NEWS
DREAMM-6: Evaluating Belantamab Mafodotin and Bortezomib Plus Dexamethasone
in Relapsed/Refractory Myeloma
Early data from the DREAMM-6 study suggest that the
combination of belantamab mafodotin, bortezomib, and
dexamethasone is active in patients with relapsed or
refractory multiple myeloma (MM). These findings were
presented by Ajay Nooka, MD, of the Winship Cancer
Institute at Emory University in Atlanta, as part of the
ASCO20 Virtual Scientific Program. 1
In the phase II DREAMM-2 study, single-agent anti-
B-cell maturation antigen (BCMA) antibody drug conjugate
belantamab mafodotin resulted in clinical responses
in patients with MM whose disease was refractory to an
immunomodulatory agent, a proteasome inhibitor, and
an anti-CD38 monoclonal antibody. 2
In the DREAMM-6 trial, 52 patients were enrolled
in a two-part, two-arm study of belantamab mafodotin
combined with either bortezomib-dexamethasone
or lenalidomide-dexamethasone. In the part I dose
escalation study, 13 patients were enrolled, while 45
patients were enrolled in the part II dose expansion
study. Dr. Nooka presented results on the bortezomibdexamethasone
arm of the part II dose expansion
study, which included 18 patients.
At data cutoff, patients had been treated with
2.5-mg/kg belantamab mafodotin plus bortezomibdexamethasone
for a median of 18.2 weeks. Grade 3/4
adverse events (AEs) were reported in 89% of patients,
with 28% of patients experiencing AEs leading to
permanent discontinuation of study treatment.
The most common AEs were infusion-related reactions
and thrombocytopenia, as well as corneal events
including keratopathy, blurred vision, and dry eye. Keratopathy
is expected with belantamab mafodotin and was
managed with dose modifications, Dr. Nooka said.
The overall response rate was 78%, with 50% of
patients experiencing at least a very good partial response.
Dr. Nooka noted that duration of response has not yet
been reached. “Findings for the remainder of the study
will be presented at future meetings when data become
mature and available,” he said.
Study authors report relationships with GlaxoSmith-
Kline, the manufacturers of belantamab mafodotin.
References
1. Nooka AK, Stockerl-Goldstein K, Quch H, et al. DREAMM-6: Safety and tolerability of
belantamab mafodotin in combination with bortezomib/dexamethasone in relapsed/
refractory multiple myeloma (RRMM). Abstract 8502. Presented as part of the
ASCO20 Virtual Scientific Program. May 29-31, 2020.
2. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory
multiple myeloma (DREAMM-2): A two-arm, randomized, open-label, phase II study.
Lancet Oncol. 2020 Feb;21:207-221.
ENDURANCE: Comparing KRd With VRd in Newly
Diagnosed Myeloma
Initial treatment with carfilzomib, lenalidomide, and
dexamethasone (KRd) was not associated with longer
progression-free survival (PFS) compared with bortezomib,
lenalidomide, and dexamethasone (VRd) in
patients with newly diagnosed multiple myeloma (MM),
according to findings from the phase III ENDURANCE
trial presented by Shaji Kumar, MD, of Mayo Clinic in
Rochester, Minnesota. The study was a late-breaking
abstract in the ASCO20 Virtual Scientific Program.
The ENDURANCE trial enrolled 1,087 patients with
newly diagnosed MM in the absence of del17p, t(14;16),
and t(14;20), as evidenced by fluorescence in situ
hybridization (FISH) testing on bone marrow, and without
plasma cell leukemia or a high-risk GEP70 profile.
Patients were randomly assigned 1:1 to:
• VRd (n=542): bortezomib 1.3 mg/m 2 on days 1, 4, 8,
and 11 (days 1 and 8 for cycles 9-12), lenalidomide
25 mg on days 1-14, and dexamethasone 40 mg on
days 1, 2, 4, 5, 8, 9, 11, and 12 of a 3-week cycle for a
total of 12 cycles
• KRd (n=545): carfilzomib 36 mg/m 2 on days 1, 2, 8, 9,
15, and 16, lenalidomide 25 mg daily on days 1-21,
and dexamethasone 40 mg weekly, in 4-week cycles
for a total of 9 cycles
Treatment was administered for 36 weeks and was
followed by a second random allocation to indefinite
treatment versus 2 years of maintenance with lenalidomide
15 mg on days 1 to 21 every 4 weeks. The primary
outcome measures included PFS for the induction
analysis and overall survival (OS) for the maintenance
analysis. The maintenance data are not mature and
have not yet been reported.
