Several important studies were presented at the ASCO lymphoma oral session.
In the first presentation, G. Salles from France presented the long-awaited data from the Primary Rituximab and Maintenance (PRIMA) study in newly diagnosed patients with advanced stage follicular lymphoma (FL) requiring therapy. This GELA-sponsored international Phase III study investigated two years of rituximab (R) maintenance in FL patients responding to first-line immuno-chemotherapy consisting of either eight cycles of R-CVP, or six cycles of R-CHOP or R-FCM (plus two additional rituximab infusions). The study was initiated in 2004 and enrolled 1,217 patients from 25 countries at 223 centers. It completed enrollment in April 2007.
There were 1,207 evaluable patients treated with RCHOP (n=885), RCVP (n=272) or RFCM (n=45), and 1,018 responding patients were randomized to either rituximab or observation (513 observation, 505 rituximab maintenance). Median follow-up was 25 months from randomization (31 months from study entry).
There was a significant (stratified log-rank, P<.0001) improvement in the primary endpoint PFS, for R-maintenance (hazard ratio [HR]=0.50; 95% CI [0.39-0.64]; two-year PFS 82%; 95% CI [78-86%] vs. 66% [61-70%] for observation). An independent response review committee confirmed the significant improvement in PFS in the R-maintenance arm (HR=0.53 [0.41-0.68]). Time to next anti-lymphoma treatment, as well as response rate at the end of maintenance or observation, were significantly improved in the R-maintenance arm. Remarkably, the benefit of rituximab maintenance was observed in all subgroups, regardless of type of induction therapy, age, FLIPI score, or quality of response (CR vs PR).
The authors concluded that the PRIMA study provided evidence for a new standard of care for FL patients in need of treatment.
More promising news
In a different study, R. Pettengell examined the role or rituximab for in vivo purging and as maintenance after autologous stem cell transplant (ASCT). From October 1999 to April 2006, 280 of a planned 420 patients with rFL in first (n=16), second (n= 222) or third remission (n=41) who achieved either a complete remission (n=83) or a very good partial remission (n=196) to induction chemotherapy, with limited bone marrow infiltration (<25% B-lymphocytes), underwent a single randomization in a 2x2 design to RP and RM, n = 69; RP, n = 72; RM, n = 69; No R n = 70.
PFS at five years was 54.3% versus 47.8% for in vivo purging versus none (logrank PFS; p=0.20; HR 1.23, 95%CI: 0.89 - 1.72). PFS at five years was 58.8% versus 42.6% in patients receiving R maintenance versus none (logrank PFS; p=0.02; HR 1.50, 95%CI: 1.07 - 2.09). PFS at five years was 54.8% versus 37.6% in patients receiving R purging and maintenance versus none (logrank PFS; p=0.05; HR 1.44, 95%CI: 1.004 - 2.05). The success of salvage therapy is reflected in an overall survival at five years of 80.8% (95% CI: 75.5 - 85.0). Conclusions: This study shows that peri-autograft, R in vivo purging and two years maintenance post-autograft gives a superior PFS compared to no rituximab.
Collectively these data demonstrate:
• Rituximab maintenance after induction with R-chemo in patients with advanced stage FL improved PFS
• Rituximab maintenance after ASCT in rituximab-naive FL patients in second or third remission also improves PFS
However, it's important to keep in mind that:
• This data is applicable for patients with FL. Previous randomized study failed to show benefit for rituximab maintenance after induction with RCHOP in patients with newly diagnosed diffuse large cell lymphoma
• We still do not know if giving rituximab maintenance for longer than two years would produce better outcomes or more toxic effects. So for now, if one wants to use rituximab maintenance, one should give it for two years, unless on clinical trials.