The natural history of follicular lymphoma has not changed over the last 30 years (

Horning, S.J., Seminars in Oncology 20: 1993, 75–88
). Median survivals have ranged from 7 – 10 years and the disease is generally considered incurable as there has been no plateau in the survival curve. However, multiple new treatment options, including biologic agents, have been developed in the last decade and their impact on the natural history of follicular lymphoma remains unknown. In order to determine the cumulative effects of all these new treatment options, we identified all previously untreated, advanced stage, follicular lymphoma patients treated with three sequential treatment approaches: CHOP chemotherapy +/− nonspecific immunostimulants (SWOG 7426 and 7713: 1974 – 1978), ProMACE-MOPP +/− interferon (SWOG 8809: 1988 – 1994), and CHOP followed by monoclonal antibody therapy (SWOG 9800 and 9911: 1998 – 2000) and determined their Progression-Free Survival (PFS) and Overall Survival (OS). More specificially, the monoclonal antibody trials included CHOP followed by rituximab (SWOG 9800) and CHOP followed by 131I-Tositumomab (SWOG 9911). The PFS are shown below:

Progression-Free Survival by Treatment Strategy

TREATMENTNDEATH/PROGRESSION4-YR PFS
CHOP + MoAb 179 75 61% 
ProMACE 425 290 48% 
CHOP 356 257 46% 
TREATMENTNDEATH/PROGRESSION4-YR PFS
CHOP + MoAb 179 75 61% 
ProMACE 425 290 48% 
CHOP 356 257 46% 
View Large

The results demonstrate that the PFS remained unchanged until the recent studies that utilized CHOP followed by a monoclonal antibody for initial treatment. The results of OS from these three groups are shown below.

Overall Survival by Treatment Strategy

TREATMENTNDEATH4-YR OS
CHOP + MoAb 179 18 91% 
ProMACE 425 189 79% 
CHOP 356 226 69% 
TREATMENTNDEATH4-YR OS
CHOP + MoAb 179 18 91% 
ProMACE 425 189 79% 
CHOP 356 226 69% 
View Large

In contrast to the PFS, OS has increased with each subsequent study.

These data are consistent with the hypotheses that initial therapy with chemotherapy followed by a monoclonal antibody has a significant impact on PFS (p= .005) and OS (p < .0001) and that, even in earlier studies where we could not demonstrate improved initial treatment, sequential new treatment options have also changed the OS (p < .0001) and thus the natural history of follicular lymphoma.

Topics:
follicular lymphoma, cyclophosphamide, doxorubicin, prednisone, and vincristine, monoclonal antibodies, chemotherapy regimen, biological products, human leukocyte interferon, immunologic adjuvants, interferons, mopp protocol, rituximab

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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