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