On Location 2018 ASH Annual Meeting
models, the researchers found that the
new model correctly predicted a patient’s
likelihood of overall survival 74 percent of
the time, while the IPSS and IPSS-R mod-
els correctly predicted survival 66 percent
and 67 percent of the time, respectively.
It also outperformed IPSS and IPSS-R
in predicting transformation to acute
myeloid leukemia (AML; 81% vs. 73% and
73%, respectively).
Given the prognostic significance of
the cytogenetic information, Dr. Nazha
said, “We also questioned whether we
needed the clinical information for prog-
nosis.” After comparing the geno-clinical
model with the predictive accuracy of the
mutations-only or mutations-cytogenetics
model, “we found that the more clinical
characteristics we added to cytogenetic
information, the better the accuracy.”
Ultimately, Dr. Nazha concluded,
“[Our experience shows that] machine
learning and artificial intelligence can
open opportunities for us to translate the
genomic data into useful clinical tools.”
When asked about the exclusion of co-
morbidities and other patient factors from
this model, Dr. Nazha noted that certain
data were not available. He added that
the investigators are looking to include
other clinical variables in future models
that could further improve the prognostic
accuracy.
The authors report no relevant conflicts
of interest.
REFERENCE
Nazha A, Komrokji RS, Meggendorfer M, et al. A personalized prediction
model to risk stratify patients with myelodysplastic syndromes.
Abstract #793. Presented at the 2018 ASH Annual Meeting, December
3, 2018; San Diego, CA.
REVLIMID [lenalidomide] capsules, for oral use
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly
compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Newly Diagnosed MM – REVLIMID Combination Therapy:
Data were evaluated from 1613 patients in a large phase 3 study who received at least one dose of REVLIMID with low dose dexamethasone (Rd) given for
2 different durations of time (i.e., until progressive disease [Arm Rd Continuous; N=532] or for up to eighteen 28-day cycles [72 weeks, Arm Rd18; N=540]
or who received melphalan, prednisone and thalidomide (Arm MPT; N=541) for a maximum of twelve 42-day cycles (72 weeks). The median treatment
duration in the Rd Continuous arm was 80.2 weeks (range 0.7 to 246.7) or 18.4 months (range 0.16 to 56.7).
In general, the most frequently reported adverse reactions were comparable in Arm Rd Continuous and Arm Rd18, and included diarrhea, anemia,
constipation, peripheral edema, neutropenia, fatigue, back pain, nausea, asthenia, and insomnia. The most frequently reported Grade 3 or 4 reactions
included neutropenia, anemia, thrombocytopenia, pneumonia, asthenia, fatigue, back pain, hypokalemia, rash, cataract, lymphopenia, dyspnea, DVT,
hyperglycemia, and leukopenia. The highest frequency of infections occurred in Arm Rd Continuous (75%) compared to Arm MPT (56%). There were more
grade 3 and 4 and serious adverse reactions of infection in Arm Rd Continuous than either Arm MPT or Rd18.
In the Rd Continuous arm, the most common adverse reactions leading to dose interruption of REVLIMID were infection events (28.8%); overall, the
median time to the first dose interruption of REVLIMID was 7 weeks. The most common adverse reactions leading to dose reduction of REVLIMID in the
Rd Continuous arm were hematologic events (10.7%); overall, the median time to the first dose reduction of REVLIMID was 16 weeks. In the Rd Continuous
arm, the most common adverse reactions leading to discontinuation of REVLIMID were infection events (3.4%).
In both Rd arms, 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, except for cataracts. The frequency of onset of cataracts increased over time with 0.7% during the first
6 months and up to 9.6% by the 2nd year of treatment with Rd Continuous.
Table 4 summarizes the adverse reactions reported for the Rd Continuous, Rd18, and MPT treatment arms.
