Navigation Links
Bortezomib shows promise in reducing GVHD and reconstituting immune system in some patients
Date:12/6/2009

NEW ORLEANSA drug that has become a mainstay of multiple myeloma treatment may outperform alternative therapies in re-establishing the immune system of patients who have received stem cell transplants from unrelated, partially matched donors, according to early clinical trial results to be presented by

Dana-Farber Cancer Institute investigators at the American Society of Hematology's (ASH) annual meeting on Sunday, Dec. 6 (Abstract 48, Ernest N. Morial Convention Center, Room 243-245, 5:45 pm CT).

The trial was designed to determine whether the drug bortezomib (trade name Velcade), when added to routine agents (tacrolimus, methotrexate), can improve control of graft-versus-host disease (GVHD) and improve immune system recovery following a transplant from a mismatched-unrelated donor. GVHD is a common and potentially severe side effect of blood-forming stem cell transplants, in which donor immune cells attack normal patient cells and tissues. GVHD is more frequent in patients receiving transplants from mismatched-unrelated donors (in comparison with matched-related donors).

Based on bortezomib's effect in preclinical models, and in multiple myeloma patients who have received donor stem cell transplants, Dana-Farber's John Koreth, MBBS, DPhil, and colleagues theorized that it could help control the overactivity of immune cells responsible for GVHD in stem cell transplant patients.

Bortezomib inhibits the activity of antigen-presenting cells, which help initiate the immune attack in GVHD, and reduces activity of an important protein called nuclear factor-B in T cells, which undertake the immune attack. In preclinical studies, bortezomib has been shown to selectively deplete T cells that can target patients' normal cells. Mouse transplant studies have shown that early administration of bortezomib protects against GVHD without reducing the transplanted stem cells' ability to settle in the bone marrow.

The new, Phase 1 clinical trial involved 23 patients who received bortezomib-based therapy (bortezomib, tacrolimus, and methotrexate) after reduced-intensity stem cell transplants from mismatched-unrelated donors. Three dosage levels of bortezomib were tested. In updated results on 35 bortezomib-based mismatched-unrelated patients reported at ASH, GVHD rates and extent of immune system reconstitution were compared with patients who had received sirolimus-based therapy (sirolimus, tacrolimus, and methotrexate) after transplants from matched-related donors, matched-unrelated donors, and mismatched-unrelated donors.

The results show that the bortezomib-based therapy was safe and had little toxicity. Transplanted stem cells took root, or "engrafted" reliably, and the rate of GVHD in the bortezomib-based mismatched-unrelated transplants was comparable to that in sirolimus-based matched-related transplants. Interestingly, immune cell reconstitution was significantly improved in the bortezomib-based patients in the early post-transplant period (3-6 months), compared with the sirolimus-based patients.

"Our results suggest that borezomib is a promising novel immunomodulatory agent in donor stem-cell transplantation," Koreth says. "A Phase 2 trial is now accruing patients to help determine its ultimate effectiveness."


'/>"/>

Contact: Teresa Herbert
teresa_herbert@dfci.harvard.edu
617-632-5653
Dana-Farber Cancer Institute
Source:Eurekalert

Related medicine news :

1. Data on VELCADE(R) (Bortezomib) for Injection Based Therapies to be Presented at the International Myeloma Workshop
2. FDA Approves VELCADE(R) (Bortezomib) for Injection for Patients with Previously Untreated Multiple Myeloma
3. Publication of Clinical Results Underscores VELCADE(R) (Bortezomib) For Injection Based Therapy As a Standard of Care In Newly Diagnosed Multiple Myeloma Patients
4. Millennium Submits sNDA for VELCADE(R) (Bortezomib) for Injection for the Treatment of Front-Line Multiple Myeloma
5. VELCADE(R) (Bortezomib) for Injection Based Therapy Produced Significant Complete Remission Rates Pre- and Post-Transplantation in IFM Phase III Front-Line Multiple Myeloma Trial
6. Phase III Trial of VELCADE(R) (Bortezomib) for Injection Showed Dramatic Fourfold Increase in Complete Remission Rates When Combined With the Most Commonly Used U.S. Regimen in Front-Line Multiple Myeloma
7. Highest Reported Complete Remission Rate of 35 Percent Achieved in a Phase III Front-Line Multiple Myeloma Trial With Velcade(R) (Bortezomib) for Injection Based Therapy
8. ZOLINZA (vorinostat) in combination with bortezomib demonstrated clinical activity
9. FDA Expands VELCADE(R) (Bortezomib) for Injection Label for Patients with Multiple Myeloma
10. New drug shows promise for those with clotting disorders: McMaster researcher
11. Congress Has Allowed Most Previous Medicare Cuts to Take Effect, New Study Shows
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/28/2017)... ... ... American Farmer proudly announces the participation of Pure Line Seeds, Inc (Pure Line ... fourth quarter 2017. American Farmer airs Tuesdays at 8:30aET on RFD-TV. , Founded in ... demand grew, the small company located in Moscow, Idaho extended its sales from Northern ...
(Date:6/28/2017)... ... June 28, 2017 , ... Designers Insurance Agency, a ... northern Virginia and DC, is announcing a cooperative charity event in conjunction with ... other disorders that lead to memory impairment. , The Insight Memory Care Center ...
(Date:6/27/2017)... ... June 27, 2017 , ... Harbour , a DAO (decentralized autonomous ... Ethereum blockchain, has released their technical specifications . , 2017 has seen an ... systematic approach for determining which offerings will garner the greatest ROI. Dean Eigenmann, Co-founder ...
(Date:6/27/2017)... ... 2017 , ... A January 18th article on medGadget reports that ... by the year 2024 according to a new report. The article also notes that ... titanium. Los Angeles area clinic Beverly Hills Periodontics & Dental Implant Center says that ...
(Date:6/27/2017)... , ... June 27, 2017 , ... ... Fabrykiewicz Scholarship Foundation Fundraiser hygiene symposium in Mystic, CT. Covering the process and ... offered their experience in these popular periodontal procedures. Drs. Toback and Urbanski practice ...
Breaking Medicine News(10 mins):
(Date:6/19/2017)... HORSHAM, Pa. , June 19, 2017  Researchers ... announced today that they will host a live, complimentary ... Perspectives from the benchtop to the real world" on ... PM EDT. This webinar will feature ... a rare look into the manipulation techniques abusers use ...
(Date:6/14/2017)... The Bio Supply Management Alliance (BSMA) has ... and the Biomedical Manufacturing Network to advance ... California by providing a platform for ... workforce development. The primary focus of this alliance is ... well as small and mid-sized biomedical companies. ...
(Date:6/11/2017)... June 10, 2017  Eli Lilly and Company (NYSE: ... Phase 3 studies of galcanezumab, an investigational treatment for ... data on several key secondary endpoints for galcanezumab compared ... these studies (EVOLVE-1, EVOLVE-2 and REGAIN) will be presented ... meeting in Boston . ...
Breaking Medicine Technology: