Written in Blood
Hydroxyurea Treatment Impairs
Spermatogenesis in Men With SCA
The prognosis for patients living with
sickle cell anemia (SCA) has improved in
the past few decades, thanks in part to the
availability of hydroxyurea – one of two
therapies approved by the U.S. Food and
Drug Administration for the treatment of
this blood disorder. However, this mainstay
of SCA treatment may have detrimental
effects on fertility for adult male patients
with SCA, according to research published
in Blood.
In a prospective, multicenter study,
Isabelle Berthaut, PhD, from the Assistance
Publique-Hôpitaux de Paris at the Universität
Paris in France, and co-authors assessed the
effects of six months of hydroxyurea treat-
ment on total sperm count (TSC) in 35 men
with severe SCA, finding that “hydroxyurea
… causes significant, rapid, and unpredictable
impairment of spermatogenesis in treated
men.”
Patients were recruited from two
sickle cell referral centers and one
internal medicine department. Patients
were excluded if they had a history of
gonadotoxic treatment or any other
situation that impacted spermatogenesis.
Hydroxyurea was taken orally at
doses ranging from 15 to 30 mg/kg/day.
“All participants appeared adherent to
hydroxyurea therapy,” the researchers
noted, based on patient questionnaires
and analysis of hematologic parameters
(defined as decrease in white blood cells,
increase in mean corpuscular volume, and
hemoglobin [Hb] and fetal Hb levels).
T:7”
REVLIMID ® [lenalidomide] capsules, for oral use
Table 5: All Adverse Reactions in ≥5.0% and Grade 3/4 Adverse Reactions in ≥ 1.0% of Patients in the REVLIMID Vs Placebo Arms*
Maintenance Study 1
Body System
Adverse Reaction
All Adverse Reactions [a]
REVLIMID
(N=224)
n (%)
Placebo
(N=221)
n (%)
Maintenance Study 2
Grade 3/4 Adverse
Reactions [b]
REVLIMID
(N=224)
n (%)
Placebo
(N=221)
n (%)
All Adverse Reactions [a]
REVLIMID
(N=293)
n (%)
Placebo
(N=280)
n (%)
Grade 3/4 Adverse
Reactions [b]
REVLIMID
(N=293)
n (%)
Placebo
(N=280)
n (%)
Nervous system disorders
Paresthesia e
2 ( 0.9) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 39 ( 13.3) 30 ( 10.7) 1 ( 0.3) 0 ( 0.0)
Peripheral neuropathy* e 34 ( 15.2) 30 ( 13.6) 8 ( 3.6) 8 ( 3.6) 29 ( 9.9) 15 ( 5.4) 4 ( 1.4) 2 ( 0.7)
Headache d 11 ( 4.9) 8 ( 3.6) 5 ( 2.2) 1 ( 0.5) 25 ( 8.5) 21 ( 7.5) 0 ( 0.0) 0 ( 0.0)
Alanine aminotransferase
increased 16 ( 7.1) 3 ( 1.4) 8 ( 3.6) 0 ( 0.0) 5 ( 1.7) 5 ( 1.8) 0 ( 0.0) 1 ( 0.4)
Aspartate aminotransferase
increased d 13 ( 5.8) 5 ( 2.3) 6 ( 2.7) 0 ( 0.0) 2 ( 0.7) 5 ( 1.8) 0 ( 0.0) 0 ( 0.0)
24 ( 10.7) 13 ( 5.9) 16 ( 7.1) 12 ( 5.4) 12 ( 4.1) 1 ( 0.4) 2 ( 0.7) 0 ( 0.0)
Investigations
Metabolism and nutrition disorders
Hypokalemia
Dehydration
Hypophosphatemia d
9 ( 4.0 ) 5 ( 2.3) 7 ( 3.1) 3 ( 1.4) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0)
