Three-Drug Regimens Considered Standard in Multiple Myeloma Salvage Therapy

Suzanne Lentzsch, MD, PhD, Columbia University Medical Center (New York, NY), presented data that three drug regimens should be considered standard for myeloma salvage therapy at the 2018 Great Debates and Updates in Hematologic Malignancies meeting (April 13-14, 2018, New York, NY).

Dr Lentzsch presented general principles for selecting treatment for relapsed or refractory myeloma in the rehab setting. The duration of initial response defines the biology of the disease; patients who relapse within a year after transplant usually have a poor prognosis. 

Additionally, triplets are preferred over the doublet in the healthier patient population. Performance status, age, and comorbidities should be considered when choosing the best therapy for the individual patient, as well as prior and residual toxicities. Patients should be treated to a maximum response and maintain one or more agents until progression or tolerability.

Dr Lentzsch explained a series of trials in which triplets have shown promising result in patients with multiple myeloma. The phase III POLLUX trial demonstrated a 63% reduction in the risk of disease progression or death with the addition of daratumumab to lenalidomide and dexamethasone vs lenalidomide and dexamethasone alone. The phase III CASTOR trial showed a 33.8% increase in progression free survival (PFS) with the addition of daratumumab to bortezomib and dexamethasone vs bortezomib and dexamethasone alone.

She also presented data on the phase III ELOQUENT-2 trial, which showed a 27% reduction in the risk of disease progression or death and relative improvement of PFS with the addition of elotuzumab to lenalidomide and dexamethasone vs lenalidomide and dexamethasone alone.

These trials support the use of triplets in multiple myeloma treatment compared with doublets and quadruplets. There is currently no phase II or III trials on quadruplets in relapse or refractory myeloma, although there are ongoing phase I trials, she noted.

Dr Lentzsch concluded her argument by reiterating that three-drug combination regimens provide maximum benefit with excellent quality of life, and the superiority of triplets has been shown in many clinical trials. 

“There are no randomized trials showing that four-drug regimens are better than three-drug regimens in multiple myeloma and four-drug regimens should only be tested in clinical trials,” concluded Dr Lentzsch.—Janelle Bradley