On Location ASH Annual Meeting
samples detected 17 total muta-
tions as clonal hematopoiesis
in 15 patients (23%); during a
median follow-up of 14.8 years,
five patients (7%) developed t-
MNs after a median of 5.4 years
post-treatment.
Clonal hematopoiesis was
detected in four of five patients
(80%) who developed t-MNs and
in 11 of 69 patients (16%) who
did not (p=0.005). The rate of
t-MN development at 10 years
also was significantly higher in
patients with clonal hemato-
poiesis, compared with patients
without (29% [95% CI 12-59] vs.
0%; p=0.001).
Overall, the positive and nega-
tive predictive values of clonal
hematopoiesis in the validation
cohort were 26.7 percent (95% CI
7.8-55.1) and 98.3 percent (95%
CI 90.9-99.9), respectively.
“Genetic mutations that
are present in t-MN leukemia
samples actually could be found
in blood samples obtained at
the time of their original cancer
diagnosis,” Dr. Takahashi added.
“The data suggest potential ap-
proaches of screening for clonal
hematopoiesis in cancer patients
PAGE 2
that may identify patients at risk
of developing t-MNs.”
REFERENCES
• Takahashi K, Wang F, Kantarjian HM, et al. Clonal he-
matopoiesis increases risk of therapy-related myeloid
neoplasms. Abstract #38. Presented at the 2016 ASH
Annual Meeting, December 3, 2016; San Diego, California.
• Takahashi K, Wang F, Kantarjian HM, et al. Preleukae-
mic clonal haemopoiesis and risk of therapy-related
myeloid neoplasms: a case-control study. Lancet Oncol.
2017;18:100-11.
T:1
S:1
Designed with his future in mind
Proven efficacy and safety in adolescents and adults
with prophylaxis using as few as 2 infusions per week 1
LEOPOLD I Trial 1,2
Study description
Multinational, open-label, prospective trial evaluating
pharmacokinetics, efficacy, safety, and perioperative
management of bleeding with KOVALTRY ®
Previously treated male patients (PTPs) aged 12 to 65 years
with severe hemophilia A (<1% FVIII) (n=73) studied for 1 year
Dosing
Dosing regimens were determined by the investigators
to meet individual patients’ needs
2x/week prophylaxis: 20-50 IU/kg (n=18)
3x/week prophylaxis: 20-50 IU/kg (n=44)
Primary
efficacy endpoint
Annualized bleed rate (ABR) at 12 months
(n=62 for efficacy analysis)
After a single 50 IU/kg dose of KOVALTRY ® , the demonstrated
half-life [mean ± standard deviation (SD)] in 26 previously
treated adolescent and adult patients was:
Pharmacokinetics
12 to 17 years
(n=5)
Chromogenic Assay
One-stage Assay
14.4 ± 5.5 hours
11.7 ± 1.1 hours
≥18 years
(n=21)
14.2 ± 3.5 hours
14.3 ± 3.7 hours
LEOPOLD=Long-Term Effi cacy Open-Label Program in Severe Hemophilia A Disease.
SELECTED IMPORTANT SAFETY INFORMATION
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.
KOVALTRY ® may contain trace amounts of mouse and hamster proteins. Patients treated with
this product may develop hypersensitivity to these non-human mammalian proteins.
Please see additional Important Safety Information on following pages.
For additional important risk and use information, please see Brief Summary on following pages.