On Location 2018 ASH Annual Meeting
In December 2017, the U.S.
Food and Drug Administration
approved hydroxyurea to reduce
the frequency of painful crises
and the need for blood transfu-
sions in pediatric patients (≥2
years) with SCA – marking the
first approval of hydroxyurea in
a pediatric population. However,
because of hydroxyurea’s poten-
tial immunosuppressive effects, it
was unclear whether the treat-
ment would be safe and effective
in children with SCA living in
Africa, where coexisting condi-
tions such as malaria and other
infectious diseases are endemic,
Dr. Tshilolo explained.
In the REACH trial, investi-
gators evaluated the feasibility,
safety, and benefits of hydroxyurea
treatment in 635 children (age
range = 1-10 years) who had been
diagnosed with SCA and were
treated at one of four sites in An-
gola, Democratic Republic of the
Congo, Kenya, and Uganda.
Twenty-nine patients
withdrew during a two-month
screening period; the remaining
606 patients started hydroxyurea
treatment at a dose of 15 to 20
mg/kg per day for six months
or until hematologic toxicity
was detected. The dose was then
escalated according to weight and
pre-defined laboratory criteria
to determine maximum toler-
ated dose (MTD). A total of 600
people completed three months
of treatment.
Adherence was high among
the study population, the
researchers reported, and the
REVLIMID [lenalidomide] capsules, for oral use
e
Footnote “a” not applicable
Footnote “b” not applicable.
@ - adverse reactions in which at least one resulted in a fatal outcome
% - adverse reactions in which at least one was considered to be life threatening (if the outcome of the reaction was death, it is included with death cases)
*Adverse reactions include in combined adverse reaction terms:
Abdominal Pain: Abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain
Pneumonias: Pneumonia, lobar pneumonia, pneumonia pneumococcal, bronchopneumonia, pneumocystis jiroveci pneumonia, pneumonia legionella,
pneumonia staphylococcal, pneumonia klebsiella, atypical pneumonia, pneumonia bacterial, pneumonia escherichia, pneumonia streptococcal, pneumonia viral
Sepsis: Sepsis, septic shock, urosepsis, escherichia sepsis, neutropenic sepsis, pneumococcal sepsis, staphylococcal sepsis, bacterial sepsis, meningococcal
sepsis, enterococcal sepsis, klebsiella sepsis, pseudomonal sepsis
Rash: Rash, rash pruritic, rash erythematous, rash maculo-papular, rash generalized, rash papular, exfoliative rash, rash follicular, rash macular, drug rash with
eosinophilia and systemic symptoms, erythema multiforme, rash pustular
Deep Vein Thrombosis: Deep vein thrombosis, venous thrombosis limb, venous thrombosis
f
Newly Diagnosed MM - REVLIMID Maintenance Therapy Following Auto-HSCT:
Data were evaluated from 1018 patients in two randomized trials who received at least one dose of REVLIMID 10 mg daily as maintenance therapy after
auto-HSCT until progressive disease or unacceptable toxicity. The mean treatment duration for REVLIMID treatment was 30.3 months for Maintenance
Study 1 and 24.0 months for Maintenance Study 2 (overall range across both studies from 0.1 to 108 months). As of the cut-off date of 1 Mar 2015,
48 patients (21%) in the Maintenance Study 1 REVLIMID arm were still on treatment and none of the patients in the Maintenance Study 2 REVLIMID arm
were still on treatment at the same cut-off date
The adverse reactions listed from Maintenance Study 1 included events reported post-transplant (completion of high-dose melphalan /auto-HSCT), and
the maintenance treatment period. In Maintenance Study 2, the adverse reactions were from the maintenance treatment period only. In general, the most
frequently reported adverse reactions (more than 20% in the REVLIMID arm) across both studies were neutropenia, thrombocytopenia, leukopenia, anemia,
upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, asthenia, muscle spasm and pyrexia. The most
frequently reported Grade 3 or 4 reactions (more than 20% in the REVLIMID arm) included neutropenia, thrombocytopenia, and leukopenia. The serious
adverse reactions lung infection and neutropenia (more than 4.5%) occurred in the REVLIMID arm.
For REVLIMID, the most common adverse reactions leading to dose interruption were hematologic events (29.7%, data available in Maintenance Study 2
only). The most common adverse reaction leading to dose reduction of REVLIMID were hematologic events (17.7%, data available in Maintenance Study 2
only). The most common adverse reactions leading to discontinuation of REVLIMID were thrombocytopenia (2.7%) in Maintenance Study 1 and neutropenia
(2.4%) in Maintenance Study 2.
The frequencies of onset of adverse reactions were generally highest in the first 6 months of treatment and then the frequencies decreased over time or
remained stable throughout treatment.
