Limited stage DLBCL: continued risk of relapse shown to be independent of treatment modality in the SWOG S8736 study

This article was written by Dr Deborah M Stephens from the University of Utah, U.S.A. along with her colleagues from various research institutes and corresponding author Dr Sonali M Smith, Section of Hematology/Oncology, University of Chicago, U.S.A; this was published in the Journal of Clinical Oncology on September 1st. The article highlights clinical outcomes such as Progression Free Survival (PFS) and Overall Survival (OS) that were obtained from a long term analysis of the Southwest Oncology Group (SWOG) S8736 study randomizing CHOP8 versus CHOP3RT; and evaluated alongside data from another study (SWOG S0014, NCT00005089) wherein limited-stage DLBCL patients received R-CHOP3RT.

The key points from the study are as follows:

• In the S0014 study, patients were found to have a higher-risk disease (by design), because in these patients a stage-modified score of 0 were excluded. In contrast, approximately 30% of S8736 patients had a stage-modified score of 0
• With a median follow-up of 17.7 years, median PFS was 12.0 (95% CI, 8.8 to 14.3) for limited-stage DLBCL patients treated with CHOP8 and 11.1 years (95% CI, 8.9 to 14.4) for the same patients population treated with CHOP3RT. There were no statistically significant differences in PFS between the two groups
• Median OS was 13.0 (95% CI, 10.4 to 15.2) and 13.7 years (95% CI, 11.1 to 19.4) for patients who received CHOP8 and CHOP3RT, respectively. No statistically significant differences were found in OS between the groups
• Median PFS and OS were not reached in patients in the S0014 study receiving rituximab and CHOP3RT (the median follow-up was 12 years)
• The most common cause of death in patients (n=33 CHOP8; n=30 CHOP3RT arms) was due to relapse of DLBCL
• In the CHOP8 cohort, 5- and 10-year cumulative incidence of progressive disease (PD) were 23 and 28% respectively. In the CHOP3RT cohort, 5- and 10-year cumulative incidence of PD were 18% and 29% respectively. No significant differences were found in cumulative incidence of PD between the groups

Conclusions

Extended survival data with more than 17 years of follow-up showed similar outcomes, continuous treatment failures and absence of a PFS plateau in the CHOP3RT versus CHOP8 arms of the S8736 study. It was interesting to note even with 12 years of follow-up, addition of rituximab (S0014 study) to combined-modality therapy did not moderate the risk of continued late relapse in patients, largely due to the unique biology of limited-stage DLBCL.

The complete article can be found here.

Continued Risk of Relapse Independent of Treatment Modality in Limited-Stage Diffuse Large B-Cell Lymphoma: Final and Long-Term Analysis of Southwest Oncology Group Study S8736

Abstract

Purpose

Utility of combined-modality therapy for patients with limited-stage diffuse large B-cell lymphoma (DLBCL) was shown in the Southwest Oncology Group (SWOG) S8736 study, where three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus radiotherapy (CHOP3RT) improved 5-year progression-free (PFS) and overall survival (OS) compared with eight cycles of CHOP (CHOP8). Subsequent analysis showed an unexpected overlap of the PFS curves. We aimed to confirm and investigate this observation by performing long-term analysis of SWOG S8736 and evaluating these data alongside data from similar patients receiving rituximab and CHOP3RT (SWOG S0014 study).

Patients and Methods

A subset of patients with limited-stage DLBCL randomly assigned to CHOP8 (n = 150) or CHOP3RT (n = 158) in S8736 was analyzed along with a 56-patient subset treated in S0014 for long-term PFS and OS.

Results

Median follow-up in S8736 was 17.7 years. In patients receiving CHOP8 and CHOP3RT, median PFS was 12.0 (95% CI, 8.8 to 14.3) and 11.1 years (95% CI, 8.9 to 14.4), respectively. There were no statistically significant differences in PFS between the groups (P = .73). Median OS was 13.0 (95% CI, 10.4 to 15.2) and 13.7 years (95% CI, 11.1 to 19.4) for patients treated with CHOP8 and CHOP3RT, respectively. Similarly, there were no statistically significant differences in OS between the groups (P = .38). With a median follow-up time 12 years in S0014, 5- and 10-year OS were 82% and 67%, respectively, with a persistent pattern of relapse despite the addition of rituximab.

Conclusion

Although 5-year PFS and OS were improved after early analysis in patients with limited-stage DLBCL receiving CHOP3RT versus CHOP8, extended survival data showed similar PFS and OS, with continuous treatment failure. The addition of rituximab (S0014) to combined-modality therapy did not mitigate the continued relapse risk, underscoring the value of prolonged clinical trial patient observation and possible unique biology of limited-stage DLBCL.