Defining drug/drug class refractoriness vs lines of therapy in relapsed/refractory multiple myeloma
Utkarsh Goel, Charalampos Charalampous, Prashant Kapoor, Moritz Binder, Francis K. Buadi, David Dingli, Angela Dispenzieri, Amie Fonder, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Miriam Hobbs, Yi L. Hwa, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Rahma Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Abstract
Prior treatments in multiple myeloma (MM) have traditionally been described using lines of therapy (LOT) [ 1 ]. A LOT is defined as one or more complete cycles of a single/combination of agents, or a planned sequential therapy consisting of several regimens [ 1 ]. The number of LOT that a patient has received does influence outcomes seen with subsequent therapies [ 1 , 2 , 3 ], and has been used to determine inclusion in clinical trials for relapsed/refractory multiple myeloma (RRMM) [ 4 , 5 , 6 , 7 , 8 , 9 ]. It has been considered as a reliable measure of prior treatments and is often used to compare results from different treatment regimens, and to guide approval of new agents for the treatment of MM. However, classification based on LOT is prone to several limitations. Although RRMM trials have considered LOT for stratifying patients [ 5 , 6 , 7 , 8 , 9 ], this practice assumes a uniform definition for lines of therapy [ 1 , 10 ]. In reality, patients with the same number of prior lines might have received vastly different regimens, a heterogeneity that will only grow with an increasing number of available drugs. This limits the ability to compare results across different RRMM trials. Further, a LOT can change for several reasons other than disease progression—e.g., toxicity, end of planned therapy, inadequate response to therapy, etc. [ 1 ]; which are more dependent on practice patterns than disease biology. The increasing number of treatment options and different permutations and combinations of drugs makes it difficult to understand the actual significance of the number of prior lines received, owing to variability in what constitutes a line [ 11 ]. We hypothesized that a more meaningful and reliable way would be to define prior therapy by the number of drugs or the number of drug classes that a patient is refractory to, which could better reflect the disease biology.