Presenter: J.P. Leonard Presenter's Affiliation: Weill Medical College of Cornell University Type of Session: Scientific
Bcl-2 overexpression is involved in inhibition of apoptosis and therefore results in tumor cell growth.
Bcl-2 is highly expressed in patients with Mantle Cell lymphoma.
Bcl-2 has also been shown to be a major contributor to aquired drug resistance.
Bcl-2 antisense therapy has been shown in murine models of NHL, CLL, and myeloma to decrease the production of bcl-2.
Mantle Cell Lymphoma is a lymphoma with an aggressive course and relative refractoriness to conventional chemotherapeutic agents.
In preclinical models, Oblimersen has been shown to be synergistic to other chemotherapeutic agents including cytoxan and rituxan.
Materials and Methods
37 patients with Mantle Cell Lymphoma were enrolled
14 patients were newly diagnosed and 23 had been previously treated
The median age was 67 years
The median number of prior regimens was 2.
The starting dose was 3 mg/kg/day x 7 days every 21 days. The drug was given by continuous i.v. infusion as an outpatient with ports and infusion pumps.
Patients were treated until disease progression or a max of 6 cycles.
At the time of progression, newly diagnosed patients were switched to a combination of G3139 + R-CHOP and previously treated patients were taken off study.
Of the 25 evaluable patients, 9 were newly diagnosed and 16 were relapsed.
Overall, there seemed to be two cohorts of patients. Those who relapsed in the first 3 cycles of treatment and those that were able to complete the fully planned 6 cycles without progression.
Overall roughly 40-50% of patients were able to complete the planned 6 cycles.
All toxicities were grade 1 and 2 only.
The most common of those toxicities were fatigue, cough/dyspnea, fever and nausea.
Of the previously treated patients, there was one CR with single agent Oblimersen and 6 patients with SD
Oblimersen is well tolerated, and safe in this population of newly diagnosed mantle cell lymphoma patients as well as in those who have had prior treatment for their disease.
As a single agent, Oblimersen acheives 40% SD rate
Oblimersen can be safely added to R-CHOP chemotherapy.
Mantle Cell Lymphoma is a challenging lymphoma to treat with relatively poor long term results with standard chemotherapy regimens.
Oblimersen, with it's unique mechanism of action, is an ideal candidate for use in mantle cell lymphoma were Bcl-2 is overexpressed.
These preliminary data are intriguing and further studies looking at Oblimersen alone and in combination with chemotherapy are anxiously awaited in order to define its role in the treatment of this challenging malignancy.
Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.
Aug 9, 2012 - In older patients with mantle-cell lymphoma, a rituximab-based chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by maintenance therapy with rituximab improves survival, according to a study published in the Aug. 9 issue of the New England Journal of Medicine.