S. Cortelazzo presented with his Italian colleagues the results of a randomized open-label, multicenter phase III trial performed in 246 high-risk DLBCL with high-intermediate (56%) or high IPI score who received either R-CHOP14 during 8 cycles or R-HDS (high-sequential chemotherapy) with autologous stem cell transplantation. They published their results in J Clin Oncol in October 2016.
Their key findings are:
- No significant difference in CR or CRu rates between the 2 arms (78% R-CHOP, 76% R-HDS, p=0.74)
- No significant difference in ORR: 83% vs 85% (p=0.65)
- 3-year EFS: no difference between R-CHOP (62%) and R-HDS (65%), p=0.83
- 3-year DFS: R-CHOP, 79% vs 91% (R-HDS), p =0.033, but late relapses in the R-HDS group leading to a non-significant difference in DFS between the 2 regimens at 7 years.
- No difference in OS (74% vs 77%, p=0.64)
- Significantly lower hematological toxicity (neutropenia, anemia, thrombocytopenia), lower frequency of severe infections, lower number of AEs including the serious AEs, fewer episodes of GI toxicity in the R-CHOP arm
In conclusion, in high-risk DLBCL, R-HDS followed by ASCT and R-CHOP14 were equally effective.
Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas
Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT.
Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis.
Results Clinical response (complete response, 78% v 76%; partial response, 5% v9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2%v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% (P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74%v 77%, respectively; P = .64). Significantly higher hematologic toxicity (P < .001) and more infectious complications (P < .001) were observed in the R-HDS arm.
Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.