Maurie Markman, MD
Editor-in-Chief of OncologyLive
Senior vice president for Clinical Affairs and National Director for Medical Oncology
Cancer Treatment Centers of America, Eastern Regional Medical Center
With more than 4200 abstracts, the American Society of Hematology’s 2011 annual meeting was filled with a tremendous quantity of highly provocative and paradigm-changing new information regarding the management, epidemiology, and basic biology of hematologic conditions, including malignant disease. While it is impossible to attempt in a short article to review the contents and impact of this large international meeting, this commentary will focus on several very interesting presentations that will surely stimulate highly clinically relevant discussion regarding disease management within the realm of the hematologic malignancies.
Risk of Second Cancers in MM Therapy Examined
It is well recognized that multiple myeloma (MM) itself and the therapy employed in the management of this cancer have the potential to be associated with second malignancies. In an effort to determine the magnitude of this risk, and any changes in such risk that may have resulted from the introduction during the past decade of increasingly effective antineoplastic strategies to treat the condition, investigators examined patients with MM contained within the large Surveillance, Epidemiology, and End Results database from the years 1973 to 2008.1
Specifically explored was the relationship between the risks of developing a second cancer after a diagnosis of MM during particular time periods that corresponded to the introduction of novel therapeutic strategies (eg, thalidomide, bortezomib, lenalidomide). The primary endpoint in the analysis was the documentation of a second malignancy at least 2 years after the diagnosis of MM. The only secondary cancers excluded from this evaluation were in situ malignancies (other than bladder and breast) and myelodysplastic syndrome.
The analysis, which included more than 29,000 patients, found an association between the risk of secondary malignancies and older age, male sex, and previous radiation or surgery. The researchers also found a greater risk of a second cancer during the most recent time periods analyzed.
Although this report raises the question of the immunosuppressive effects of the recently introduced potent novel therapeutics and the potential risk of the development of an additional cancer, it is important to note that with more effective treatment, patients also live longer and are therefore at greater risk (due to length of survival) to experience such an unfortunate event. Further research into this question is clearly indicated and the long-term consequences of newer therapeutic agents need to be carefully monitored.
Rituximab antibodies (turquoise) bind to the CD20 cell-surface markers on B-cells.
Image courtesy of Roche
Maintenance Rituximab in Follicular Lymphoma Questioned
A second paper reported the results of a most interesting phase III randomized trial that the Eastern Cooperative Oncology Group conducted to examine the potential clinical utility of a maintenance approach employing rituximab to prevent subsequent disease progression in patients with low tumor burden follicular lymphoma.2
The hypothesis supporting the conduct of this trial was that the administration of rituximab (on an every 3-mo schedule) following an initial response to the agent in this specific clinical setting might substantially delay the time to subsequent disease progression.
However, the trial failed to demonstrate a clinically meaningful benefit associated with the maintenance approach. In fact, at 3-year follow-up, while 95% of the patient population randomized to receive maintenance rituximab remained without the requirement for cytotoxic therapy, 86% of patients who did not receive maintenance remained in a similar state. And although this difference was statistically significant (P
= .027), there was no observable difference in the health status of the patient populations or their overall quality of life. Further, the amount of treatment received by the maintenance group (and the cost of this therapy) was substantially greater than in the population observed until evidence of disease progression.