Early autologous stem cell transplantation may improve progression-free survival (PFS) among patients with International Prognostic Index high-risk or high-intermediate–risk non-Hodgkin lymphoma (NHL) after a response to induction therapy; however, it does not appear to improve overall survival (OS), according to a new study by Chicago researchers.1
“The question is timing,” said lead study investigator Patrick Stiff, MD, Director of Loyola University Medical Center’s Cardinal Bernardin Cancer Center in Chicago, IL. “This is the first study to report this.”
Although performing early stem cell transplants in patients with aggressive NHL was not shown to improve OS in high-risk patients, Dr. Stiff said early transplantation did appear to be beneficial among a small group of patients who were at highest risk. According to Dr. Stiff, the efficacy of stem cell transplantation following the first remission remains controversial and was untested in the rituximab era in patients with diffuse, aggressive NHL who are categorized as high-intermediate risk or high-risk until now.
The study, which included 370 patients from the United States and Canada, was designed to determine whether undergoing an early stem cell transplant (without waiting to see whether a patient relapses) would increase survival. After initial successful chemotherapy, patients were randomly assigned to receive either an autologous stem cell transplant (n = 125) or to a control group (n = 128) that received three additional cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP alone. Enrollment began in 1999 and ended in 2007. In the beginning of the study, some of the patients did not receive rituximab.1
After 2 years, 69% of the patients who received a transplant had no disease progression compared with 55% of the control group. However, the difference in 2-year survival rates—74% in the transplantation group versus 71% in the control group—was not statistically significant. Among the highest-risk patients, the 2-year survival rate was 82% in the transplantation group and 64% in the control group in a retrospective analysis.
Dr. Stiff said that early transplantation and late transplantation achieve roughly equivalent OS in the combined risk groups, yet early transplantation appears to be beneficial for the small group of patients presenting with high-risk disease.
Previous studies have found that patients who undergo stem cell transplants have a slightly higher risk of developing secondary cancers; however, this study did not find a statistically significant difference between the two arms. Lymphoma expert Nina Wagner-Johnston, MD, a medical oncologist at Washington University School of Medicine in St. Louis, MO, said that the current study confirms the findings of prior phase 2 studies and suggests that intensification with an autologous stem cell transplant in first remission for patients does not provide an OS benefit.
“This is largely due to the fact that many patients can be adequately salvaged at the time of relapse, as seen in this study where 29% of patients with relapsed disease in the control arm had long-term PFS following salvage therapy,” Dr. Wagner-Johnston told ChemotherapyAdvisor.com
Ajay Gopal, MD, director of clinical research at the Seattle Cancer Care Alliance in Seattle, WA, indicated the unplanned subset analysis of the highest-risk patients suggested a benefit in this small group. However, Dr. Gopal urges caution in routinely transplanting all of these patients, and noted that positron emission tomography (PET) findings also need to be considered. “The authors correctly point out the current and future of DLBCL [diffuse large B-cell lymphoma] treatment, namely, with improved risk stratification by means of FDG [fluorodeoxyglucose]-PET [positron emission tomography] imaging, may select the poor responders who are more likely to relapse,” Dr. Gopal told ChemotherapyAdvisor.com. “It is hoped that data from this study will help refine the ability to predict which patients should be transplanted as part of initial therapy and which ones are likely to be cured with R-CHOP alone.”
Olatoyoski Odenike, MD, associate professor of medicine at the University of Chicago School of Medicine in Chicago, IL, agreed. Dr. Odenike explained that the field is changing so rapidly that it is important to look at these findings in terms of current new imaging techniques. “PET scanning helps further refine risk today. Patients with positive PET after the initial induction chemotherapy phase are generally considered candidates for transplantation due to the poor prognosis associated with that situation,” said Dr. Odenike.
“Transplantation should not be part of routine therapy for patients after their initial therapy,” Dr. Stiff told ChemotherapyAdvisor.com. “I think oncologists should discuss these findings with their patients and let them know what the outcomes were so they can know what to expect,” he continued.
- Stiff PJ, Unger JM, Cook JR, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 2013;369(18):1681-1690.90