2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Trial
Author and Year
An unexpected finding from the three lenalidomide maintenance
trials was an increase in the incidence of secondary
cancers (SPMs), including hematological malignancies and
solid tumors; nearly 8% in both post-ASCT studies compared
with 2% in the placebo groups. The difference compared with
Table 3. Toxical Patterns of Maintenance Trials
Adverse Events* (%)
*All Grade Unless Specified
Discontinuation of
Treatment due to Drug-Related
Adverse Events (%)
Median Duration of
Treatment and Median
Received Dose
Thalidomide Maintenance
Post ASCT
IFM 95–02 Neuropathy (68%), fatigue (34%), constipation (20%), neutropenia
(7%)
39% 15 mo (0.1–50)
Attal et al 2006 NB: grade 3/4 neuropathy (7%), infection (6%) (mainly related to neuropathy) 200 mg/d
Total therapy 2 �grade2 neuropathy (15%), thrombosis (6%) N/A 80% stopped thalidomide
Barlogie et al 2006–2008
within 2 yr
ALLG MM6 Neuropathy (52%), infection 23%, fatigue (14%), constipation (18%) 30% 58% still on therapy at 12 mo
Spencer et al 2009 NB: grade 3/4 neuropathy (10%) (mainly related to neuropathy) 100 mg/d
HOVON-50 Neuropathy (64%) 33% 2 yr
Lokhorst et al 2010 (mainly related to neuropathy)
NCIC CTG MY.10
Stewart et al 2010
Post ASCT or Chemotherapy
Grade 3/4 neuropathy (10%), thrombosis (7%), fatigue (7%) 16 mo
MRC myeloma IX N/A 52% 7 mo (0–50)
Morgan et al 2012
Post Chemotherapy
(mainly related to neuropathy) 50 mg/d
GIMEMA 55% AE grade 3/4 N/A 8 mo (0.03–39.40)
Palumbo et al 2008 within the entire program
HOVON 49
Wijermans et al 2010
�grade 2 neuropathy (54%) N/A 8.4 mo (1.4–35.9)
NMSG Grade 3–4 non-hematological AE (40%, neuropathy (6%), thrombosis 56% at 1 yr (mainly related to 7,5 mo
Waage et al 2010 (8%)
neuropathy)
CEMSG Leucopenia (59%), fatigue (78%), neurological (69%), infection (28%),
23% 13 mo
Ludwig et al 2010
Post ASCT
constipation (44%), skin (33%)
Lenalidomide Maintenance
75 mg/d
IFM 2005–02 Neutropenia (68%), febrile neutropenia (2%), thrombocytopenia
(24%), diarrhea (40%), fatigue (47%), upper respiratory infection
(70%), neuropathy (23%), skin rash (20%), cramps (39%)
25% at time of unblinding N/A
Attal et al 2011 SPMs n � 26
CALBG 100104 Grade 3/4 Neutropenia (43%), febrile neutropenia (6%),
thrombocytopenia (13%), diarrhea (4%), fatigue (5%), infection
(33%), skin rash (4%)
12% N/A
McCarthy et al 2011
Post Chemotherapy
SPMs n � 15
MM 015 Grade 4 hematologic AEs: thrombocytopenia (5%), neutropenia (4%),
5% N/A
Palumbo et al 2011
Post ASCT
anemia (3%); Grade 3/4 nonhematologic AEs: bone pain (5%),
diarrhea (5%) SPMs 8%
Bortezomib Maintenance
HOVON 65/HD4 Grade 2/4 neuropathy (23%), GI symptoms (23%), infections (53%) 9% 49% during 2 yr
Sonneveld et al 2010 (mainly related to neuropathy)
PETHEMA/GEM Grade 1/3 neuropathy (12.2%) 15.6% N/A
Rosinol et al 2011
Post Chemotherapy
(mainly related to neuropathy)
GIMEMA Grade 3/4 neutropenia (38%), thrombocytopenia (22%), N/A N/A
Palumbo et al 2010 Infections (13%), neuropathy (8%), fatigue (6%), DVT (5%, Rash (4%)
GEM2005MAS65 VT: grade 3/4 neuropathy (9%), GI symptoms (4%), neutropenia (4%) VT 13% 20 mo (1–36)
Mateos et al 2011 VP 9% (mainly related to neuropathy)
Abbreviation: N/A, not available.
520
ATTAL AND ROUSSEL
placebo was statistically significant (p � 0.001), mainly after
24 months of treatment.
Intense investigation regarding the risk of SPMs in recipients
of lenalidomide has ensued. In addition to a suspected
intrinsic risk of second cancers in this disease, antimyeloma