Research includes phase III bone marrow transplant study presented as first abstract in the scientific plenary session
Researchers from the John Theurer Cancer Center at Hackensack University Medical Center, one of the nation's top 50 best hospitals for cancer, presented results from 31 major studies of blood-related cancers - leukemia, lymphoma and multiple myeloma -- during the American Society of Hematology (ASH) Annual Meeting, December 10-13, 2011 in San Diego.
Research highlights from the John Theurer Cancer Center included a global clinical trial of a new type of medication (HDAC inhibitor) against relapsed multiple myeloma led at the John Theurer Cancer Center; an examination of treatment outcomes for more than 900 lymphoma patients who received stem cell transplants at the John Theurer Cancer Center; an analysis of Phase III data for a new cancer drug as it applies to older chronic myeloid leukemia patients; results from a Phase III, 50-center study of stem cell versus bone marrow transplantation for high-risk leukemia patients; a laboratory analysis of a gene-encoded protein that may have a protective role in difficult-to-treat mantle cell lymphoma; and a comparison study of the best transplant options for myeloma patients who relapse after autologous stem cell transplantation.
"The American Society of Hematology meeting is where the most important advances in therapies for difficult-to-treat blood-related cancers are announced," said Andre Goy, M.D., M.S., Chairman and Director, Chief of Lymphoma, and Director, Clinical and Translational Cancer Research, John Theurer Cancer Center. "Our extensive involvement in the ASH meeting is indicative of the major role we play in cancer research not just here in the U.S., but around the world."
ASH is the world's largest professional society concerned with the causes and treatment of blood disorders. More than half of the John Theurer Cancer Center presentations showcased at the ASH Annual Meeting had been considered exceptionally significant and were presented orally, including Phase I and Phase II studies, multi-center, international trials in collaboration with leading cancer institutions.
"We are proud to make such a significant contribution to advancing the treatment of hematologic cancers, and to lead or participate in so many global clinical studies alongside leading cancer institutions such as the National Cancer Institute, Mayo Clinic, MD Anderson and Dana-Farber," said Andrew L. Pecora, M.D., F.A.C.P., C.P.E., Chief Innovations Officer and Professor and Vice President of Cancer Services, John Theurer Cancer Center. "We are especially happy that our leadership in cancer research translates into early access to promising treatments for our patients, and major advances in care for all who have cancer."
For a complete list of abstracts presented by the John Theurer Cancer Center, visit jtcancercenter.org/ASH2011. Highlights of the John Theurer Cancer Center presentations include:
Results of a Phase III Prospective, Randomized Trial of Filgrastim-Mobilized Peripheral Blood Stem Cells Compared to Bone Marrow Transplants from Unrelated Donors. (Abstract number 1; oral presentation, plenary scientific session, December 11, 2:05 p.m.)
As part of a 50-center study by the Blood and Marrow Transplant Clinical Trials Network, Scott D. Rowley, M.D., Chief, Blood and Marrow Stem Cell Transplantation, led the John Theurer Cancer Center arm of a Phase III randomized, multi-center trial of unrelated donor peripheral blood stem cell vs. bone marrow transplantation for patients with high-risk leukemia.
The purpose of the NIH-funded study was to examine both two-year survival and the incidence of graft-versus-host disease (GVHD). GVHD is a condition in which the transplanted cells attack the patient's body after a transplant.
Previous randomized trials showed that high-risk leukemia patients receiving peripheral stem cell transplants activated by filgrastim, an infection-fighting drug that helps in gathering stem cells, had better engraftment (acceptance of the cells by their body's bone marrow) than patients who received bone marrow transplants from siblings with identical human leukocyte antigens (HLA, a type of blood protein). The stem cell patients had increased risks of acute and chronic GVHD, but decreased incidence of relapse as well as improved survival. Retrospective studies, however, did not show the same protective effect from stem cells.
In the current study, 551 patients were randomized to receive either an unrelated donor peripheral blood stem cell transplant or bone marrow transplant. At two years post-treatment, there were no significant differences in patient survival between the study arms. Patients who received stem cells, however, had a higher incidence of chronic GVHD.
Final Result of a Global Phase IIB Trial of Vorinostat with Bortezomib in Patients with Relapsed Multiple Myeloma. (Abstract number 480; oral presentation, December 12, 11:45 a.m.)
