ORLANDO – Rituximab that was added to the ACVBP regimen was associated with significantly improved overall survival, compared with rituximab added to the CHOP regimen, in patients younger than age 60 with diffuse, large B-cell lymphoma, based on results of a study presented at the annual meeting of the American Society of Hematology.
The 3-year overall survival rate was 92% among patients younger than age 60 years who had diffuse, large B-cell lymphoma (DLBCL) and were assigned to receive R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone). The 3-year overall survival rate was 84% for patients who were assigned to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The difference in survival was significant (R-ACVBP hazard ratio, 0.439; P = .0071), reported Dr. Christian Recher of the Centre Hôpitalier Universitaire (CHU) Purpan in Toulouse, France.
In addition, R-ACVBP was associated with significantly better 3-year event-free survival (81% vs. 67%; HR, 0.559; P = .0035), progression-free survival (87% vs. 73%; HR, 0.482; P = .0015), and disease-free survival among complete responders (91% vs. 80%; HR, 0.393; P = .0019).
"R-ACVBP should be the standard of care for younger patients with this disease," said Dr. Recher on behalf of colleagues in the GELA (Groupe d'Étude des Lymphomes de l'Adulte) LNH03-2B study.
Although R-CHOP has changed the prognosis of DLBCL for the better, many patients are refractory to initial therapy or may relapse after achieving a complete response, he said. One recent study suggests that patients who experience relapse or have refractory disease after R-CHOP have poor outcomes, with a 3-year event-free survival rate of 21% (J. Clin. Oncol. 2010;28;4184-90).
Critical questions in the care of these patients include the optimal rituximab dosage and schedule, and the optimal chemotherapy to match it with, Dr. Recher said.
The randomized, open-label trial compared R-CHOP with R-ACVBP in 380 patients aged 18-59 years (median age, 47 in the R-ACVBP arm and 48 in the R-CHOP arm), with an age-adjusted IPI (International Prognostic Index) score of 1.
Patients who were randomized to R-ACVBP received induction with four cycles delivered every 2 weeks, plus intrathecal methotrexate on day 2, with granulocyte colony-stimulating factor (G-CSF) support from day 6 to day 13 of each cycle. These patients then received sequential consolidation therapy consisting of two courses of methotrexate plus leucovorin rescue, followed by four courses of rituximab, etoposide, and ifosfamide on day 1 and two courses of cytosine-arabinoside for 4 days, with consolidation courses administered at 14-day intervals.
Patients who were randomized to R-CHOP received eight cycles for 21 days each, along with intrathecal methotrexate on day 1 of the first four cycles.
The primary end point was event-free survival. Secondary end points were response rate (evaluated according to the Cheson criteria of 1999), progression-free survival, disease-free survival for complete responders, overall survival, neuromeningeal relapse rate, and toxicities. Both the safety and efficacy analyses were by intention to treat. Of the 380 patients enrolled, 161 in the R-ACVBP group and 165 in the R-CHOP group completed treatment.
There were no significant differences in the overall response rates at the end of treatment, with 84% of patients who received R-ACVBP having a complete response (CR) or complete response unconfirmed (CRu), and 8% having a partial response (overall response rate, 92%). In the R-CHOP arm, 80% of patients had a CR or CRu, and 8% had a partial response (ORR, 88%).
Grade 3 or 4 hematologic toxicities were more frequent among patients who received R-ACVBP vs. R-CHOP, with neutropenia occurring in 78% vs. 64% and febrile neutropenia in 38% and 9%, respectively; anemia in 35% vs. 5%, and thrombocytopenia in 30% vs. 3%. In addition, 51% of patients in the R-ACVBP arm required red blood cell transfusions, compared with 7% of R-CHOP patients, and 13% required platelet transfusions, compared with 1%.
The only grade 3 or greater general toxicity that occurred in more than 10% of patients was mucositis, which affected 18% of those on R-ACVBP but no patients on R-CHOP. Vomiting, infections, and neurologic toxicities were also more frequent among patients on R-ACVBP, but liver and lung toxicities were identical in the two groups. Cardiotoxicity was seen in 1% of R-CHOP patients, but not among R-ACVBP patients.
In all, 2.6% of patients on R-ACVBP died from toxicities that were attributable to treatment, as did 1.6% of those on R-CHOP.
The study was sponsored by GELA. Dr. Recher had no financial disclosures. Coauthors Dr. Bertrand Coiffier, Dr. Christian Gisselbrecht, and Dr. Andre Bosly disclosed receiving honoraria, research funding, and/or serving in an advisory role to Roche, maker of rituximab.