreated patients.  The response rates: ORR 90%; ³ VGPR (60%) and CR (33%) are extremely encouraging and improve over our bortezomib/dexamethasone 2-drug experience which produced 90% ³ PR and 38% ³ VGPR.  This very well tolerated new regimen is potentially an important step forward in induction therapy with presentation of more mature data.

Supported by the Aptium Oncology Research Network and a research grant from Millennium Pharmaceuticals, Inc.

Disclosures: Bensinger: Millenium: Consultancy, Honoraria, Speakers Bureau; Celgene: Research Funding, Speakers Bureau. Jagannath: Millennium Pharm: Consultancy, Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau. Irwin: Celgene: Honoraria; Millennium Pharmaceuticals: Honoraria. Vesole: Celgene: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau, Stock owner; Millennium: Speakers Bureau. Esseltine: Millennium:Takeda: Employment, Equity Ownership. Durie: Celgene: Honoraria; Millennium Pharmaceuticals: Honoraria.

*signifies non-member of ASH