Frontline High-Dose Chemo Fails to Improve High-Risk DLBCL Outcomes


Frontline intensive therapy with rituximab plus high-dose sequential chemotherapy did not improve outcomes for high-risk patients with DLBCL compared with treatment with R-CHOP-14.

Frontline intensive therapy with rituximab plus high-dose sequential chemotherapy (R-HDS) did not improve outcomes for high-risk patients with diffuse large B-cell lymphoma (DLBCL) compared with treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14, according to the results of a study published in the Journal of Clinical Oncology.

Prior to the approval of rituximab, high-dose chemotherapy programs followed by transplant were proposed as a treatment method for high-risk patients with DLBCL; however, trials evaluating this method have had conflicting results. A phase II trial of R-HDS showed that the regimen was feasible and active in this patient population.

In this phase III study, Sergio Cortelazzo, of Ospedale Centrale di Bolzano, Bolzano, and colleagues randomly assigned 246 high-risk patients with high-intermediate or high International Prognostic Index scores to R-CHOP or R-HDS; 235 patients were included in the intent-to-treat analysis. The primary efficacy endpoint was 3-year event-free survival.

“Our results indicate that CHOP chemotherapy, optimally supplemented by eight doses of rituximab, remains the standard of care also for this group of patients at higher risk for disease resistance or recurrence,” the researchers wrote.

No difference was found between R-CHOP and R-HDS regimens for:

• Complete response (78% vs 76%)
• Partial response (5% vs 9%)
• No response (15% vs 11%)
• Early treatment mortality (2% vs 3%)

Similarly, after a median of 5 years follow-up, the 3-year event-free survival was 62% for patients assigned R-CHOP compared with 65% for patients assigned R-HDS. At 3 years follow-up, patients assigned to R-HDS had significantly improved disease-free survival (91% vs 79%; P = .034), but the researchers noted that this advantage disappeared because of late-occurring treatment-related deaths.

Treatment was discontinued in 19% of patients assigned to R-HDS compared with 5% assigned R-CHOP (P < .001). Patients assigned to R-HDS had significantly higher hematologic toxicity (P < .001) and more infectious complications (P < .001) compared with R-CHOP.

Finally, there was no difference between the two treatment arms for progression-free or overall survival.

“Interestingly, the subgroup analysis describing the outcome of patients who did not discontinue the allocated treatment because of medical or patient decision or toxicity showed a significant benefit of the R-HDS program in terms of progression-free survival and disease-free survival, but not overall survival,” the researchers wrote.

Based on these results, the researchers concluded that these two regimens are equally effective for these high-risk patients.

“Whether the addition of new drugs, such as lenalidomide and ibrutinib or monoclonal antibodies such as obinutuzumab, to R-CHOP therapy will be able to improve the outcome of high-risk patients with DLBCL is still under investigation,” the researchers wrote.

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