Literature Scan
”In terms of predicting
patient outcome, the
MRD testing was more
powerful.” —PROF. DAVID GRIMWADE
just don’t know whether or not they are best served by
having a transplant. It’s a contentious area [and] it’s
uncertain what to do.”
Researchers used a real-time quantitative polymerase-chain-reaction assay to detect MRD in 2,569
samples from 346 patients with NPM1-mutated AML.
They then developed a custom 51-gene panel to perform targeted sequencing of 223 samples at the time
of diagnosis and 49 samples obtained at the time of
relapse. “Molecular profiling highlighted the complexity
of NPM1-mutated AML, with segregation of patients
into more than 150 subgroups, thus precluding reliable
outcome prediction,” the researchers wrote. MRD status
“was more informative,” they added, and was able to
detect trace levels of leukemia cells after chemotherapy.
Fifteen percent of patients had persistent NPM1mutated transcripts following the second chemotherapy
cycle, according to analyisis of the blood samples.
These patients experienced a significantly higher risk of
relapse at three years, compared with patients without
T:7”
without a dose reduction, 50% in the REVLIMID/dexamethasone
treatment group had at least one additional dose interruption with or
without a dose reduction compared to 21% in the placebo/dexamethasone
treatment group. Most adverse reactions and Grade 3/4 adverse reactions
were more frequent in patients who received the combination of
REVLIMID/dexamethasone compared to placebo/dexamethasone.
Table 5: Adverse Reactions Reported in ≥5% of Patients and with a
≥2% Difference in Proportion of Patients Between the
REVLIMID/dexamethasone and Placebo/dexamethasone Groups
System Organ Class/ Preferred Term REVLIMID/Dex* Placebo/Dex *
(N=353)
(N=350)
n (%)
n (%)
Tables 5, 6, and 7 summarize the adverse reactions reported for
REVLIMID/dexamethasone and placebo/dexamethasone groups.
Metabolism and nutrition disorders
Anorexia
Hypokalemia
Hypocalcemia
Appetite Decreased
Dehydration
Hypomagnesemia
Investigations
Weight Decreased
Eye disorders
Blurred vision
Vascular disorders
Deep vein thrombosis%
Hypertension
Hypotension
55 (15.6)
48 (13.6)
31 (8.8)
24 (6.8)
23 (6.5)
24 (6.8)
34 (9.7)
21 (6.0)
10 (2.9)
14 (4.0)
15 (4.3)
10 (2.9)
69 (19.5)
52 (14.9)
61 (17.3)
40 (11.4)
33 (9.3)
28 (7.9)
25 (7.1)
15 (4.3)
20 (5.7)
15 (4.3)
Table 6: Grade 3/4 Ad verse Reactions Reported in ≥2% Patients
and With a ≥1% Difference in Proportion of Patients Between the
REVLIMID/dexamethasone and Placebo/dexamethasone groups
System Organ Class/ Preferred Term REVLIMID/Dex# Placebo/Dex#
(N=353)
(N=350)
n (%)
n (%)
Blood and lymphatic system disorders
Neutropenia%
118 (33.4)
12 (3.4)
Thrombocytopenia@
43 (12.2)
22 (6.3)
Anemia@
35 (9.9)
20 (5.7)
Leukopenia
14 (4.0)
1 (0.3)
Lymphopenia
10 (2.8)
4 (1.1)
Febrile Neutropenia%
8 (2.3)
0 (0.0)
General disorders and administration site conditions
Fatigue
23 (6.5)
17 (4.9)
Vascular disorders
Deep vein thrombosis%
29 (8.2)
12 (3.4)
Infections and infestations
Pneumonia@
30 (8.5)
19 (5.4)
Urinary Tract Infection
5 (1.4)
1 (0.3)
Metabolism and nutrition disorders
Hypokalemia
17 (4.8)
5 (1.4)
Hypocalcemia
13 (3.7)
6 (1.7)
Hypophosphatemia
9 (2.5)
0 (0.0)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism@
14 (4.0)
3 (0.9)
Respiratory Distress@
4 (1.1)
0 (0.0)
Musculoskeletal and connective tissue disorders
Muscle weakness
20 (5.7)
10 (2.9)
Gastrointestinal disorders
Diarrhea@
11 (3.1)
4 (1.1)
Constipation
7 (2.0)
1 (0.3)
Nausea@
6 (1.7)
2 (0.6)
Cardiac disorders
Atrial fibrillation@
13 (3.7)
4 (1.1)
Tachycardia
6 (1.7)
1 (0.3)
Cardiac Failure Congestive@
5 (1.4)
1 (0.3)
Nervous System disorders
Syncope
10 (2.8)
3 (0.9)
Dizziness
7 (2.0)
3 (0.9)
(continued)
Cosmos Communications
K
1
js
QC
T:10”
Table 5: Adverse Reactions Reported in ≥5% of Patients and with a
≥2% Difference in Proportion of Patients Between the
REVLIMID/dexamethasone and Placebo/dexamethasone Groups
System Organ Class/ Preferred Term REVLIMID/Dex* Placebo/Dex *
(N=353)
(N=350)
n (%)
n (%)
Blood and lymphatic system disorders
Neutropenia %
149 (42.2)
22 (6.3)
Anemia@
111 (31.4)
83 (23.7)
Thrombocytopenia@
76 (21.5)
37 (10.6)
Leukopenia
28 (7.9)
4 (1.1)
Lymphopenia
19 (5.4)
5 (1.4)
General disorders and administration site conditions
Fatigue
155 (43.9)
146 (41.7)
Pyrexia
97 (27.5)
82 (23.4)
Peripheral edema
93 (26.3)
74 (21.1)
Chest Pain
29 ( 8.2)
20 (5.7)
Lethargy
24 ( 6.8)
8 (2.3)
Gastrointestinal disorders
Constipation
143 (40.5)
74 (21.1)
Diarrhea@
136 (38.5)
96 (27.4)
Nausea@
92 (26.1)
75 (21.4)
Vomiting@
43 (12.2)
33 (9.4)
Abdominal Pain@
35 (9.9)
22 (6.3)
Dry Mouth
25 (7.1)
13 (3.7)
Musculoskeletal and connective tissue disorders
Muscle cramp
118 (33.4)
74 (21.1)
Back pain
91 (25.8)
65 (18.6)
Bone Pain
48 (13.6)
39 (11.1)
Pain in Limb
42 (11.9)
32 (9.1)
Nervous system disorders
Dizziness
82 (23.2)
59 (16.9)
Tremor
75 (21.2)
26 (7.4)
Dysgeusia
54 (15.3)
34 (9.7)
Hypoaesthesia
36 (10.2)
25 (7.1)
Neuropathyª
23 (6.5)
13 (3.7)
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea
83 (23.5)
60 (17.1)
Nasopharyngitis
62 (17.6)
31 (8.9)
Pharyngitis
48 (13.6)
33 (9.4)
Bronchitis
40 (11.3)
30 (8.6)
Infectionsb and infestations
Upper respiratory tract infection
87 (24.6)
55 (15.7)
Pneumonia@
48 (13.6)
29 (8.3)
Urinary Tract Infection
30 (8.5)
19 (5.4)
Sinusitis
26 (7.4)
16 (4.6)
Skin and subcutaneous system disorders
Rashc
75 (21.2)
33 (9.4)
Sweating Increased
35 (9.9)
25 (7.1)
Dry Skin
33 (9.3)
14 (4.0)
Pruritus
27 (7.6)
18 (5.1)
(continued)