High-Risk NHL Patients Benefit From Autologous Stem Cell Transplant

An 8-year study in patients with intermediate- to high-risk non-Hodgkin lymphoma shows that an autologous transplant following induction chemotherapy improves survival in high-risk patients.

An 8-year study in patients with intermediate- to high-risk non-Hodgkin lymphoma (NHL) shows that an autologous transplant following induction chemotherapy improves survival in high-risk but not intermediate-risk patients. The results are published in the New England Journal of Medicine.

The standard of care for diffuse, aggressive NHL is a four-component chemotherapy regimen called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab.

The trial did not show an overall survival benefit when the entire patient dataset was analyzed although progression of aggressive NHL did slow significantly.

“High-risk patients with diffuse large B-cell lymphoma (DLBCL) as defined by the International Prognostic Index (IPI) may benefit from initial therapy with R-CHOP plus an autologous stem cell transplant rather than receiving R-CHOP initially and a transplant if and when they relapse,” said study author Richard I. Fisher, of the Fox Chase Cancer Center and Temple University School of Medicine in Philadelphia.

In the study, researchers randomized 253 patients 1:1 to either continue chemotherapy or to receive an additional round of induction chemotherapy followed by an autologous stem-cell transplantation. All patients had initially responded to induction therapy with CHOP or R-CHOP. Patients randomized to the transplant group also received total-body irradiation or high-dose chemotherapy prior to their transplant. The median age of patients in the trial was 51.

The 2-year progression free survival was 69% in the transplant group compared with 55% in the chemotherapy group (P = .005). At 2 years, 46 transplant patients had died compared with 68 control-group patients.

The 2-year overall survival rates were not much different: 74% and 71% in the experimental and control groups, respectively (P = .30). However, exploratory analysis showed a difference in both overall survival and progression-free survival when high-risk and intermediate-risk patients were compared. The 2-year overall survival rate was 82% in the transplant arm and 64% in the control arm (P = .01).

The minimal difference in improvement of overall survival is likely due to the patients in the control arm who received salvage transplantation following progression on chemotherapy treatment, said the authors.

The trial was started in 1999 before R-CHOP had become a standard treatment. Patients enrolled reflected the wide range of NHL subtypes.

Four deaths on the trial occurred during the initial 5-cycle chemotherapy induction phase. More grade 3 and 4 adverse events occurred among patients in the transplant group. Fifty percent of transplant patients had a grade 3/4 infection compared with 13% of the control-group patients. Other grade 3/4 adverse events that were more frequent in the experimental group included gastrointestinal, metabolic, lung, and cardiovascular events. A total of six patients in the transplant group died as a result of toxicities while on treatment compared with three patients in the control group.

“While it is certainly true that some elderly patients or those with comorbid conditions may not be able to undergo transplantation, this study shows that the majority of patients meeting the eligibility requirements of this trial were able to undergo successful autologous stem cell transplant with acceptable toxicity,” said Fisher.

Fisher says he and his colleagues are working on biomarker and genetic approaches to improve survival for the high-risk patient group that is most likely to benefit from upfront transplantation.

Writing an editorial on the results, Noel Milpied, MD, of the University Hospital and University in Bordeaux, Bordeaux, France, says the results are promising for high-risk patients but thinks the community needs to consider whether autologous transplants are a therapy approach that can be broadly applied to the clinic.

Currently, approximately 15% of NHL patients are at the highest risk for non-response to standard therapies. About 25% are at highest risk for relapse.

Milpied emphasizes the use of new molecular and imaging techniques including microarray analyses, immunohistochemistry, and positron emission tomographic scanning to parse patients into those who are likely to continue to respond to R-CHOP and those at high risk for relapse for whom a transplant should be considered.

Aggressive lymphoma is generally treated with R-CHOP. This works for patients with diffuse large B-cell lymphoma, but for high- and intermediate-risk patients, the success rate is only 50%. According to Dr. Milpied, three previous clinical trials did not show a benefit from upfront autologous stem cell transplantation but these trials were different from the one reported here. The previous studies tested transplant only in those patients with diffuse large B-cell lymphoma who were treated with rituximab.