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AZA or LEN plus AZA in MDS, CMML and low blast AML
only 2.6% cycles dose- reduced. For those on combination treatment the median duration of lenalidomide treatment was 9 cycles (range 1-12) with only 2.8% lenalidomide cycles dose- reduced. Early discontinuation of azacitidine was mainly due to investigator/patient decision, relapse/progressive disease, or death. Early discontinua- tion of lenalidomide was mainly due to toxicity (11 patients) or investigator/patient decision (9 patients). Six patients were treated with lenalidomide after completing the protocol-specified 12 months of study therapy; 2 in AZA arm and 4 in LEN+AZA. This was initiated by indi- vidual investigators, and continued for up to 2 years post study therapy. The extended lenalidomide treatment was associated with grade 3 diarrhea in one patient and result- ed in no improvement in response in these patients.
Safety
Non hematologic toxicity. Rates of all adverse events grade 3 or higher according to system and treatment arm are sum- marised in Online Supplementary Table S1 with no differences observed. The most common non-hematologic toxicity was infection; the overall number of infectious episodes grade 3 or worse was 132 in 42.8% patients.
There was no difference between the arms for overall rates of infection with sepsis being the most common infection type. The difference between the severity of sepsis between the two treatment arms was significant with greater severity in the combination arm; sepsis Grade 4+ was seen in 11 patients in the combination arm compared to 2 patients in azacitidine alone arm (Table 3). There were 17 deaths due to
Table 2. Molecular characteristics of cohort with baseline samples.
AZA (n=35)
LEN-AZA (n=31)
5 10
21
TOTAL (n=66)
8 24
42
Targeted Amplicon Sequencing TP53mut
TET2mut
High-risk molecular profile
(TP53mutand/orASXL1mut and/orRUNX1mut and/orEZH2mut) low-risk molecular profile
(SF3B1mut only)
SNP-Array
5q-
Monosomy 7/7q- 20q-
Trisomy 8
17p-
7qCNLOH
Combined molecular profile
TP53 abnormality (TP53mut and/or 17p-)
High-risk molecular profile 22 21
(TP53mut , ASXL1mut , RUNX1mut ,
EZH2mut , IPSS-RsnpP, IPSS-RsnpVP)
mut: mutated; LOH: loss of heterozygosity; IPSS-RsnpP or VP: IPSS-R SNP-A poor cytogenetic or very poor cytogenetic risk.
3 14
21
415
6612
639 448 06*6 246 4 2 4
358 43
Table 3. Non-hematologic toxicity; infections, grade 3 and above.
Infection type
Any Infection
GI/Abdo Renal/Urologic Respiratory
Sepsis overall Sepsis grade 3 Sepsis grade 4 Sepsis grade 5 Skin/Mucosal/Eye All other infections
AZA
LEN+AZA
N. patients
34 (43%)
6 (8%) 0 (0%) 9 (11%) 18 (23%) 16
2
0
9 (11%) 5 (6%)
No. episodes
62
7 0 10 29
11 5
N patients
34 (43%)
7 (9%)
2 (3%) 14 (18%) 19 (24%) 8
10
1
9 (11%) 6 (8%)
No. episodes
71
10 2 18 29
P=0.02
9 6
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