Early results of a randomized phase III GITMO/FIL study comparing CHOP-R vs. R-HDS + ASCT as primary treatment in 134 FL pts, aged less than or equal to 60 yrs with aaIPI greater than 1/IIL score greater than 2, have shown superior disease control with R-HDS but no overall survival advantage ( Ladetto et al, Blood 2008 ).
Researches have presented an updated analysis from July 2013 at a median follow-up of 9.5 years including 125 patients of 134 originally randomized patients ( 61 CHOP-R/64 of R-HDS ).
Median age was 51 years, M/F ratio 74/51, aaIPI 2-3 90%, retrospective FLIPI greater than 2 60%, high LDH 49%, bulky disease 62%, B-symptoms 45%, BM+ 86%.
Analysis was intention to treat and event-free survival the primary endpoint. Minimal residual disease was done by nested and RQ-PCR.
Complete response ( CR ) rate was 70.4% ( 57% with CHOP-R and 83% with R-HDS, p
At median follow-up, 88 patients ( 70.4% ) are alive. 19 patients died of lymphoma ( CHOP-R:11; R-HDS: 8 ), 9 of second cancer ( CHOP-R: 3; R-HDS: 6 ) and 9 for other causes, including 4 early toxic deaths.
Overall survival is 78% and 70% at 5 and 10 yrs, respectively. There was no difference in overall survival, with 5 and 10 years projections respectively of 75% and 70% for CHOP-R and 81% and 70% for R-HDS ( p=0.96 ).
Response to primary treatment had a major impact on overall survival, with 5 and 10 year survival projections respectively of 90% and 80% for patients achieving complete response, and of 49 and 43 for those with less than complete response ( p less than 0.001 ).
Similarly, molecular remission achievement was associated with prolonged overall survival, with 5 and 10 year survival projections respectively of 89% and 83% for patients achieving molecular remission vs 76% and 57% for those remaining PCR-positive ( p = 0.03 ).
In conclusion, the results have indicated that: i) 70% of high-risk follicular lymphoma now experiences a prolonged survival, being alive at 10 years; ii) the superior disease control of R-HDS does not translate in any overall survival advantage, iii) achieving complete response and molecular remission is crucial for long-term overall survival; iv) progression remains the major cause of death, though a major toll is paid to secondary neoplasms, particularly acute myeloid leukemia ( AML ). ( Xagena )
Tarella C et al, J Clin Oncol 32:5s, 2014 (suppl; abstr 8531) - 2014 ASCO Annual Meeting