A New Study Evaluates Early Autologous Stem Cell Transplantation for Aggressive Non-Hodgkin's Lymphoma

  • Date: 06 Nov 2013
  • Author: Remissions last longer, but survival not affected, except in highest risk patients
  • Topic: Haematologic malignancies

Performing early stem cell transplantation in patients with aggressive non-Hodgkin's lymphoma does not improve overall survival in high-risk patients, according to a study published on 31 October, 2013 in the New England Journal of Medicine. But early transplantation does appear to be beneficial among a small group of patients who are at the very high risk, the study found. Lead author is Dr Patrick Stiff, director of Loyola University Medical Center's Cardinal Bernardin Cancer Center. The study was developed by the SWOG cancer research cooperative group and funded by the USA National Cancer Institute. Dr Stiff is chair of the SWOG Bone Marrow and Stem Cell Transplantation Committee.

In the background for the current study, the authors explained that the efficacy of autologous stem cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index is controversial and untested in the rituximab era. The treatment with rituximab and CHOP regimen (R-CHOP) typically puts patients into remission. But many patients relapse and go on to get an autologous stem cell transplant after second-line chemotherapy.

The primary efficacy end points were 2-year progression-free survival and overall survival. The clinical trial included 40 sites in the United States and Canada. In addition to SWOG, the study included the Eastern Cooperative Oncology Group, Cancer and Leukemia Group B and Canadian NCIC Clinical Trials Group.

The study included 397 patients who were in defined groups of high risk or intermediate-high risk of relapsing. After initial chemotherapy, those who responded were randomly assigned to receive an autologous stem cell transplant (125 patients) or to a control group of 128 patients who received three additional cycles of the R-CHOP regimen. Enrolment began in 1999 and ended in 2007 (some of the patients in the beginning of the study did not receive rituximab).

After two years, 69% of the transplantation patients had no disease progression, compared with 55% of the control group (p = 0.005). However, the difference in two-year survival rates (74% in the transplantation group and 71% in the control group) was not statistically significant. This is probably because patients in the control group who relapsed were later offered salvage stem cell transplantation, the authors wrote.

Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (p = 0.04 for interaction) and overall survival (p = 0.01 for interaction).

While stem cell transplants did not improve overall survival among the entire group of high-risk and high-intermediate risk patients, the subset of high risk patients did appear to receive both a remission and survival benefit. A retrospective analysis of the data showed that among these high-risk patients, the two-year survival rate was 82% in the transplantation group and 64% in the control group.

"Early transplantation and late transplantation achieve roughly equivalent overall survival in the combined risk groups," researchers concluded, yet "early transplantation appears to be beneficial for the small group of patients presenting with high-risk disease."

According to Dr Stiff, this finding "hopefully will trigger discussions between such patients and their physicians as to the feasibility of doing early transplants."

Previous studies have found that patients who undergo stem cell transplants have a slightly higher risk of developing secondary cancers caused by the chemotherapy and/or radiation. However, the new study did not find a statistically significant difference – 11 patients in the control group developed secondary cancer, compared with 12 patients in the transplantation group.

The authors concluded that early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation. The researchers are continuing to analyze the data and such additional analysis may help fine-tune the results.

The study was supported in part by Public Health Service Cooperative Agreement grants from the USA National Cancer Institute, Department of Health and Human Services, by grants from the Canadian Cancer Society Research Institute and in part by Bristol-Myers Squibb.

The SWOG-9704 ClinicalTrials.gov number is NCT00004031.

Reference:

Stiff P, Unger J, Cook J,et al. Autologous Transplantation as Consolidation for Aggressive Non-Hodgkin's Lymphoma. N Engl J Med 2013; 369:1681-1690.

Dr Porcu reports receiving consulting fees from Hospira and Medicis, lecture fees from Physician Education Resources, honoraria from Easton Associates, ClearView Health Care Partners, and E Squared Communications, and grant support through his institution from Millennium. Dr Kahl reports receiving payment for board membership from Roche, Seattle Genetics, Millennium, and Cell Therapeutics and consulting fees from Genentech and Celgene. Dr Miller reports receiving grant support through his institution from Spectrum, Celgene, and Abbott. Dr Tubbs reports receiving lecture fees from Ventana Medical Systems and grant support through his institution from Ventana Medical Systems and Abbott Molecular Vysis. Dr Friedberg reports receiving consulting fees from Genentech, Lilly, and Trubion. Dr LeBlanc reports holding a pending patent regarding the uses of diffuse large-B-cell lymphoma markers. Dr Rimsza reports receiving lecture fees from Ventana Medical Systems, and grant support through her institution from Ventana Medical Systems, Spectrum Pharmaceuticals, and Merck. Dr Fisher reports receiving consulting fees from Micromet, Bio Linx, Boehringer Ingelheim, Roche, and Pfizer. No other potential conflict of interest relevant to this article was reported.