Table 4: All Adverse Reactions in ≥5.0% and Grade 3/4 Adverse Reactions in ≥ 1.0% of Patients in the Rd Continuous or Rd18 Arms*
All Adverse Reactions a
Grade 3/4 Adverse Reactions b
Rd
Rd
Body System
Continuous
Rd18
MPT
Continuous
Rd18
MPT
Adverse Reaction
(N = 532)
(N = 540)
(N = 541)
(N = 532)
(N = 540)
(N = 541)
General disorders and administration site conditions
Fatigue %
173 (32.5)
177 (32.8)
154 (28.5)
39 ( 7.3)
46 ( 8.5)
31 ( 5.7)
Asthenia
150 (28.2)
123 (22.8)
124 (22.9)
41 ( 7.7)
33 ( 6.1)
32 ( 5.9)
Pyrexia c
114 (21.4)
102 (18.9)
76 (14.0)
13 ( 2.4)
7 ( 1.3)
7 ( 1.3)
Non-cardiac chest pain f
29 ( 5.5)
31 ( 5.7)
18 ( 3.3)
<1%
< 1%
< 1%
Gastrointestinal disorders
Diarrhea
242 (45.5)
208 (38.5)
89 (16.5)
21 ( 3.9)
18 ( 3.3)
8 ( 1.5)
Abdominal pain % f
109 (20.5)
78 (14.4)
60 (11.1)
7 ( 1.3)
9 ( 1.7)
< 1%
Dyspepsia f
57 (10.7)
28 ( 5.2)
36 ( 6.7)
<1%
< 1%
0 ( 0.0)
Musculoskeletal and connective tissue disorders
Back pain c
170 (32.0)
145 (26.9)
116 (21.4)
37 ( 7.0)
34 ( 6.3)
28 ( 5.2)
Muscle spasms f
109 (20.5)
102 (18.9)
61 (11.3)
< 1%
< 1%
< 1%
Arthralgia f
101 (19.0)
71 (13.1)
66 (12.2)
9 ( 1.7)
8 ( 1.5)
8 ( 1.5)
Bone pain f
87 (16.4)
77 (14.3)
62 (11.5)
16 ( 3.0)
15 ( 2.8)
14 ( 2.6)
Pain in extremity f
79 (14.8)
66 (12.2)
61 (11.3)
8 ( 1.5)
8 ( 1.5)
7 ( 1.3)
Musculoskeletal pain f
67 (12.6)
59 (10.9)
36 ( 6.7)
< 1%
< 1%
< 1%
Musculoskeletal chest pain f
60 (11.3)
51 ( 9.4)
39 ( 7.2)
6 ( 1.1)
< 1%
< 1%
Muscular weakness f
43 ( 8.1)
35 ( 6.5)
29 ( 5.4)
< 1%
8 ( 1.5)
< 1%
Neck pain f
40 ( 7.5)
19 ( 3.5)
10 ( 1.8)
< 1%
< 1%
< 1%
Infections and infestations
Bronchitis c
90 (16.9)
59 (10.9)
43 ( 7.9)
9 ( 1.7)
6 ( 1.1)
3 ( 0.6)
Nasopharyngitis f
80 (15.0)
54 (10.0)
33 ( 6.1)
0 ( 0.0)
0 ( 0.0)
0 ( 0.0)
Urinary tract infection f
76 (14.3)
63 (11.7)
41 ( 7.6)
8 ( 1.5)
8 ( 1.5)
< 1%
Upper respiratory tract infection c% f
69 (13.0)
53 ( 9.8)
31 ( 5.7)
< 1%
8 ( 1.5)
< 1%
Pneumonia c@
93 (17.5)
87 (16.1)
56 (10.4)
60 ( 11.3)
57 ( 10.5)
41 ( 7.6)
Respiratory tract infection %
35 ( 6.6)
25 ( 4.6)
21 ( 3.9)
7 ( 1.3)
4 ( 0.7)
1 ( 0.2)
Influenza f
33 ( 6.2)
23 ( 4.3)
15 ( 2.8)
< 1%
< 1%
0 ( 0.0)
Gastroenteritis f
32 ( 6.0)
17 ( 3.1)
13 ( 2.4)
0 ( 0.0)
< 1%
< 1%
Lower respiratory tract infection
29 ( 5.5)
14 ( 2.6)
16 ( 3.0)
10 ( 1.9)
3 ( 0.6)
3 ( 0.6)
Rhinitis f
29 ( 5.5)
24 ( 4.4)
14 ( 2.6)
0 ( 0.0)
0 ( 0.0)
0 ( 0.0)
Cellulitis c
< 5%
< 5%
< 5%
8 ( 1.5)
3 ( 0.6)
2 ( 0.4)
Sepsis c@
33 ( 6.2)
26 ( 4.8)
18 ( 3.3)
26 ( 4.9)
20 ( 3.7)
13 ( 2.4)
Nervous system disorders
Headache f
75 ( 4.1)
52 ( 9.6)
56 (10.4)
< 1%
< 1%
< 1%
Dysgeusia f
39 ( 7.3)
45 ( 8.3)
22 ( 4.1)
< 1%
0 ( 0.0)
< 1%
(continued)
Cosmos Communications
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