ASH Clinical News ACN_5.2_digital | Page 33

CLINICAL NEWS
overall retention rate was
94.2 percent at three years of
follow-up.
After a median of 2.5 years
of treatment, the average
MTD across all sites was 22.5
mg/kg per day. Hematologic
dose-limiting toxicities (the
study’s primary safety end-
point) occurred in 5.1 percent
of participants, “well below the
protocol-specified 20 percent
threshold,” Dr. Tshilolo said,
adding that toxicity was similar
between the screening period
and the treatment phase.
After 12 months of hydroxy-
urea treatment, participants
experienced improvements in
several laboratory variables,
including increases in hemo-
globin (Hb), fetal Hb, and
mean corpuscular volume
and decreases in neutrophil,
reticulocyte, and platelet counts
( TABLE 2 ). These benefits were
sustained through three-year
follow-up.
Improvements in labora-
tory parameters translated to
clinical benefits for children
who received hydroxyurea, the
researchers reported.
TABLE 2.
Laboratory Effects of Hydroxyurea Treatment
Variable
Change from Month 0 to Month 12 (95% CI)
Hemoglobin (g/dL)
+1.0 (0.8-1.0)
Mean corpuscular volume (fl)
Fetal hemoglobin (g/dL)
White cells per mm 3
Absolute neutrophil count per mm 3
Platelets per mm 3
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*
Body System
Adverse Reaction
All Adverse Reactions [a]
REVLIMID
(N=224)
n (%)
Placebo
(N=221)
n (%)
Infections and infestations #
Lower respiratory tract
6 ( 2.7)
1 (
infection bacterial d
Bacteremia d
5 ( 2.2)
0 (
Herpes zoster c d
11 ( 4.9)
10 (
Sepsis* c d @
2 ( 0.9)
1 (
Gastrointestinal disorders
Diarrhea
122 ( 54.5)
83 (
Nausea e
33 ( 14.7)
22 (
Vomiting
17 ( 7.6)
12 (
Constipation e
12 ( 5.4)
8 (
Abdominal pain e
8 ( 3.6)
7 (
Abdominal pain upper e
0 ( 0.0)
0 (
General disorders and administration site conditions
Asthenia
0 ( 0.0)
1 (
Fatigue
51 ( 22.8)
30 (
Pyrexia e
17 ( 7.6)
10 (
Skin and subcutaneous tissue disorders
Dry skin e
9 ( 4.0)
4 (
Rash
71 ( 31.7)
48 (
Pruritus
9 ( 4.0)
4 (
Nervous system disorders
Paresthesia e
2 ( 0.9)
0 (
Peripheral neuropathy* e
34 ( 15.2)
30 (
Headache d
11 ( 4.9)
8 (
Investigations
Alanine aminotransferase
16 ( 7.1)
3 (
increased
Aspartate aminotransferase
increased d
13 ( 5.8)
Metabolism and nutrition disorders
Hypokalemia
24 ( 10.7)
Dehydration
9 ( 4.0 )
Hypophosphatemia d
16 ( 7.1)
Musculoskeletal and connective tissue disorders
Muscle spasms e
0 ( 0.0)
Myalgia e
7 ( 3.1)
Musculoskeletal pain e
1 ( 0.4)
Hepatobiliary disorders
Hyperbilirubinemia e
34 ( 15.2)
Respiratory, thoracic and mediastinal disorders
Cough e
23 ( 10.3)
Dyspnea c e
15 ( 6.7)
Rhinorrhea e
0 ( 0.0)
Pulmonary embolism c d e
