Autologous stem cell transplantation was associated with a significant survival benefit at 2 years, compared with induction therapy alone, in a subset of patients with high-risk non-Hodgkin’s lymphoma, based on results from a 40-site study conducted by the Southwest Oncology Group.
In the high-risk subgroup, the 2-year survival rate was 82% in the transplant group and 64% in the induction therapy only group (P = .01). The finding was not part of the preplanned analysis of the SWOG 9704 trial, however. The study was not powered to address the question, so the results must be cautiously interpreted, Dr. Patrick J. Stiff and his colleagues wrote in the study published Oct. 31 (N. Engl. J. Med .2013;369;1681-90).
"The finding needs to be verified prospectively, although undertaking such a trial would be difficult, given the small fraction of patients presenting with high-risk disease," wrote Dr. Stiff of Loyola University, Maywood, Ill., and his coauthors. "However, our analysis ... compares favorably to the 50% progression-free survival rate seen after treatment with (induction therapy) alone, suggesting that early transplantation may be warranted in high-risk disease."
Dr. Patrick Stiff
In the overall results of the study, however, patients with aggressive non-Hodgkin’s lymphoma experienced short-term benefits from autologous stem cell transplantation, but their long-term survival was similar to that of patients who had additional cycles of induction therapy.
By the median follow-up of 6 years, the estimated overall survival rate for the two groups was not statistically different at 74% and 71%, respectively. The multivariate analysis found a nonsignificant 26% increase in the risk of death in the control group (P = .30).
The researchers noted that 29% of the control patients who had a relapse or progression after standard therapy had long-term progression-free survival after salvage therapy that often included transplantation. "Thus, early transplantation and late transplantation achieve roughly equivalent overall survival in the combined risk groups," the researchers said.
In the SWOG 9704 study, 253 induction-eligible patients were randomly assigned to the transplantation group or the control group. Patients were a median of 51 years old at baseline. Most (89%) had B-cell lymphoma; the others had T-cell disease. The majority (63%) had stage IV disease; 31% had stage III disease, and 6% were stage II with bulky disease.
All had responded to five cycles of induction therapy with cyclophosphamide, doxorubicin, vincristine and prednisone with or without rituximab (CHOP and R-CHOP).
The 128 patients in the control group received three more CHOP cycles. The 125 patients in the transplantation group got one more CHOP cycle plus an autologous stem cell transplant.
The primary endpoints were 2-year progression-free and overall survival, with 6-year survival as a secondary endpoint.
Disease progression or death occurred at 2 years in 46 of the 125 patients in the transplantation group and in 68 of the 128 patients in the control group. In a multivariate analysis, the hazard ratio for progression or death in the control group vs. the transplantation group was 1.72 (95% confidence interval [CI], 1.18-2.51; P = 0.005; P = .002 in a one-sided test).
At a median follow-up of 6.3 years, however, 37 of the 125 patients in the transplantation group and 47 of the 128 patients in the control group had died. In a multivariate analysis, the hazard ratio for death in the control group versus the transplantation group was 1.26 (95% CI, 0.82-1.94; P = .30; P = .15 in a one-sided test).
The treatment effect did differ, however, between high risk patients and high-intermediate-risk patients for both progression-free survival (P = .04 for interaction) and overall survival (P = .01 for interaction).
In the subset of 165 high-intermediate risk patients, the 2-year progression-free survival rate was 66% among patients in the transplantation group and 63% among patients in the control group (P =.32). In the subset of 88 high-risk patients, the 2-year progression-free survival rates were 75% and 41%, respectively (P = 0001). The estimated overall survival rates for high-intermediate-risk patients in the transplantation and control groups were 70% and 75%, respectively (P = .48), and those for high-risk patients were 82% and 64% (P = .01).
Treatment-related adverse effects were more common in the transplantation group than the control group. The most common adverse events included infection (50% vs. 13%), gastrointestinal effects (26% vs. 5%), metabolic effects (13% vs. 1%), lung effects (11% vs. 2%), and cardiovascular effects (10% vs. 4%).
Six patients in the transplantation group died from treatment toxicity (lung hemorrhage in three; renal failure in one; infection in one; multiorgan failure in one). In the control group, there were three deaths (cardiovascular toxic effects, infection, and unknown factors.)