16 ( 7.1) 15 ( 6.8) 13 ( 5.8) 14 ( 6.3) 0 ( 0.0) 1 ( 0.4) 0 ( 0.0) 0 ( 0.0)
Musculoskeletal and connective tissue disorders
Muscle spasms e 0 ( 0.0) 1 ( 0.5) 0 ( 0.0) 0 ( 0.0) 98 ( 33.4) 43 ( 15.4) 1 ( 0.3) 0 ( 0.0)
Myalgia e 7 ( 3.1) 8 ( 3.6) 3 ( 1.3) 5 ( 2.3) 19 ( 6.5) 12 ( 4.3) 2 ( 0.7) 1 ( 0.4)
Musculoskeletal pain e 1 ( 0.4) 1 ( 0.5) 0 ( 0.0) 0 ( 0.0) 19 ( 6.5) 11 ( 3.9) 0 ( 0.0) 0 ( 0.0)
34 ( 15.2) 19 ( 8.6) 4 ( 1.8) 2 ( 0.9) 4 ( 1.4) 1 ( 0.4) 2 ( 0.7) 0 ( 0.0)
12 ( 5.4) 3 ( 1.3) 1 ( 0.5) 80 ( 27.3) 56 ( 20.0) 0 ( 0.0) 0 ( 0.0)
Hepatobiliary disorders
Hyperbilirubinemia e
Cough e
Dyspnea
23 ( 10.3)
c e
15 ( 6.7) 9 ( 4.1) 8 ( 3.6) 4 ( 1.8) 17 ( 5.8) 9 ( 3.2) 2 ( 0.7) 0 ( 0.0)
Rhinorrhea e 0 ( 0.0) 3 ( 1.4) 0 ( 0.0) 0 ( 0.0) 15 ( 5.1) 6 ( 2.1) 0 ( 0.0) 0 ( 0.0)
Pulmonary embolism c d e 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 3 ( 1.0) 0 ( 0.0) 2 ( 0.7) 0 ( 0.0)
8 ( 3.6) 2 ( 0.9) 5 ( 2.2) 2 ( 0.9) 7 ( 2.4) 1 ( 0.4) 4 ( 1.4) 1 ( 0.4)
Vascular disorders
Deep vein thrombosis* c d %
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome c d e
5 ( 2.2)
0 ( 0.0)
2 ( 0.9)
0 ( 0.0)
3 ( 1.0)
0 ( 0.0)
1 ( 0.3)
0 ( 0.0)
Note: AEs are coded to body system /adverse reaction using MedDRA v15.1. A subject with multiple occurrences of an AE is counted only once in each AE
category.
a All treatment-emergent AEs in at least 5% of patients in the Lenalidomide Maintenance group and at least 2% higher frequency (%) than the Placebo
Maintenance group.
b All grade 3 or 4 treatment-emergent AEs in at least 1% of patients in the Lenalidomide Maintenance group and at least 1% higher frequency (%) than the
Placebo Maintenance group.
c All serious treatment-emergent AEs in at least 1% of patients in the Lenalidomide Maintenance group and at least 1% higher frequency (%) than the
Placebo Maintenance group.
d Footnote “a” not applicable for either study
e Footnote “b” not applicable for either study
@ -ADRs where at least one resulted in a fatal outcome
% - ADRs where at least one was considered to be Life Threatening (if the outcome of the event was death, it is included with death cases)
# - All adverse reactions under Body System of Infections and Infestation except for rare infections of Public Health interest will be considered listed
*Adverse Reactions for combined ADR terms (based on relevant TEAE PTs included in Maintenance Studies 1 and 2 [per MedDRA v 15.1]):
Pneumonias Bronchopneumonia,. Lobar pneumonia, Pneumocystis jiroveci pneumonia, Pneumonia, Pneumonia klebsiella, Pneumonia legionella,
Pneumonia mycoplasmal, Pneumonia pneumococcal, Pneumonia streptococcal, Pneumonia viral, Lung disorder, Pneumonitis
Sepsis: Bacterial sepsis, Pneumococcal sepsis, Sepsis, Septic shock, Staphylococcal sepsis
Peripheral neuropathy: Neuropathy peripheral, Peripheral motor neuropathy, Peripheral senso