By Peter Martin, MD
At the plenary session of the American Society of Clinical Oncology (ASCO) on Sunday, June 3, Dr. Mattias Rummel from Germany presented updated results from a phase 3 trial initially presented at the American Society of Hematology (ASH) in 2009. The study compared bendamustine plus rituximab (BR) to CHOP chemotherapy plus rituximab (R-CHOP) in over 500 patients with indolent and mantle cell lymphoma.
Now with a median follow-up period of 45 months, the updated data were consistent with the previously reported findings. Bendamustine plus rituximab (BR) was better tolerated than R-CHOP, with significantly less neutropenia, fewer infections, and no alopecia (hair loss), and was also more effective, reducing the risk of progression roughly two-fold.
Importantly, there was no difference in the rate of transformation to aggressive lymphoma, the rate of secondary malignancies, and the ability to collect stem cells. These data support the design of ongoing and planned cooperative group trials further evaluating the first-line use of BR and BR-based combinations.
In his discussion of the abstract, Dr. Michael Williams from the University of Virginia agreed that the data were promising but cautioned that a peer-reviewed publication of the data remains to be seen.
By Peter Martin, MD
A recently published study from investigators at Stanford University and in Lund University in Sweden used data from a large Swedish cohort study, birth records, and cancer registries to look for risk factors associated with development of non-Hodgkin lymphoma (NHL). The investigators evaluated the records of over 3.5 million people, including 936 with NHL, born between 1973 and 2008.
They reported that family history of NHL was associated with development of NHL in early life. Specifically, history of NHL in a sibling increased the risk of developing NHL roughly nine-fold while having a parent with NHL increased the risk of NHL roughly two-fold. Importantly, the overall incidence rate of NHL was 1.4 per 100,000 person-years (the number of people x the number of years of follow-up per person). Therefore, a two-fold increase, although statistically significant, would only have increased the rate to roughly 3 per 100,000 person years. Moreover, only 4 of the 936 cases had a sibling with NHL and 10 had a parent with NHL.
These small numbers, although statistically significant, make it difficult to make any definitive conclusions regarding the degree of risk. The lack of data regarding environmental exposures, infections, and other co-existing conditions (e.g., immunodeficiencies) make it difficult to determine whether the familial association of NHL is due to an inherited condition or some other unmeasured factor. Despite the issues, the results are consistent with the concept that genetic factors may contribute to NHL. It is possible that contemporary studies using next generation sequencing of the genomes of patients and family members could yield more conclusive results. The risks and benefits of such studies, however, need to be weighed very carefully.
By Peter Martin, MD
Cancer cells in mantle cell lymphoma (MCL) undergo uncontrolled proliferation due to overproduction of the protein Cyclin D1. The family of proteins called Cyclins combine with enzymes called Cyclin dependent kinases (Cdk) in a way that is analgous to gas in an engine. The Cdks are the engine but they rely on the Cyclins to make them work.
PD0332991 is an orally bioavailable (i.e., a pill) inhibitor of Cdk4/6, the Cdks that combine with Cyclin D1 in MCL. A recently published clinical trial performed at Weill Cornell Medical College and other sites around the United States demonstrated that PD0332991 could successfully stop MCL tumors from growing in several patients, including one response that lasted for more than 30 months. Biopsies taken from patients while receiving PD0332991 revealed that Cdk4/6 was effectively inhibited while a specialized kind of imaging, called FLT-PET, demonstrated that MCL cells had stopped proliferating. Although these results were promising, not every patient benefited, and the responses were not permanent.
Additional studies combining PD0332991 with other drugs based on promising laboratory data are currently underway at Weill Cornell. Click here for more information.