CLINICAL NEWS
Chemotherapy-Free Combination Shows Efficacy in Untreated
Follicular Lymphoma
The randomized, global, phase III RELEVANCE
trial showed that a regimen of lenalidomide and
rituximab (R 2 ) had similar safety and efficacy
to a rituximab-based chemotherapy regimen
(R-chemo) in patients with previously untreated
follicular lymphoma (FL).
This is the first randomized trial to
demonstrate the efficacy of a chemother-
apy-free regimen in this setting, lead au-
thor Nathan Hale Fowler, MD, from the
University of Texas MD Anderson Can-
cer Center, noted during his presentation
at the 2018 ASCO Annual Meeting.
“For most patients with low-grade,
grade 1-3a FL, rituximab plus chemo-
therapy results in very good responses
and prolonged progression-free survival
(PFS),” Dr. Fowler noted. “However, most
of these patients are still at risk of relapse
and remissions are shorter with each
subsequent line of therapy.”
The RELEVANCE trial was designed
as a superiority study evaluating R 2 and
R-chemo in 1,030 patients with advanced,
previously untreated FL. Participants were
randomized 1:1 to receive:
• R 2 : lenalidomide 20 mg/day plus
rituximab 375 mg/m 2 (n=513)
Interim results showed PFS was “nearly iden-
tical” between the two arms, and in prespecified
subgroup analyses this finding persisted regard-
less of age, sex, disease stage, or FLIPI score.
Almost all patients reported some treatment-
emergent adverse events (99% in R 2 and 97% in
T:7”
S:6.75”
EXPLORE THE COVERAGE
OF KOVALTRY ®
Dosing with KOVALTRY ® for routine prophylaxis in adults 1 :
Individualize the patient’s dose based on clinical response
• R-chemo (control arm): investigator
choice of R-CHOP, R-bendamustine,
or R-CVP (n=517)
• 2-year PFS: 84% vs. 87% (hazard
ratio = 1.10; 95% CI 0.85-1.43;
p=0.48)
ASHClinicalNews.org
Regimen
20–40 IU/kg 2x/week or 3x/week
LEOPOLD I trial: KOVALTRY ® PK results (arithmetic mean) 1
PK parameters were measured using chromogenic substrate assay after a single
50-IU/kg dose of KOVALTRY ® in 21 previously treated patients ≥18 years old
The AUC was 2103.4 IU•h/dL
The C max was 133.1 IU/dL
The t 1/2 was 14.2 hours
AUC=area under the curve.
C max =maximum concentration.
LEOPOLD=Long-Term Efficacy Open-Label
Program in Severe Hemophilia A Disease.
PK=pharmacokinetics.
t 1/2 =half-life.
See how KOVALTRY ®
compared with Advate ®
in a cross-over PK study
INDICATIONS
KOVALTRY ® Antihemophilic Factor (Recombinant) is a recombinant human DNA sequence
derived, full length Factor VIII concentrate indicated for use in adults and children with
hemophilia A for:
On-demand treatment and control of bleeding episodes
Perioperative management of bleeding
Routine prophylaxis to reduce the frequency of bleeding episodes
KOVALTRY ® is not indicated for the treatment of von Willebrand disease.
SELECTED IMPORTANT SAFETY INFORMATION
KOVALTRY ® is contraindicated in patients who have a history of hypersensitivity reactions
to the active substance, to any of the excipients, or to mouse or hamster proteins.
Hypersensitivity reactions, including anaphylaxis, are possible with KOVALTRY ® . Early signs
of hypersensitivity reactions, which can progress to anaphylaxis, may include chest or throat
tightness, dizziness, mild hypotension and nausea. Discontinue KOVALTRY ® if symptoms
occur and seek immediate emergency treatment.
Please see additional Selected Important Safety Information on the following pages.
For additional risk and use information, please see Brief Summary on following pages.
• CR/CR unknown (CRu) at 120
weeks: 48% for R 2 vs. 53% for
R-chemo (p=0.13)
Dose
In the R 2 arm, lenalidomide dose was
lowered to 10 mg/day if patients achieved
a complete response (CR). Participants in
each arm received maintenance therapy
with rituximab 375 mg/m 2 every eight
weeks for up to one year.
Baseline characteristics were “fairly
well balanced” between both arms, Dr.
Fowler said, with a similar incidence
of bulky disease (42% and 38%), high-
risk Follicular Lymphoma International
Prognostic Index (FLIPI) score (49% and
48%), and B symptoms (27% and 26%).
As of May 31, 2017 (data cutoff),
more than half of patients in each cohort
completed treatment: 69 percent in the
R 2 cohort and 71 percent in the R-chemo
cohort.
After a median follow-up of 37.9
months (range not reported), superior-
ity for the chemotherapy-free regimen
over chemotherapy-containing regimens
was not established for both co-primary
endpoints:
R-chemo). While the authors reported that the
regimens were to lerable, with 8 percent and 3
percent discontinuing treatment due to toxicity,
they noted that patients in the R-chemo arm ap-
peared to experience more neutropenic events,
including grade 3/4 neutropenia (160 [32%] and