David S. Siegel, M.D., Ph.D., Chief of Multiple Myeloma at the John Theurer Cancer Center, led a global Phase IIB clinical trial of vorinostat (Zolinza), a medication that is already approved to treat cutaneous T-cell lymphoma, against multiple myeloma. Dr. Siegel previously led other studies of vorinostat, which is a histone deacetylase (HDAC) inhibitor, the first in a class of drugs that regulate enzymes involved in cell signaling.
In the current study, Dr. Siegel and colleagues conducted an open label, single-arm (all patients received the same study medications) Phase IIB trial of vorinostat plus bortezomib for multiple myeloma patients unresponsive to bortezomib or unresponsive, intolerant, or ineligible for immunomodulatory therapies. All study participants had received two or more prior anti-myeloma treatments, and relapsed or progressed following earlier systemic therapy. One hundred forty-three patients, who had myeloma for a median of 4.6 years, were enrolled from 41 centers in 12 countries.
All patients in the study received 21-day cycles of bortezomib administered intravenously on days 1,4,8 and 11 plus oral vorinostat (400 mg) on days one to 14. If a patient had no change after four treatment cycles, or progressive disease after two cycles, oral dexamethasone (20 mg) was added for subsequent cycles.
The researchers concluded that the combination of vorinostat and bortezomib is active in patients whose disease is considered refractory to prior bortezomib and immunomodulatory drugs and may offer a new treatment option for heavily pretreated, double-refractory myeloma patients.
Two Decades of Stem Cell Transplantation in Lymphoma: Outcomes of 938 Transplants Performed at John Theurer Cancer Center. (Abstract number 3086; poster session, December 11, 6:00 - 8:00 p.m.)
Anthony R. Mato, M.D., Hematologist/Oncologist, Lymphoma and a team of 12 fellow researchers from the John Theurer Cancer Center conducted a retrospective cohort analysis of the survival of 938 lymphoma patients who underwent either autologous (with one's own cells) or allogeneic (with another's cells) stem cell transplants at the Theurer Center between 1990 and 2011.
While John Theurer Cancer Center physicians have used both types of transplants combined with chemotherapy for relapsed lymphoma patients, there remains little long-term follow up data for either treatment to guide clinical decision-making.
The researchers' statistical analysis revealed that patients treated with autologous stem cell transplantation had a median overall survival of 149 months, while those treated with allogeneic transplants had a median overall survival of 39 months. The donor source of stem cells (matched sibling vs. matched unrelated donor) in allogeneic transplants did not seem to affect overall survival, nor did whether the cells were from peripheral blood or bone marrow. The researchers will continue to conduct ongoing studies of whether immune-based therapies after transplantation of autologous cells improve survival.
Safety and Efficacy of Nilotinib in Older Chronic Myeloid Leukemia (CML) Patients in the Chronic Phase Compared with Younger Chronic-Phase CML Patients. (Abstract number 3768; poster session, December 12, 6:00-8:00 p.m.)
The multi-center, international Phase III study ("ENESTnd"study) comparing nilotinib (Tasigna-) with imatinib (Gleevec-) found that newly diagnosed CML patients receiving nilotinib had significantly higher levels of disease response and lower levels of disease progression. A team at the John Theurer Cancer Center, led by Stuart L. Goldberg, M.D., Chief, Leukemia, took part in the initial ENESTnd study as well as the current study.
In the new study, Dr. Goldberg and colleagues analyzed the ENESTnd data to evaluate the efficacy and safety of nilotinib (both 300 and 400 mg) for newly diagnosed CML patients, age 65+, who were in the chronic phase. Their response to treatment was compared with that of younger patients, and the drug's safety was also evaluated. The analysis covered 64 older patients who were followed a minimum of 24 months, in comparison to a much larger group of younger patients.
The study used a number of measures. One was major molecular response (MMR), which is based on a blood or bone marrow test that measures certain leukemia-related proteins, indicating a major treatment response. Complete cytogenic response (CCyR) was another measure used. The CCyR test measures levels of the Philadelphia chromosome, the abnormality that causes CML. Drug safety was also evaluated, as was progression to the "blast" phase of CML. CML has two phases: "chronic," in which it is relatively dormant, and "accelerated" or "blast," in which It is active.