Less intensive bortezomib-based regimen safe and effective in elderly with multiple myeloma
Richard Philip

A treatment strategy whereby elderly patients with multiple myeloma received less intensive bortezomib-based drug induction therapy followed by maintenance therapy, was efficacious and had a favorable toxicity profile, Spanish researchers have found.

In a previous randomized trial known as the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA) study, elderly patients with multiple myeloma who received a bortezomib-based regimen (a combination of bortezomib, melphalan and prednisone) had better results for endpoints such as response rates, progression-free survival and overall survival compared to those who received standard treatment for multiple myeloma, which is a combination of melphalan and prednisone. However, toxic effects associated with the bortezomib-based regimen were high. [Lancet 2010, DOI:10.1016/S1470-2045(10)70187-X]

“Bortezomib is a first-in-class proteasome inhibitor with significant activity in almost every stage of myeloma. However, the risks of severe peripheral neuropathy associated with bortezomib pose a dilemma for patients with newly diagnosed myeloma, who in the absence of high-risk features can expect improved survival, often longer than 7-10 years,” said Dr. S. Vincent Rajkumar, from the Division of Hematology at the Mayo Clinic in Rochester, Minnesota, US, in an accompanying comment piece. [Lancet 2010, DOI:10.1016/S1470-2045(10)70199-6]

Researchers conducted the present trial to see whether a less-intensive bortezomib-based regimen (once-a-week dosing as opposed to a twice weekly dosing of bortezomib in VISTA) would be efficacious and less toxic.

“This study shows that bortezomib-based regimens that use an intensive dosing of bortezomib twice per week in the first cycle, to obtain rapid debulking activity, followed by less intensive weekly dosing, are not only well-tolerated but are also an active approach for elderly populations…,” said lead researcher, Dr. Maria-Victoria Mateos from the University Hospital of Salamanca in Spain and colleagues.

Mateos and colleagues designed a two-stage randomized trial – patients received induction treatment in the first stage and maintenance treatment in the second stage. Two-hundred and sixty individuals aged 65 or older with untreated multiple myeloma participated in the trial. The primary endpoint was taken to be the response rate in the induction and maintenance phases.

In the induction treatment phase, patients were randomly assigned to mainly a once-a-week dosing of bortezomib together with prednisone and either the alkylating agent, melphalan (VMP* group, N=130) or the immunomodulatory agent, thalidomide (VTP** group, N=130). The induction therapy schedule consisted of 6 cycles (one 6-week cycle in which patients received bortezomib two times a week and five 5-week cycles in which they received bortezomib once a week).

In the maintenance treatment phase, patients were randomized to receive bortezomib plus either thalidomide (N=91) or prednisone (N=87) for up to 3 years.

“This approach was associated with a reduction in the incidence of grade 3 or worse peripheral neuropathy (8 percent vs. 13 percent in VISTA) and gastrointestinal symptoms (4 percent vs. 19 percent in VISTA), compared with a conventional schedule of VMP.

The most common grade 3 or worse non-hematological toxicity in the VMP group was infection. The VTP group on the other hand had a higher incidence of cardiac events.

Researchers therefore advise physicians to consider giving prophylactic antibiotics to patients at least during the first 3 months of VMP treatment and cardiac screening for elderly patients who might be put on VTP therapy.

No significant difference was observed between the response rates for VMP and VTP regimens. Twenty percent of patients in the VMP group and 28 percent of patients in the VTP group had complete remission in the induction phase. In the maintenance phase, after a median follow-up of 22 months, the complete remission rate was 44 percent for the bortezomib plus thalidomide group and 39 percent in the bortezomib plus prednisone group.

“With the consideration of efficacy, toxic effects, and costs together, we conclude that melphalan is probably preferable to thalidomide for bortezomib-based combination therapy in this setting, and should remain an important component of upfront treatments for elderly patients with multiple myeloma,” the authors wrote.


*VMP: Bortezomib (Velcade), Mephalan and Prednisone

**VTP: Bortezomib (Velcade), Thalidomide and Prednisone