Table 5 summarizes the adverse reactions reported for the REVLIMID and placebo maintenance treatment arms.
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 (%)
Maintenance Study 2
Grade 3/4 Adverse
Reactions [b]
All Adverse Reactions [a]
Grade 3/4 Adverse
Reactions [b]
Placebo
(N=221)
n (%) REVLIMID
(N=224)
n (%) Placebo
(N=221)
n (%) REVLIMID
(N=293)
n (%) Placebo
(N=280)
n (%) REVLIMID
(N=293)
n (%) Placebo
(N=280)
n (%)
Blood and lymphatic system disorders
Neutropenia c % 177 ( 79.0) 94 ( 42.5) 133 ( 59.4) 73 ( 33.0) 178 ( 60.8) 33 ( 11.8) 158 ( 53.9) 21 ( 7.5)
Thrombocytopenia c % 162 ( 72.3) 101 ( 45.7) 84 ( 37.5) 67 ( 30.3) 69 ( 23.5) 29 ( 10.4) 38 ( 13.0) 8 ( 2.9)
Leukopenia
c
51 ( 22.8) 25 ( 11.3) 45 ( 20.1) 22 ( 10.0) 93 ( 31.7) 21 ( 7.5) 71 ( 24.2) 5 ( 1.8)
Anemia 47 ( 21.0) 27 ( 12.2) 23 ( 10.3) 18 ( 8.1) 26 ( 8.9) 15 ( 5.4) 11 ( 3.8) 3 ( 1.1)
Lymphopenia 40 ( 17.9) 29 ( 13.1) 37 ( 16.5) 26 ( 11.8) 13 ( 4.4) 3 ( 1.1) 11 ( 3.8) 2 ( 0.7)
1 ( 0.4) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 12 ( 4.1) 1 ( 0.4) 7 ( 2.4) 1 ( 0.4)
39 ( 17.4) 34 ( 15.4) 39 ( 17.4) 34 ( 15.4) 7 ( 2.4) 1 ( 0.4) 5 ( 1.7) 1 ( 0.4)
60 ( 26.8) 35 ( 15.8) 7 ( 3.1) 9 ( 4.1) 32 ( 10.9) 18 ( 6.4) 1 ( 0.3) 0 ( 0.0)
Pancytopenia c d %
Febrile neutropenia c
Infections and
infestations #
Upper respiratory tract infection e
Neutropenic infection 40 ( 17.9) 19 ( 8.6) 27 ( 12.1) 14 ( 6.3) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0)
Pneumonias* c % 31 ( 13.8) 15 ( 6.8) 23 ( 10.3) 7 ( 3.2) 50 ( 17.1) 13 ( 4.6) 27 ( 9.2) 5 ( 1.8)
Bronchitis c 10 ( 4.5) 9 ( 4.1) 1 ( 0.4) 5 ( 2.3) 139 ( 47.4) 104 ( 37.1) 4 ( 1.4) 1 ( 0.4)
Nasopharyngitis e 5 ( 2.2) 2 ( 0.9) 0 ( 0.0) 0 ( 0.0) 102 ( 34.8) 84 ( 30.0) 1 ( 0.3) 0 ( 0.0)
Gastroenteritis c 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 66 ( 22.5) 55 ( 19.6) 6 ( 2.0) 0 ( 0.0)
2 ( 0.9) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 44 ( 15.0) 19 ( 6.8) 0 ( 0.0) 0 ( 0.0)
8 ( 3.6) 3 ( 1.4) 0 ( 0.0) 0 ( 0.0) 41 ( 14.0) 26 ( 9.3) 0 ( 0.0) 1 ( 0.4)
0 ( 0.0)
Rhinitis
e
Sinusitis e
Influenza c
8 ( 3.6) 5 ( 2.3) 2 ( 0.9) 1 ( 0.5) 39 ( 13.3) 19 ( 6.8) 3 ( 1.0) Lung infection c 21 ( 9.4) 2 ( 0.9) 19 ( 8.5) 2 ( 0.9) 9 ( 3.1) 4 ( 1.4) 1 ( 0.3) 0 ( 0.0)
Lower respiratory tract infection e 13 ( 5.8) 5 ( 2.3) 6 ( 2.7) 4 ( 1.8) 4 ( 1.4) 4 ( 1.4) 0 ( 0.0) 2 ( 0.7)
Infection c 12 ( 5.4) 6 ( 2.7) 9 ( 4.0) 5 ( 2.3) 17 ( 5.8) 5 ( 1.8) 0 ( 0.0) 0 ( 0.0)
9 ( 4.0) 5 ( 2.3) 4 ( 1.8) 4 ( 1.8) 22 ( 7.5) 17 ( 6.1) 1 ( 0.3) 0 ( 0.0)
Urinary tract infection c d e
(continued)
Cosmos Communications
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