Daratumumab-based combination therapies (DCTs) are ineffective in patients with multiple myeloma who have been heavily pre-treated or are refractory to one or more agents in a DCT, according to a recent study published in American Journal of Hematology (online August 11, 2017; doi:10.1002/ajh.24883).
Experience with DCTs using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma is limited outside of clinical trials.
For their study, Arjun Lakshman, MD, Mayo Clinic (Rochester, MN), and colleagues assessed the outcomes of 126 patients who received 1 or more cycles of a DCT, as well as a median of 4 prior therapies. A total of 17 (13%) patients were refractory to single agent daratumumab. A total of 52 (41%) received DPd, 34 (27%) received DRd, 23 (18%) received DVd, and 17 (14%) received ‘other’ DCTs.
Although the median time to a DCT was 4.3 years, some patients received it within 1 year, while others waited 13 years.
Median patient age at DCT initiation was 67 years. A total of 33% of patients had high-risk cytogenetics. The time from diagnosis to first DCT was 4.3 years. Median follow-up lasted 5.5 months.
The researchers found that the overall response rate had been 47%, and median progression free survival (PFS) had been 5.5 months. Median PFS was 2.2 months in those with penta-refractory multiple myeloma (n= 8), compared with 3.1 months in those with quadruple refractory multiple myeloma (n=18), and 8.9 months in others (n=100). Ultimately, median PFS was worse among patients who were refractory to 1 or more agents used in the DCT (4.9 months) and among those who had received more than 2 prior therapies, compared with others.
The most commonly reported non-hematologic toxicities had been infections (38%), fatigue (32%), and infusion reactions (18%). Additionally, 41% of patients had experienced grade 3 or higher hematological toxicities.
“DCTs are effective in [relapsed/refractory multiple myeloma],” the researchers concluded. “ORR and PFS in heavily pre-treated patients are lower than those reported in clinical trials.”—Christina Vogt