ASH Clinical News July 2016 | Page 47

CLINICAL NEWS Triplet Combination of Daratumumab, Bortezomib, and Dexamethasone Improves Multiple Myeloma Survival Risk for VTE Changes Throughout Myeloma Disease Course In the pivotal, randomized, controlled, phase III CASTOR study, adding daratumumab to bortezomib and dexamethasone (DVd) extended progression-free survival (PFS) and time to progression (TTP) compared with bortezomib and dexamethasone (Vd) alone in patients with relapsed/refractory multiple myeloma (MM). Antonio Palumbo, MD, from the University of Torino in Italy, presented the study’s findings during the Plenary Session at the 2016 ASCO Annual Meeting. “These results are unprecedented in this cancer,” Dr. Palumbo said during his presentation. “It’s clear that we’ll be moving to a three-drug regimen with daratumumab as the standard of care.” THE CASTOR trial included 498 patients who received ≥1 prior lines of therapy. Patients were randomized 1:1 to receive eight cycles of: Nearly one in three patients will experience venous thromboembolism (VTE) within the first year of a multiple myeloma (MM) diagnosis, but new research presented at the 2016 ASCO Annual Meeting found that VTE risk persists and changes throughout the disease process. Results from the study, led by Brea Lipe, MD, from the University of Rochester Medical Center in New York, also suggest that thromboprophylaxis guidelines from the International Myeloma Working Group (IMWG) may need to be adjusted to include VTE risk assessment and prevention later in the disease course. The IMWG VTE prevention guidelines categorize patients as low- or high-risk for VTE, and recommend aspirin for low-risk patients and low-molecular-weight heparin (LMWH) or warfarin for high-risk patients for the first four to six months of myeloma treatment, Dr. Lipe and study authors explained. “Because we understand that there is a risk of clotting, there are guidelines to help try to minimize this risk. These guidelines are derived from anecdotal evidence, [and] from sub-studies of larger therapeutic trials that look at subsets of populations pre-selected for [being] very healthy patients,” Dr. Lipe told ASH Clinical News. “So, the question is, ‘Does this work in the real world, and are we doing enough?’” The authors identified 297 patients with MM and VTE (n=89) and 211 matched controls (patients with MM who had not experienced VTE, matched based on gender, age, and time of diagnosis) from the Healthcare Enterprise Repository for Ontological Narration (HERON) database. The median time from MM diagnosis to VTE was 952 days – years after the IMWG guidelines recommend thromboprophylaxis. “Twenty-five percent of our patients clotted within the first year, but then about 45 percent developed their clot after the two-year mark,” Dr. Lipe added. Patients with a higher risk of VTE were more likely to be prescribed LMWH or warfarin versus aspirin or no prophylaxis (p<0.001). However, thromboprophylaxis guidelines “are not really followed very well,” Dr. Lipe said. “About 60 percent of patients – both in the case and control groups – were what we would consider to be high risk. ... But, of those 60 percent, only about 16 percent ever received the recommended prophylactic for that condition.” The researchers did not identify an association between either