CLINICAL NEWS
On Location
Conference Coverage
INNOVATION IN HEMATOLOGY
he European Hematology Association’s 21st Congress was held in Copenhagen, Denmark, with a theme of “innovation in hematology.” International hematologists met to share the latest results from clinical and
translational research in hematolgic disorders and emerging techniques for
diagnosis and risk assessment.
Here, ASH Clinical News presents highlights from the meeting, including inotuzumab in acute lymphocytic leukemia, the timing of safely stopping tyrosine
kinase inhibitors in chronic myeloid leukemia, and the efficacy of caplacizumab in
thrombocytopenic purpura.
POLLUX Trial: Triplet Daratumumab
Combination Reduces Risk of
Disease Progression in Relapsed/
Refractory Myeloma
Combining the anti-CD38 antibody
daratumumab with lenalidomide and
dexamethasone led to a lower risk of
disease progression and death, compared with lenalidomide and dexamethasone alone, according to results from
the phase III POLLUX trial of patients
with relapsed/refractory multiple myeloma (RRMM).
“Daratumumab induced deep responses when combined with standard
of care, more than doubling rates of
complete response in these previously
treated patients,” POLLUX investigator
Meletios A. Dimopoulos, MD, from
the National and Kapodistrian University of Athens School of Medicine in
Greece, said during his presentation of
the results at the European Hematology
Association’s 21st Congress. “These
striking results underscore the potential
clinical benefit of daratumumab as a
backbone treatment option for patients who had received one or more
prior lines of therapy.”
The open-label, randomized POLLUX trial compared safety and efficacy
of lenalidomide and dexamethasone
with or without daratumumab in 569
patients with RRMM (median age = 65
years) who had received one or more
prior therapies, were not refractory to
previous lenalidomide, and had a creatinine clearance ≥30 mL/min. Patients
were randomized 1:1 to receive either:
• daratumumab 16 mg/kg
(administered once weekly for 8
weeks, once every 2 weeks for 16
weeks, then once every 4 weeks
until disease progression) plus
lenalidomide 25 mg (administered
ASHClinicalNews.org
orally on days 1-21 of each 28-day
cycle) and dexamethasone 40 mg
administered weekly (DRd; n=286)
• lenalidomide and dexamethasone
alone in the same dosing and
schedule (Rd; n=283)
Patients in the Rd arm could receive
daratumumab if their disease had
progressed.
Patients were treated with a median
of one prior line of therapy (range =
1-11 therapies); 19 percent were treated
with three or more prior therapies.
Most patients (86%) were treated with
a proteasome inhibitor (PI), while 55
percent received a prior immunomodulatory drug (IMiD). Eighteen percent
were treated previously with lenalidomide, while 44 percent received both
a PI and IMiD. Overall, 27 percent of
patients were refractory to the most
recent line of therapy, with 18 percent
refractory to a PI.
After a median follow-up of 13.5
months, DRd significantly improved
patients’ median progression-free
survival (PFS; primary endpoint): the
median PFS in the DRd group was not
reached, compared with 18.4 months
in the Rd arm (p<0.0001), translating
to a 63 percent reduced risk of disease
progression or death compared with Rd
(hazard ratio = 0.37; 95% CI 0.27-0.52;
p<0.0001). Pre-specified subgroup
analyses demonstrated that the PFS benefit with daratumumab was consistent
among patient subgroups.
Similarly, overall survival at 18
months (a secondary endpoint) was
higher for daratumumab-treated
patients: 86 percent for DRd and 76
percent for Rd.
In addition to meeting the
primary endpoint of improved PFS,
daratumumab led to a higher overall
response rate (ORR; secondary endpoint), more than doubling the rate of
complete responses or better:
• ORR: 93% vs. 76% (p<0.0001)
• very good partial response or
better: 76% vs. 44% (p<0.0001)
• complete response or better: 43%
vs. 19% (p<0.0001)
The median duration of response
was longer in the DRd group (not
reached vs. 17.4 months) and the
median time to response was shorter
(1 month vs. 1.3 months), though p
values were not provided.
The most common treatmentrelated adverse events (AEs; occurring
in <25% of patients) in the DRd and
Rd groups included neutropenia (59%
vs. 43%), diarrhea (43% vs. 25%),
fatigue (35% vs. 28%), upper respiratory tract infection (32% vs. 21%),
anemia (31% vs. 35%), constipation
(29% vs. 25%), cough (29% vs. 13%),
thrombocytopenia (27% for each),
and muscle spasms (26% vs. 19%).
Grade 3/4 infections occurred in 28
percent of DRd-treated patients and
23 percent of Rd-treated patients – the
most common of which was pneumonia (8% for each treatment arm).
Infusion-related reactions occurred
in 48 percent of DRd-treated patients
during the first infusion and were
Attendees at the European Hematology Association’s
21st Annual Congress
mostly grade 1/2.Treatment discontinuation due to AEs (n=198) was similar
between the DRd and Rd groups (7% vs.
8%), the investigators noted.
“Daratumumab
more than
doubled rates
of complete
response in
previously
treated patients.”
—MELETIOS A. DIMOPOULOS, MD
Daratu