At time of randomization, the median age of the
overall cohort was 65 years. The median induction
duration for the VRd and KRd groups were 5.9 and
8.2 months, respectively. Disease progression was
observed in 6% of patients randomized to VRd and 4%
of patients randomized to KRd, which was not a statistically
significant difference.
A higher proportion of patients assigned to VRd
experienced an adverse event (17% vs. 9%) and 7% of
patients in the VRd arm withdrew from the study compared
with 4% of patients assigned to KRd. Grade ≥3
non-hematologic toxicities were observed in 42% of
VRd-treated patients and 48% of KRd-treated patients.
A higher proportion of grade ≥3 composite cardiac,
pulmonary, and renal events occurred in the KRd
group (16% vs. 5%). In addition, 8% of patients in the
VRd group experienced grade ≥3 peripheral neuropathy
during treatment compared with 1% of patients in
the KRd group.
Approximately 83% of patients in the VRd group
and 86% of patients in the KRd arm experienced a partial
response or better. A very good partial response or
better was observed in 43% of patients randomized to
VRd and 49% of patients randomized to KRd. A complete
response was experienced by 10% of patients in
the VRd group and 14% of patients in the KRd arm.
The PFS was not significantly different between the
groups at the second of three planned interim analyses
(median PFS for VRd and KRd = 34.4 months vs. 34.6
months, respectively; p=0.74). There were also no differences
between the groups in terms of PFS based on
age (<65 vs. ≥65 years), presence or lack of t(4;14), or
International Staging System stage. In addition, there
was a similar 3-year OS survival rate in the VRd (84%)
and KRd (86%) treatment arms.
Study authors report relationships with Takeda and
Amgen, the manufacturers of bortezomib and carfilzomib,
respectively.
Reference
Kumar S, Jacobus SJ, Cohen AD, et al. Carfilzomib, lenalidomide, and dexamethasone
(KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of
newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial.
AbstractLBA3. Presented as part of the ASCO20 Virtual Scientific Program. May 29-31
2020.
BOSTON: Weekly Combination
Therapy Including Selinexor
Improved PFS in Relapsed/
Refractory Myeloma
Once-weekly combination treatment with selinexor,
bortezomib, and dexamethasone (SVd) led to an
approximately 4-month improvement in progressionfree
survival (PFS) compared with bortezomib plus
dexamethasone (Vd) in patients with relapsed or
refractory multiple myeloma, according to the
results of the phase III BOSTON study. 1 Meletios A.
Dimopoulos, MD, of National and Kapodistrian University
of Athens School of Medicine, Greece, presented
the findings as part of the ASCO20 Virtual
Scientific Program.
Selinexor is an oral, selective inhibitor of XPO1-
mediated nuclear export that, in combination with
dexamethasone, induced a partial response or better
in 26% of 122 patients with relapsed/refractory
myeloma enrolled in the phase Ic/II STORM study
reported in 2019 in the New England Journal of Medicine.
.2
The BOSTON study randomized 402 patients with
1 to 3 prior therapies to either weekly SVd (n=195)
or twice-weekly Vd (n=207). Upon disease progression,
crossover was permitted to SVd for patients who
could continue to tolerate bortezomib or to selinexor
and dexamethasone for those with bortezomib
intolerance.
Overall rates of peripheral neuropathy were significantly
lower with SVd than with Vd (p=0.001).
However, patients assigned to SVd experienced elevated
rates of certain grade 3 or higher adverse
events, including thrombocytopenia (35.9% vs.
17.2%), fatigue (13.3% vs. 1.0%), and nausea (7.7% vs.
0%).
The selinexor combination significantly prolonged
PFS, with a median of 13.9 months compared
with 9.5 months for Vd alone (hazard ratio [HR] = 0.70;
p=0.0066). PFS benefit was seen across all subgroups,
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