ASH Clinical News ACN_5.1_Digital - Page 26

On Location 2018 ASH Annual Meeting even further in this analysis, from a historical NNT of 50 to 26. In a prespecified analysis of all-cause mortality and composite primary outcome, the researchers also noted a “substantial 6.4-percent absolute risk reduction” with rivaroxaban, compared with placebo. “This adds to the potential clinical benefit observed [with] this primary prevention approach,” Dr. Khorana observed. “With any primary prevention approach, safety is key, and thankfully we did not observe abnormal safety signals,” Dr. Khorana reported. Incidence of the primary safety endpoint of major bleeding and clinically relevant non-major bleeding among any patients treated with a study drug was “quite low” in each arm: • major bleeding: 1.98% for rivaroxaban vs. 0.99% for placebo (HR=1.96; 95% CI 0.59-6.49; p=0.265) • clinically relevant non-major bleeding: 2.72% vs. 1.98% (HR=1.34; 95% CI 0.54-3.32; p=0.532) Alok A. Khorana, MD, presents CASSINI results at the 2018 ASH Annual Meeting. The trial did not meet its primary efficacy endpoint for thrombotic prevention in the entire intent-to-treat population (which included all randomized patients): The composite outcome occurred in 25 of 420 rivaroxaban- treated patients (5.95%) and 37 of 421 placebo-treated patients (8.79%), for a hazard ratio (HR) of 0.66 (95% CI 0.40-1.09; p=0.10) and a number needed to treat (NNT) of 35. Of all patients with VTE, 38.7 percent of events oc- curred after patients discontinued study drug, which “was [expected], because we know that patients not taking the drug won’t experience thrombotic prevention,” Dr. Khorana said. This finding also confirmed that a Khorana score ≥2 identified a “truly high-risk” population, given the thrombotic rate of 17 percent. However, when the analyses were restricted to the “on-treatment” period, which was an average of 4.5 months for all participants, the primary endpoint oc- curred in significantly fewer rivaroxaban-treated patients (n=11/420; 2.62%), compared with placebo-treated patients (n=27/421; 6.41%). These data suggest that rivar- oxaban treatment was associated with a 60-percent lower risk of thrombotic events (HR=0.4; 95% CI 0.20-0.80; p=0.007). The NNT to prevent thrombotic risk dropped One patient in the rivaroxaban arm experienced a fatal bleeding event. The study was limited by the failure to achieve the primary efficacy endpoint, but Dr. Khorana noted that this was largely because patients remained at high throm- botic risk after stopping the study drug. “Future recom- mendations regarding primary prevention of thrombotic events in cancer should be informed by the findings of this study,” he concluded. The authors report financial relationships with Bayer and Janssen, which provided support for the study. REFERENCE Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban thromboprophylaxis in high-risk ambula- tory cancer patients receiving systemic therapy: results of a randomized clinical trial (CASSINI). Abstract #LBA-1. Presented at the 2018 ASH Annual Meeting, December 4, 2018; San Diego, CA. Is Daratumumab Plus Lenalidomide-Dexamethasone a New Standard for Transplant-Ineligible Myeloma? Adding daratumumab to standard combination of lenalidomide and dexametha- sone (Rd) reduced the risk of disease progression and death by 44 percent in patients with newly diagnosed multiple myeloma (MM) who were ineligible for transplantation, according to results from the phase III MAIA trial. This com- bination also was associated with a greater response rate and deeper responses, compared with Rd alone. “The results from this study are enough to establish daratumumab plus Rd as a new standard of care for patients who are ineligible for transplant,” said Thierry Facon, MD, from the Hôpital Claude Huriez in Lille, France, during his presentation of the results at the 2018 ASH Annual Meeting. The randomized, open-label trial enrolled 737 adults with previously untreated MM who were considered ineligible for high-dose chemotherapy with autologous stem cell transplantation – primarily due to age (≥65 years) or comorbidities. Participants were stratified according to disease stage (per International Staging System [ISS] stage), region, and age <75 vs. ≥75 years), then randomized 1:1 to receive either: • Rd: lenalidomide 25 mg daily on days 1-21 and dexamethasone 40 mg weekly in 28-day treatment cycles (n=369) • Rd plus daratumumab: 16 mg/kg weekly (n=368) Patient characteristics were well balanced between each arm, Dr. Facon said, 24 ASH Clinical News noting that 44 percent of patients were older than 75 years, which is higher than in other trials of myeloma. Participants’ median age was 73 years (range = 45-90 years). After a median follow-up of 28 months (range = 0-41.4 months), median progression-free survival (PFS; the primary endpoint) was not reached in the daratumumab-plus-Rd group and 31.9 months in the Rd group. The 30-month PFS was 71 percent and 56 percent, respectively, for a hazard ratio of 0.56 in favor of the daratumumab group (95% CI 0.43-0.73; p<0.001). Results of analyses for secondary endpoints (overall response rate [ORR] and minimal residual disease [MRD]) also favored the daratumumab group. For daratumumab, ORR was 93 percent, compared with 81 percent in the Rd group (p<0.001), with a greater number of complete responses in the daratumumab group (48% vs. 25%; p<0.001). MRD-negativity rates (with a sensitivity of 10 -5 ) were 24 percent and 7 percent, respectively (p<0.001). While these are preliminary data, he said, the safety analysis showed that da- ratumumab plus Rd is “gentle” enough for older patients. “The [adverse events] were manageable, and the safety profile was consistent with findings from other studies of daratumumab plus standards of care,” Dr. Facon added. Incidence of grade 3/4 neutropenia and pneumonia was higher in patients treated with the daratumumab combination (50% vs. 35% and 14% vs. 8%, respectively), while incidence of grade 3/4 anemia and thrombocytopenia were more common in the Rd group (20% vs. 12% and 9% vs. 7%). However, p values were not reported for these comparisons. The incidence of infusion-related reactions in the daratumumab arm was “as January 2019