0 ( 0.0)
Maintenance Study 2
Grade 3/4 Adverse
Reactions [b]
REVLIMID
(N=224)
n (%)
All Adverse Reactions [a]
Placebo
(N=221)
n (%)
Grade 3/4 Adverse
Reactions [b]
REVLIMID
(N=293)
n (%) Placebo
(N=280)
n (%) REVLIMID
(N=293)
n (%) Placebo
(N=280)
n (%)
0.5) 4 ( 1.8) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0)
0.0)
4.5)
0.5) 4 ( 1.8)
3 ( 1.3)
0 ( 0.0) 0 ( 0.0)
2 ( 0.9)
0 ( 0.0) 0 ( 0.0)
29 ( 9.9)
6 ( 2.0) 0 ( 0.0)
25 ( 8.9)
1 ( 0.4) 0 ( 0.0)
6 ( 2.0)
4 ( 1.4) 0 ( 0.0)
2 ( 0.7)
1 ( 0.4)
7.7)
4.5)
2.3)
0.0)
1.8)
0.0) 114 ( 38.9)
31 ( 10.6)
16 ( 5.5)
37 ( 12.6)
31 ( 10.6)
20 ( 6.8) 34 ( 12.1)
28 ( 10.0)
15 ( 5.4)
25 ( 8.9)
15 ( 5.4)
12 ( 4.3) 7 (
0 (
1 (
2 (
1 (
1 ( 0 (
0 (
0 (
0 (
1 (
0 (
37.6)
10.0)
5.4)
3.6)
3.2)
0.0) 22 (
16 (
8 (
0 (
1 (
0 ( 0.5)
13.6)
4.5) 0 ( 0.0)
21 ( 9.4)
2 ( 0.9) 0 ( 0.0)
9 ( 4.1)
2 ( 0.9) 87 ( 29.7)
31 ( 10.6)
60 ( 20.5) 53 ( 18.9)
15 ( 5.4)
26 ( 9.3) 10 ( 3.4)
3 ( 1.0)
1 ( 0.3) 2 ( 0.7)
0 ( 0.0)
0 ( 0.0)
1.8)
21.7)
1.8) 0 ( 0.0)
11 ( 4.9)
3 ( 1.3) 0 ( 0.0)
5 ( 2.3)
0 ( 0.0) 31 ( 10.6)
22 ( 7.5)
21 ( 7.2) 21 ( 7.5)
17 ( 6.1)
25 ( 8.9) 0 ( 0.0)
3 ( 1.0)
2 ( 0.7) 0 ( 0.0)
0 ( 0.0)
0 ( 0.0)
0.0)
13.6)
3.6) 0 ( 0.0)
8 ( 3.6)
5 ( 2.2) 0 ( 0.0)
8 ( 3.6)
1 ( 0.5) 39 ( 13.3)
29 ( 9.9)
25 ( 8.5) 30 ( 10.7)
15 ( 5.4)
21 ( 7.5) 1 ( 0.3)
4 ( 1.4)
0 ( 0.0) 0 ( 0.0)
2 ( 0.7)
0 ( 0.0)
1.4) 8 ( 3.6) 0 ( 0.0) 5 ( 1.7) 5 ( 1.8) 0 ( 0.0) 1 ( 0.4)
5 ( 2.3) 6 ( 2.7) 0 ( 0.0) 2 ( 0.7) 5 ( 1.8) 0 ( 0.0) 0 ( 0.0)
13 ( 5.9)
5 ( 2.3)
15 ( 6.8) 16 ( 7.1)
7 ( 3.1)
13 ( 5.8) 12 ( 5.4)
3 ( 1.4)
14 ( 6.3) 12 ( 4.1)
0 ( 0.0)
0 ( 0.0) 1 ( 0.4)
0 ( 0.0)
1 ( 0.4) 2 ( 0.7)
0 ( 0.0)
0 ( 0.0) 0 ( 0.0)
0 ( 0.0)
0 ( 0.0)
1 ( 0.5)
8 ( 3.6)
1 ( 0.5) 0 ( 0.0)
3 ( 1.3)
0 ( 0.0) 0 ( 0.0)
5 ( 2.3)
0 ( 0.0) 98 ( 33.4)
19 ( 6.5)
19 ( 6.5) 43 ( 15.4)
12 ( 4.3)
11 ( 3.9) 1 ( 0.3)
2 ( 0.7)
0 ( 0.0) 0 ( 0.0)
1 ( 0.4)
0 ( 0.0)
19 ( 8.6) 4 ( 1.8) 2 ( 0.9) 4 ( 1.4) 1 ( 0.4) 2 ( 0.7) 0 ( 0.0)
12 (
9 (
3 (
0 ( 3 (
8 (
0 (
0 ( 1 (
4 (
0 (
0 ( 0.5)
1.8)
0.0)
0.0) 80 ( 27.3)
17 ( 5.8)
15 ( 5.1)
3 ( 1.0) 56 ( 20.0)
9 ( 3.2)
6 ( 2.1)
0 ( 0.0) 0 (
2 (
0 (
2 ( 0 (
0 (
0 (
0 (
2 ( 0.9) 7 ( 2.4) 1 ( 0.4)
5.4)
4.1)
1.4)
0.0)
9.8)
7.1)
3.6)
0.0)
0.4)
0.0)
1.3)
3.6)
0.0)
0.0)
17 (
10 (
5 (
0 (
4 (
0 (
2.4)
0.0)
0.3)
0.7)
0.3)
0.3)
0.0)
0.7)
0.0)
0.7)
0.0)
0.0)
0.0)
0.0)
0.4)
0.0)
0.0)
0.0)
0.0)
0.0)
Vascular disorders
Deep vein thrombosis* c d %
8 ( 3.6)
2 ( 0.9)
5 ( 2.2)
4 ( 1.4)
1 ( 0.4)
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.
Cosmos Communications
1
Q1
Q2
+12.5 (11.8-13.1)
–6,300 (–6,900 to –5,600)
–2,500 (–2,700 to –2,200)
–67,600 (–82,000 to –52,000)
REVLIMID [lenalidomide] capsules, for oral use
Maintenance Study 1
+13 (12-13)