Risk of subsequent primary malignancies
in patients with multiple myeloma
before and after the introduction of novel therapies
Ola Landgren, M.D., Ph.D., Senior Investigator
Multiple Myeloma Section, National Cancer Institute, NIH
Paris, May 5, 2011
Disclosure
Conflicts of interest: None
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Background
· Increased frequency of myeloid malignancies
noted among myeloma patients since 1970s
· Although underlying biological mechanisms
are poorly understood, treatment-related
factors (e.g., melphalan) considered a main
source
Aims of this population-based study
· Define risk of primary hematologic and
solid malignancies subsequent to
myeloma, compared to general population
· For the first time, assess role of treatment
and non-treatment related factors
Mailankody et al., and Landgren (submitted)
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Methods patients and hospitals
· High-quality population-based data from
Sweden (1986-2005)
· All incident myeloma pts
· Nationwide MGUS cohort1
· Age- and gender-specific incidence rates
for entire population during study period
· Risks before/after 1995 (intro high-dose
melphalan/ASCT)
Mailankody et al., and Landgren (submitted); 1Landgren et al., Blood 2009
Results patients' characteristics
Variable
MyelomaMGUS
Total number, n (%)
8740 (100)
5652 (100)
<65 yrs at dx, n (%)
2495 (29)
1585 (28)
Male sex, n (%)
4811 (55)
2845 (50)
Year of dx
1986-1994, n (%)
4228 (48)
1362 (24)
1995-2005, n (%)
4512 (52)
4290 (76)
Follow-up data (cancer and mortality) available until end of 2006
Mailankody et al., and Landgren (submitted)
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Results risk of any malignancy
Myeloma
MGUS
Mailankody et al., and Landgren (submitted)
Results hematologic malignancies
Mailankody et al., and Landgren (submitted)
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Results MGUS and risk of AML/MDS,
by isotype and M-spike (g/dL)
Mailankody et al., and Landgren (submitted)
Results cumulative incidence
of AML/MDS
Mailankody et al., and Landgren (submitted)
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Results risk of AML/MDS following
myeloma, by calendar period
In myeloma patients*, AML/MDS risk was
very similar before/after 1995 (intro of high-
dose melphalan/ASCT)
Before 1995
SIR=33.34 (95%CI: 12.23-72.57)
1995 or later
SIR=23.19 (95%CI: 11.98-40.50)
*<65 years at diagnosis
Mailankody et al., and Landgren (submitted)
Results solid malignancies
Mailankody et al., and Landgren (submitted)
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Summary and conclusions (1 of 2)
· Our novel finding that MGUS
is associated with AML/MDS
risk supports a role for non-
treatment related factors
Summary and conclusions (2 of 2)
· AML/MDS risk similar before/
after intro of HDM-ASCT
suggests "high-dose and low-
dose melphalan = similar risk?"
· Longer follow-up needed to
better define secondary tumor
risks in the IMiD-era
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Proposed model for second
malignancies following myeloma
Thomas and Landgren (in manuscript)
Collaborators
Sham Mailankody1, MD
Lynn Goldin1, PhD
Ruth Pfeiffer1, PhD
Neha Korde1, MD
Sigurdur Kristinsson2, MD, PhD
Ingemar Turesson3, MD, PhD
Magnus Bjorkholm2, MD, PhD
Ola Landgren1, MD, PhD
1National Cancer Institute, NIH, Bethesda, Maryland, USA
2Karolinska Institute, Stockholm, Sweden
3Malmo University Hospital, Malmo, Sweden
www.multiplemyeloma.cancer.gov
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