Combination treatment with Velcade (bortezomib) and Thalomid (thalidomide) may significantly improve survival of multiple myeloma patients who received a stem cell transplant, according to recent results of a Phase 3 trial.
The study, “Bortezomib And Thalidomide Maintenance After Stem-Cell Transplantation For Multiple Myeloma: A PETHEMA/GEM trial,” was published in the journal Leukemia.
The standard care for younger patients with newly diagnosed myeloma is treatment with high-dose Alkeran (melphalan) followed by a transplant with the patient’s own stem cells (autologous stem cell transplant, or ASCT). But most patients relapse after this treatment, revealing that better post-transplant or maintenance treatments are necessary to improve patients’ outcomes.
The Spanish Myeloma Group (PETHEMA/GEM) conducted a study with myeloma patients to investigate the effect of maintenance therapies with different drug combinations. They were particularly interested in seeing how bortezomib and thalidomide, which had been tested in previous clinical trials with controversial results, could help myeloma patients.
The GEM05MENOS65 Phase 3 trial enrolled 390 patients ages 65 and younger with newly diagnosed myeloma who were randomized to receive induction treatment with thalidomide/dexamethasone (TD), bortezomib/thalidomide/dexamethasone (VTD), or VBMCP/VBAD/bortezomib (VBMCP/VBAD/B).
Induction treatment is usually given to myeloma patients to reduce the number of cancer cells in circulation before they receive a stem cell transplant.
After 24 weeks of induction therapy, patients then received high-dose Alkeran followed by autologous stem cell transplant.
Three months after this treatment, 271 patients with at least stable disease were randomized to receive maintenance therapy with either thalidomide/bortezomib (TV, 91 patients), thalidomide (T, 88 patients) or alfa-2b-interferon (alfa2-IFN, 92 patients). Alfa2-IFN has been used a maintenance therapy in a number of trials, but was only associated with a survival benefit of four to seven months.
Results indicated that patients receiving maintenance therapy had a higher rate of complete response than those who did not. In particular, the complete response rate was improved by 21% in the TV group, 11% in the T group, and 17% in the alfa2-IFN group.
After a median follow-up of 58.6 months, the progression-free survival (PFS) was significantly longer in patients treated with thalidomide/bortezomib (TV, 50.6 months) compared to those receiving thalidomide only (T, 40.3 months) or alfa2-IFN (32.5 months). Overall survival, however, was not different among the three groups.
Regarding treatment toxicity, grade 2/3 peripheral neuropathy (injury in motor neurons of the arms and legs) was found in 48.8% of patients in the TV group, 34.4% of patients in the T group and in 1% in the alfa2-IFN group.
“Our results showed that maintenance combining thalidomide with … bortezomib (TV) resulted in a significant prolongation of PFS in comparison with T alone or IFN with manageable toxicity,” the researchers concluded.