Secondary malignancies in Myeloma:
an emerging issue?
Jean-Paul Fermand
Département d'Immunologie Clinique
Hôpital Saint Louis, Paris
Secondary malignancies in Myeloma
15:40 - 15:55 M. ATTAL (Fr.)
Maintenance treatment with lenalidomide after transplantation for myeloma:
analysis of secondary malignancies within the ifm 2005-02 trial
15:55 - 16:10 P.L. MCCARTHY JR (U.S.)
Phase III intergroup study of lenalidomide versus placebo maintenance therapy
following single autologous stem cell transplant for multiple myeloma:
calgb ecog bmt-ctn 100104
16:10 - 16:25 A. PALUMBO (It.)
Secondary malignancies in elderly myeloma patients
16:25 - 16:30 G.J. MORGAN (U.K.)
Retrospective analysis of the long term safety of lenalidomide
± dexamethasone in relapsed/refractory Myeloma patients
: analysis of pooled data and incidence rates of second primary malignancy
16:30 - 16:35 O. LANDGREN (U.S.A.)
Risk of subsequent primary malignancies in patients with multiple myeloma
before and after the introduction of novel therapies: a population-based study in sweden
1
Secondary malignancies in Myeloma
not an emerging issue, a come back
The Chemotherapy of Plasma-Cell Myeloma and the Incidence of Acute Leukemia
DE. Bergsagel, AJ. Bailey, GR. Langley, RN. MacDonald, DF. White and AB. Miller
N Engl J Med 1979; 301:743-748 October 4, 1979
Actuarial risk of developing
Group A
Group B
Group C
acute leukemia
sequential
alternating
concurrent
17% at 50 months
Melphalan
Melphalan Melphalan, Cytoxan &
Carmustine
Cytoxan
Carmustine
Failure or Relapse
Continue to death
R
Cytoxan
Carmustine
Secondary
New
malignancies
Malignancies Among
in
Cancer Myeloma
Survivors:
Surveillance Epidemiology & End Results (SEER) Cancer Registries, 1973-2000
GM Dores et al, National Cancer Institute, Bethesda, 2006
2
Secondary
New
malignancies
Malignancies Among
in
Cancer Myeloma
Survivors:
Surveillance Epidemiology & End Results (SEER) Cancer Registries, 1973-2000
Risk of subsequent cancers after Myeloma
Observed
Expected
Exp./Obs. Exces absolute risk per
(O)
(E)
(O/E) 10,000 person-yrs (EAR)
< 70 yrs of age
674
624,11
1,08
10,88
70 yrs of age
545
631,73
0,86
-34,41
male
460
468,83
0,98
-2,58
female
759
787,02
0,96
-7,60
GM Dores et al, National Cancer Institute, Bethesda, 2006
Secondary
New
malignancies
Malignancies Among
in
Cancer Myeloma
Survivors:
Surveillance Epidemiology & End Results (SEER) Cancer Registries, 1973-2000
Risk of subsequent cancers after Myeloma
GM Dores et al, National Cancer Institute, Bethesda, 2006
3
Secondary
New
malignancies
Malignancies Among
in
Cancer Myeloma
Survivors:
Surveillance Epidemiology & End Results (SEER) Cancer Registries, 1973-2000
Risk of subsequent cancers after Myeloma
GM Dores et al, National Cancer Institute, Bethesda, 2006
Secondary
Increased frequency malignancies
using the new in Myeloma
anti-myeloma agents,
particularly the Imids?
3 randomized placebo-controlled trials
Secondary
Overall survival
malignancies
(not only progression
(and other treatment-
free survival)
related adverse effects)
4
Secondary malignancies in Myeloma: why?
linked to some mechanisms of action of Imids?
Selection
Chronic
pressure
Pre-existing
stimulation
tumor cell
Mutagen
stimulation
effect
Different mechanisms depending on
tumor type?
Secondary malignancies
Risk factors?
in
- Myeloma:
patient or
why?
disease related
- treatment related (duration)
Preventive effect of steroids?
Immune
surveillance/
Impaired post-
anti-tumor
chemo immune
reconstitution
immunity failure
5
Secondary malignancies in Myeloma
Conclusions
Epidemiological studies
Molecular
characterization of
secondary tumors
Experimental models
Thank you for your attention
6
Secondary malignancies in Myeloma
15:40 - 15:55 M. ATTAL (Fr.)
Maintenance treatment with lenalidomide after transplantation for myeloma:
analysis of secondary malignancies within the ifm 2005-02 trial
15:55 - 16:10 P.L. MCCARTHY JR (U.S.)
Phase III intergroup study of lenalidomide versus placebo maintenance therapy
following single autologous stem cell transplant for multiple myeloma:
calgb ecog bmt-ctn 100104
16:10 - 16:25 A. PALUMBO (It.)
Secondary malignancies in elderly myeloma patients
16:25 - 16:30 G.J. MORGAN (U.K.)
Retrospective analysis of the long term safety of lenalidomide
± dexamethasone in relapsed/refractory Myeloma patients
: analysis of pooled data and incidence rates of second primary malignancy
16:30 - 16:35 O. LANDGREN (U.S.A.)
Risk of subsequent primary malignancies in patients with multiple myeloma
before and after the introduction of novel therapies: a population-based study in Sweden
7