Wednesday, February 8, 2023
San Diego, California, played host to the American Society of Hematology (ASH) 53rd Annual Meeting from December 10 to 13, 2011. This year's conference featured some new drugs, some findings that might breathe new life into an old drug, and some long-term data that might help end a long-standing debate.
Key study findings included:
• Positive results with chemotherapy alone in limited-stage Hodgkin's disease
• Retreatment preferable to maintenance in low-burden follicular lymphoma
• Long-term health problems after hematopoietic cell transplant
• Peripheral blood stem cell transplants are not better than bone marrow
Long-Term Data Support Chemotherapy Alone in Hodgkin's Lymphoma
New long-term data have shifted the debate about the best treatment for patients with limited-stage Hodgkin's disease in favor of chemotherapy alone, and have highlighted the risk for late complications from radiotherapy. Lead investigator Ralph Meyer, MD, from Queen's University, Kingston, Ontario, Canada, reported that chemotherapy alone was associated with higher overall survival when compared with radiation with or without chemotherapy (94% vs 87% of patients were still alive at 12 years). The main reason was fewer deaths from causes other than Hodgkin's lymphoma, including secondary cancers and cardiovascular events. In the long term, patients with limited-stage Hodgkin's lymphoma "may be better served" with chemotherapy without radiation, Dr. Meyer concluded.
Less Is More for Rituximab in Low-Burden Follicular Lymphoma
For patients with low-tumor-burden follicular lymphoma in whom treatment with rituximab (Rituxan, Genentech) is being considered, a retreatment strategy is preferable to maintenance therapy, according to Brad Kahl, MD, assistant professor of medicine at the University of Wisconsin–Madison. Outcomes with rituximab given only on disease progression (the retreatment strategy) were similar to those seen when rituximab was given as maintenance therapy, but the retreatment strategy requires nearly 4 times less drug, Dr. Kahl noted. "We believe the retreatment strategy is the preferred option to help patients with low-tumor-burden follicular lymphoma manage their disease," he said.
First Study Ever of Long-Term Problems After Hematopoietic Cell Transplant
Hematopoietic cell transplant offers the only potential for a cure for many hematological cancers, but recipients remain at risk for psychological and chronic health conditions years later, according to a new long-term study. "It's important to realize that once a transplant is over, it's not really over," said Stephanie J. Lee, MD, MPH, from the University of Washington School of Medicine in Seattle, who was not involved in the study. Commonly seen conditions included myocardial infarction, stroke, blindness, diabetes, musculoskeletal problems, and subsequent malignancies. The study's senior author, Smita Bhatia, MD, MPH, from City of Hope in Duarte, California, said transplant patients need aggressive long-term follow-up.
Transplants With PBSCs Not Better Than Bone Marrow
The use of peripheral blood stem cells (PBSCs) has increased to 75% of unrelated living donor transplants, but there are no real data to support this shift, Claudio Anasetti, MD, chair of the Department of Blood and Marrow Transplant at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, noted during a plenary session. Now, the first trial to compare PBSCs with bone marrow transplants from unrelated donors has found that the 2 approaches result in similar survival, but that the PBSC transplants are associated with higher rates of chronic graft-vs-host-disease (GVHD), he reported. Although engraftment is faster in patients receiving PBSCs, the incidence of overall chronic GVHD in these patients is higher than in those transplanted with bone marrow stem cells (53% vs 40%), he noted.
New Lease of Life for Gemtuzumab, Now It Shows Survival Advantage
The monoclonal antibody gemtuzumab ozogamicin (Mylotarg, Pfizer), which was voluntarily withdrawn from the market in the United States because it did not improve survival in patients with newly diagnosed acute myeloid leukemia, has now shown a survival advantage in the same type of patients in 2 separate trials. In 1 trial, headed by Sylvie Castaigne, MD, from the Hôpital de Versailles, France, adding gemtuzumab to standard chemotherapy significantly improved overall survival, as well as event-free survival, when compared with chemotherapy alone. In the other trial, the addition of gemtuzumab to induction chemotherapy did not lead to unacceptable increases in toxicity, and it both improved disease control and delivered a significant overall survival benefit for older patients.
Novel Compound Holds Promise in High-Risk Chronic Lymphocytic Leukemia
The Bruton's tyrosine kinase inhibitor PCI 32765 from Pharmacyclics showed high rates of progression-free survival and low toxicity in patients with relapsed chronic lymphocytic leukemia in early clinical testing, reported Susan O'Brien, MD, professor of medicine at the University of Texas MD Anderson Cancer Center in Houston. The drug is now in a phase 3 clinical trial, but the results from the earlier studies presented at ASH have impressed experts. "I don't want to hype this, but we are hoping for a repeat of the success that was enjoyed by the poster child of targeted therapy, imatanib, for the treatment of chronic myeloid leukemia," commented ASH President J. Evan Sadler, MD, PhD.
