MabThera standard of care in DLBCL
Almost half (47%) of the patients who received 8 cycles of MabThera plus CHOP for DLBCL were probably cured compared with less than one-third with CHOP alone |
In 2000, the phase III GELALNH 98.5 trial1 comparing MabThera plus CHOP with CHOP alone was the first trial to demonstrate a significant benefit in terms of complete response (CR) rate, event-free survival (EFS) and, most importantly, overall survival compared with CHOP chemotherapy alone. Eight cycles of MabThera plus CHOP was subsequently approved for first-line treatment of DLBCL.
The GELA-LNH 98.5 trial randomised patients aged between 60 and 80 years with previously untreated DLBCL to CHOP plus MabThera or standard CHOP (375mg/m2 on day 1 of each of 8 cycles of CHOP chemotherapy).1 Of the 399 patients (median age 69 years) enrolled in this trial, a substantial proportion had high-risk disease, with 60% having age-adjusted International Prognostic Index (aaIPI) scores ≥2 and 65% having elevated lactate dehydrogenase levels.
A statistically significant benefit, with respect to the primary end point, EFS, as well as OS and CR, was observed with the addition of MabThera to CHOP at the time of the first pre-planned interim analysis after 12 months' follow-up.1 In the first complete analysis, at 2-year follow-up,1 the 2-year EFS was 57% for MabThera plus CHOP compared with 38% for CHOP alone (p<0.001) and corresponding 2-year OS was 70% and 57% (p=0.007). The benefits of MabThera plus CHOP over CHOP alone were maintained at median follow-ups of 5 years (p=0.01)2 and 7 years (p=0.0004).3
Thus, almost half (47%) of the patients who received 8 cycles of MabThera plus CHOP for DLBCL were probably cured compared with less than one-third (29%) with CHOP alone. Comparison of these data with the 2-year data reveal there were few relapses between 2 and 5 years, the majority occurring within the first 2 years of follow-up. Five-year OS was 58% in patients who received MabThera plus CHOP and 45% in those who received CHOP alone (p=0.0073).2
When patients were stratified according to the International Prognostic Index (IPI), MabThera plus CHOP significantly improved EFS compared with CHOP in low-risk as well as high-risk patients.2 Further subgroup analyses demonstrated that MabThera plus CHOP conferred significant benefits over CHOP alone irrespective of age or co-morbidity.
Safety data from 398 patients in the GELA-LNH 98.5 trial showed that MabThera did not add any clinically significant toxicity to CHOP chemotherapy.1 Overall, grade 3 and 4 adverse events (AEs) (which were taken to include grade 2 infections) occurred with similar frequency in the two arms (78.7% with MabThera plus CHOP, 74.0% with CHOP). Grade 1 and 2 AEs were more frequent in the MabThera plus CHOP arm, which most likely reflects the mild infusion-related reactions seen in previous studies of MabThera monotherapy. Grade 3 and 4 infusion-related reactions occurred in ~9% of patients during the first cycle of MabThera plus CHOP but the incidence decreased to <1% during the eighth cycle.
No long-term toxicity was associated with the MabThera plus CHOP combination after 5 years' median follow-up in the GELA-LNH trial, although there was a trend towards increased occurrence of infection in all MabThera plus CHOP patients after the end of treatment (12 vs 6 patients).2
The 7-year follow-up of the GELA-LNH trial also demonstrated that EFS and OS were significantly superior in patients treated with MabThera plus CHOP compared with CHOP alone.4 The 7-year EFS was 42% in the MabThera arm versus 25% for CHOP alone (p<0.0001) and OS at 7 years was 53% versus 36%, respectively (p<0.0004). The benefit in survival was seen in both low risk patients (aaIPI 0-1; 71% vs 49%, p=0.003) and high risk patients (aaIPI 2-3; 42% vs 28%, p=0.0213). This confirms the long-term benefit seen with the combination of MabThera and CHOP and highlights that patients should be treated similarly regardless of age or risk category. These findings are supported by those of the MinT study, which showed that MabThera plus chemotherapy significantly improves 3-year EFS (79% vs 59%, p<0.01) and OS rates (93% vs 84%, p<0.01) in younger DLBCL patients.5
References
1. Coiffier B, Lepage E, Briere J, et al. N Engl J Med 2002;346:235–242.
2. Feugier P, Van Hoof A, Sebban C, et al. J Clin Oncol; 2005;23:4117–4126.
3. Coiffier et al, Haematologica 2007;92(Suppl. 2) (Abstract 407).
4. Coiffier B, Feugier P, Mounier N, et al. J Clin Oncol 2007;25(Suppl. 16 Pt I) :443s (Abstract 8009).
5. Pfreundschuh M, Trümper L, Osterborg A, et al. Lancet Oncol 2006;7:379–391.
