Long-term follow-up from two randomized trials shows that the treatment advantage initially seen by adding radiotherapy to the CHOP regimen in patients with limited-stage diffuse large B-cell lymphoma disappeared over time.
After a median follow-up of nearly 18 years, there were no significant differences in either progression-free survival (PFS) or overall survival between patients who had received standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) for 8 cycles (CHOP8), or 3 cycles of CHOP with involved-field radiotherapy (CHOP3RT), reported Deborah M. Stephens, DO, of the University of Utah in Salt Lake City, and her colleagues.
The addition of rituximab to CHOP plus involved-field radiotherapy (IFRT) in a separate cohort did not appear to reduce the continued relapse risk, the investigators noted (J Clin Oncol. 2016 Jul. doi: 10.1200/JCO.2015.65.4582).
The findings suggest that long-term follow-up of patients enrolled in clinical trials may provide clinically important additional information, and that limited-stage diffuse large B-cell lymphoma (DLBCL) may have a biology that is distinctly different from that of advanced stage DLBCL, the investigators wrote.
Initial results from the SWOG (Southwest Oncology Group) Study 8736, published after a median follow-up of 4.4 years, showed that CHOP3RT was associated with significantly better 5-year PFS and OS rates, compared with patients treated with CHOP8.
A second trial, SWOG Study 0014, looked at the addition of rituximab (Rituxan) to CHOP plus IFRT in patients with high-risk DLBCL with at least one adverse feature of the stage-modified International Prognostic Index. In this trial, after a median follow-up of 5.3 years, 4-year PFS was 88%, and 4-year OS was 92%.
5 years not enough
Results of both trials were published around the 5-year follow-up mark. However, an analysis of 10-year follow-up data from the S8736 trial, published only as an abstract (Blood. 98:724a-725a, 2001; abstr 3024), showed that “the survival curves for CHOP8 and CHOP3RT, surprisingly, began to overlap,” Dr. Stephens and her colleagues wrote.
“Additionally, for both S8736 and S0014, no plateau had been reached in the PFS curves. These data contrasted the expected cure rates for advanced-stage DLBCL, leading to the hypothesis that limited-stage DLBCL may have a unique biology from its advanced-stage counterpart,” they added.
Although more than half of patients with advanced-stage diffuse large B-cell lymphoma (DLBCL) can be cured with anthracycline-based chemotherapy, cure rates are markedly lower among patients with limited-stage disease, defined as Ann Arbor stage I or II, confined to a single irradiation field. Limited-stage disease accounts for approximately one-third DLBCL cases.
To see whether the trends observed at 10 years continued, the investigators conducted a survival analysis from S8736 and compared the data from similar patients in the S0014 study.
They found that after a median follow-up of 17.7 years in S8736, median PFS was 12.0 years for patients treated with CHOP8, and 11.1 years for patients treated with CHOP3RT, a difference that was not statistically significant.
Median OS was 13.0 and 13.7 years, respectively, and was also not significant.
In S0014, after a median follow-up of 12 years, the 5-year OS rate was 82%, and 10-year rate was 67%. In this trial, the investigators observed “a persistent pattern of relapse despite the addition of rituximab.”
“The populations were not entirely identical; however, even the addition of rituximab as per S0014 to combined-modality therapy did not seem to mitigate the continued relapse risk, underscoring the value of prolonged observation of clinical trial patients and possible unique biology of limited-stage DLBCL,” Dr. Stephens and her associates wrote.
The study was sponsored by grants from the National Institutes of Health. Dr. Stephens reported having no financial disclosures. Several coauthors disclosed research funding, consulting, speakers’ bureau participation or travel expenses from various oncology drug makers.