Doublets Match Triplet Regimens in Transplant-Ineligible Myeloma

Use of a VD regimen alone to treat patients with transplant-ineligible multiple myeloma was not inferior to VTD or VMP regimens, according to the UPFRONT trial.

Use of a bortezomib-dexamethasone (VD) regimen alone to treat patients with transplant-ineligible multiple myeloma was not inferior to bortezomib-thalidomide-dexamethasone (VTD) or bortezomib-melphalan-prednisone (VMP), according to the results of the community-based UPFRONT trial, which was published in the Journal of Clinical Oncology.

“The initial hypothesis that the efficacy of VD would be inferior to that of VTD and VMP was not confirmed, highlighting a less-than-expected difference between doublet and triplet therapy,” wrote researcher Ruben Niesvizky, MD, of Weill Cornell Medical College in New York, and colleagues.

These results are important, they wrote, because the population of this study “reflects the patient diversity seen in everyday practice.”

The study included 502 patients who were randomly assigned to 24 weeks of induction VD (n = 168; intravenous bortezomib 1.3 mg/m2, days 1, 4, 8, and 11 plus oral dexamethasone 20 mg, days 1, 2, 4, 5, 8, 9, 11, and 12 [cycles 1 to 4], or 1, 2, 4, and 5 [cycles 5 to 8]), VTD (n = 167; bortezomib and dexamethasone [same as VD regimen] plus oral thalidomide 100 mg, days 1 to 21), or VMP (n = 167; bortezomib [same as previous regimens] plus oral melphalan 9 mg/m2 and oral prednisone 60 mg/m2, days 1 to 4, every other cycle), followed by 25 weeks (five 35-day cycles) of bortezomib maintenance (1.6 mg/m2, days 1, 8, 15, and 22).

With a median follow-up of 42.7 months, the median progression-free survival was 14.7 months for VD, 15.4 months for VTD, and 17.3 months for VMP, none a significant difference. The median overall survival for the regimens was 49.8 months for VD, 51.5 months for VTD, and 53.1 months for VMP.

Similarly, the overall response rates were 73% for VD, 80% for VTD, and 70% for VMP.

Peripheral neuropathy was the most common adverse event seen across all three treatment arms. However, overall, adverse events were more common in patients treated with VTD than with VD or VMP.

“Given that bortezomib was administered twice per week for 2 weeks in 3-week cycles, intravenous bortezomib was used for the first part of induction in UPFRONT, less intensive bortezomib dosing and/or subcutaneous bortezomib may be beneficial for reducing the toxicities (particularly the high rates of peripheral neuropathy) associated with these regimens while maintaining efficacy, an important consideration in elderly persons,” the researchers noted.

They proposed in their conclusion that the efficacy of the different treatment arms is a cumulative effect of increased toxicity and decreased quality of life. Quality of life analyses showed a transitory decrease in the mean global health status scores during induction therapy, with improvement or stabilization thereafter.

“Since UPFRONT, additional bortezomib-based regimens, including bortezomib-cyclophosphamide-dexamethasone and bortezomib-lenalidomide-dexamethasone have shown promising activity in transplantation-eligible patients,” the researchers wrote. “Their evaluation in the nontransplantation setting may be warranted in light of recent results with non–bortezomib-based regimens, including lenalidomide/dexamethasone.”