The replacement of vincristine with Velcade (bortezomib) in the R-CHOP regimen for the treatment of transplantation-ineligible patients with newly diagnosed mantle cell lymphoma improved overall survival in a final analysis of the LYM-3002 trial.
The replacement of vincristine with Velcade (bortezomib) in the R-CHOP regimen for the treatment of transplantation-ineligible patients with newly diagnosed mantle cell lymphoma improved overall survival, according to study results published in The Lancet.
In addition, the new regimen, called VR-CAP, demonstrated a predictable and manageable safety profile, and was associated with a reduced need for subsequent therapies.
“Mantle cell lymphoma, an uncommon hematological malignancy, is associated with poor long-term survival despite initial favorable responses to treatment and evolving treatment modalities,” the researchers wrote. “Although stem-cell transplantation is indicated in some specific patient groups, most patients with mantle cell lymphoma are ineligible for the procedure.”
Currently, frontline R-CHOP [Rituxan (rituximab), cyclophosphamide, doxorubicin, vincristine and prednisone] is the is the standard of care for older patients (aged 65 years or older) who are ineligible for stem-cell transplantation or intensive chemotherapy; however, survival outcomes remain inadequate.
Meanwhile, in a phase 2, prospective, multicenter, single-group, three-stage study, Velcade monotherapy was associated with durable responses and prolonged time to alternative therapy in patients with relapsed or relapsed, refractory mantle cell lymphoma.
Therefore, in the multicenter, randomized phase 3 LYM-3002 trial — designed to evaluate the efficacy and safety of VR-CAP compared with R-CHOP – primary results based on data from before the cutoff date showed a significant improvement in median progression-free survival among those who were treated with Velcade (24.7 vs. 14.4 months).
In the journal article, the researchers offered results from the of the LYM-3002 study.
Between May 22, 2008, and Dec. 5, 2011, the researchers randomized 487 patients 1:1 to receive six or eight 21-day cycles of VR-CAP (or R-CHOP. Both regimens included 375 mg/m2 of intravenous (IV) Rituxan, 750 mg/m2 of IV cyclophosphamide, 50 mg/m2 of IV doxorubicin plus 100 mg/m2 of oral prednisone, while the VR-CAP arm received 1.3 mg/m2 of Velcade and the R-CHOP arm was given 1.4 mg/m2 of vincristine.
The follow-up analysis included 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group), plus patients with data available after the primary analysis clinical cutoff date of Dec. 2, 2013.
After a median follow-up of 82 months, the patients treated with VR-CAP demonstrated a significantly longer median overall survival compared with the R-CHOP group (90.7 vs. 55.7 months).
The researchers discovered three new side effects that were reported since the primary analysis cutoff: one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group.
In total, 103 (42 percent) of the 243 patients in the VR-CAP group and 138 (57 percent) of the 244 in the R-CHOP group died. The most common cause of death was progressive disease.
“Our findings support further asessment of VR-CAP in patients with mantle cell lymphoma, and suggest that combining bortezomib with newer drugs could be of clinical interest,” the researchers concluded.