New Insight Into Drug Action in Multiple Myeloma
Research performed at the Mayo Clinic in Scottsdale, Arizona, has provided new insight into how thalidomide (Thalomid, Celgene) and lenalidomide (Revlimid, Celgene) work in multiple myeloma, which has shed light on how patients develop resistance to these drugs and set the stage for the development of new therapies. The research centers on the recently discovered protein cereblon, which was shown to cause the birth defects resulting from thalidomide use. At ASH, Keith Stewart, MD, reported data showing that this protein is also involved in the action that these drugs have in multiple myeloma.
Massive Hunt Finds New Mutations That Drive CLL
Researchers have identified a number of mutated genes in chronic lymphocytic leukemia (CLL), which should lead to a better understanding of the mechanism of the disease. The discovery will also help to refine the molecular classification of the disease and will help physicians estimate prognosis, experts predict. The study identified 9 significantly mutated genes that occurred in 5 core signaling pathways in which the genes play established roles. Of these mutations, 5 of the mutated genes have been implicated in CLL for the first time, according to study coauthor Youzhong Wan, PhD, from the Dana-Farber Cancer Center, Boston, Massachusetts, who presented the data here.
Obinutuzumab: New Drug to Replace Rituximab?
Rituximab (Rituxan, Genentech), the only monoclonal antibody specifically targeting the CD20 protein expressed on B cells, may soon have a challenger. Obinutuzumab, also from Genentech, has the same specific action but shows less propensity for immune reactions than rituximab. Obinutuzumab is now in phase 3 clinical trials. Phase 2 studies presented this year at ASH stirred up considerable interest, particularly because preliminary results from the first head-to-head comparison with rituximab showed higher response rates with the new drug. In addition, in other phase 2 studies, obinutuzumab elicited responses in patients who were refractory to rituximab. Laurie Sehn, MD, MPH, from the University of British Columbia Center for Lymphoid Cancer in Vancouver, Canada, presented the data on obinutuzumab.
Ponatinib Helps Refractory Leukemia in Nearly Half of Patients
Early results from a phase 3 study of Ariad Pharmaceuticals Inc's leukemia drug ponatinib show it is effective in nearly half of patients who had stopped responding to currently available drugs. An interim look at the study shows that 47% of patients with chronic myeloid leukemia in chronic phase had a major response to ponatinib, meaning that at least two thirds of their bone marrow was normal. Thirty-nine percent of those patients achieved complete remission of their leukemia. Ariad plans to file for US regulatory approval of ponatinib in mid-2012.
Most New Myeloma Patients Respond to Carfilzomib in Phase 2 Trial
In a small, midstage study, Onyx Pharmaceuticals Inc's experimental drug carfilzomib produced very promising response rates when combined with Revlimid (lenalidomide; Celgene) and low-dose dexamethasone in patients with newly diagnosed multiple myeloma. Most of the 53 patients in the study responded quickly to the combination therapy and continued to improve with additional treatment cycles. "Efficacy is really truly among the best we've seen across the board among a variety of regimens with or without [bone marrow] transplant," said Andrzej Jakubowiak, MD, PhD, from the University of Chicago Medical Center in Illinois, who presented the data here.
Vorinostat Shows Activity as Salvage in Multiple Myeloma
Updated results from a phase 2b study showed that adding vorinostat (Zolinza, Merck & Co) to bortezomib (Velcade, Millennium) in patients with multiple myeloma who had failed on all therapies could recapture some responses, and new data from a phase 3 registration trial showed that adding vorinostat to bortezomib significantly improved progression-free survival. Vorinostat is a histone deacetylase inhibitor approved by the US Food and Drug Administration in 2006 for cutaneous T-cell lymphoma. The setting of relapsed/refractory multiple myeloma is a potential new indication for the drug. Meletious Dimopoulos, MD, from the University of Athens School of Medicine in Greece, presented the data here.
Genetic Profile in ALL: Should All Patients Be Screened?
New data support screening all patients newly diagnosed with acute lymphocytic leukemia (ALL) for the presence of high-risk subtypes, said Kathryn Roberts, PhD, from St. Jude Children's Research Hospital in Memphis, Tennessee. A collaborative research team identified a unique subtype of BCR-ABL-negative, high-risk B-ALL, with a deletion or mutation of IKZF1. "We refer to this new subtype as Ph-like ALL," Dr. Roberts said, and these patients have a poor outcome. Up to 15% of pediatric ALL cases can be classified as Ph-like. Identifying these patients will help characterize the genomic lesions driving a unique subtype of high-risk B-ALL and help determine who will derive the most benefit from targeted therapies, Dr. Roberts said.
Contributors
Sandy Huffaker Jr, Freelance Photographer, San Diego, California
Martha Kerr, Conference News Editor, Medscape, Arlington, Virginia
Darbe Rotach, Senior Photo Editor, Medscape, New York City
Zosia Chustecka, Medscape Oncology News Editor, London, England
Roxanne Nelson, Staff Journalist, Medscape Oncology, Bellingham, Washington
Megan Brooks, Freelance Journalist, Weston, Connecticut
None of the contributors have disclosed relevant financial relationships.
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