Published by the C
International I
Myel
T
oma Founda
ItionN
Special
G
Edition: ASCO 2007 S
Q2/2007
ThalidomideandRevlimid®Issue
The International Myeloma Foundation (IMF) presents this special edition of CITINGS, our
premiere publication featuring the most up-to-date information on myeloma treatment, focused on thalidomide
and Revlimid. This special edition corresponds with the 43rd annual meeting of American Society of
Clinical Oncology (ASCO). In this CITINGS, we have highlighted selected thalidomide and Revlimid data
presentations from the ASCO meeting. We also provide references to the latest published journal articles on both
thalidomide and Revlimid from the second quarter of this year.
It is our hope that CITINGS will help keep you abreast of the latest developments in myeloma treatment.
As always, we welcome your feedback; you may contact the IMF at (800) 452-CURE (2873) or at our website
www.myeloma.org.
Susie Novis, President, IMF
AmericanSocietyofClinicalOncology
Presentations2007
Saturday, June 2, 2007
An analysis of erythropoietin (EPO) and venous thromboembolic events (VTE) in multiple myeloma
(MM) patients (pts) treated with anthracycline-based chemotherapy and the immunomodulator agent
thalidomide.
Presenter: Rachid C Baz, MD
Time: 8:00 AM - 12:00 PM
Location: S Hall A2
Abstract No: 8107
Poster Number: CC1
General Poster Sessions: Lymphoma and Plasma Cell Disorders
Inhibition of cell proliferation by lenalidomide is associated with stimulation of Egr1 transcriptional
activity in a chromosome 5 deleted Burkitt's lymphoma and multiple myeloma cell line.
Presenter: Anita K Gandhi, PhD
Time: 8:00 AM - 12:00 PM
Location: S Hall A2
Abstract No: 8110
Poster Number: CC4
General Poster Sessions: Lymphoma and Plasma Cell Disorders
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Funded by an educational grant from Celgene Corporation.
A systematic review of the incidence of venous thromboembolism (VTE) and effectiveness of
prophylaxis in patients with multiple myeloma (MM) receiving thalidomide.
Presenter: Cynthia M Wu, MD
Time: 2:00 PM - 6:00 PM
Location: S Hall A2
Abstract No: 9056
Poster Number: BB3
General Poster Sessions: Patient and Survivor Care
Sunday, June 3, 2007
Long-term responses to thalidomide and rituximab in Waldenstrom's macroglobulinemia.
Presenter: Jacob Drobnyk Soumerai
Time: 1:00 PM - 1:15 PM
Location: E354b
Abstract No: 8017
Oral Abstract Presentation Sessions: Myeloma
Impact of prior thalidomide (T) therapy on the efficacy of pegylated liposomal doxorubicin (PLD) and
bortezomib (B) in relapsed/refractory multiple myeloma (RRMM).
Presenter: Pieter Sonneveld, MD
Time: 3:00 PM - 3:15 PM
Location: E354b
Abstract No: 8023
Oral Abstract Presentation Sessions: Myeloma
Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose
dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern
Cooperative Oncology Group
Presenter: S. V Rajkumar, MD
Time: 3:30 PM - 3:45 PM
Location: E354b
Abstract No: LBA8025
Oral Abstract Presentation Sessions: Myeloma
Monday, June 4, 2007
Comparison of melphalan-prednisone-thalidomide (MP-T) to melphalan-prednisone (MP) in
patients 75 years of age or older with untreated multiple myeloma (MM). Preliminary results of the
randomized, double-blind, placebo controlled IFM 01-01 trial.
Presenter: Dr. Cyrille Hulin
Time: 7:30 AM - 7:45 AM
Location: E Arie Crown Theater
Abstract No: 8001
Clinical Science Symposium: How New Agents Work in Multiple Myeloma
Factors predictive of outcome in relapsed, refractory multiple myeloma patients treated with
bortezomib, melphalan, prednisone, and thalidomide (VMPT).
Presenter: Antonio Palumbo, MD
Time: 2:00 PM - 6:00 PM
Location: E451a
Time: 5:00 PM - 6:00 PM
Location: E354b
Abstract No: 8048
Poster Number: 23
Poster Discussion Sessions: Lymphoma and Plasma Cell Disorders
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Thalidomide/RevlimidPublications2ndQuarter,2007
NEmerging drugs in multiple myeloma.
Ghobrial IM, Leleu X, Hatjiharissi E, Hideshima T, Mitsiades C, Schlossman R, Anderson KC, Richardson P.
Expert Opin Emerg Drugs. 2007 Mar;12(1):155-63.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17355220&query_
hl=1&itool=pubmed_DocSum
This review summarizes the role of novel therapeutic agents, including thalidomide and lenalidomide, in multiple myeloma.
The treatment of multiple myeloma has seen significant changes from the time of the initial use of cytotoxic agents such as
melphalan, to the introduction of high-dose chemotherapy and stem cell transplantation, and most recently the era of novel
targeted agents. These new drugs have rapidly become the mainstay of therapy of this disease and transformed the treatment
paradigm, leading to improvements in survival and quality of life. Existing therapeutic options include agents such as
thalidomide, bortezomib and lenalidomide, either used alone or in combination with standard agents, including glucocorticoids,
and in conjunction with high-dose chemotherapy supported with stem cell transplantation. Several other targeted agents have
demonstrated exciting preclinical activity, and are presently being tested in early Phase I and II clinical trials. This review
summarizes the role of novel therapeutic agents in multiple myeloma, and the promising effect of multiple new agents in
development.
NLenalidomide: immunomodulatory, antiangiogenic, and clinical activity in solid tumors.
Dreicer R.
Curr Oncol Rep. 2007 Mar;9(2):120-3.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17288877&query_
hl=1&itool=pubmed_DocSum
The author discusses lenalidomide as an agent in solid tumors.
Lenalidomide is a novel analog of thalidomide with both immunomodulatory and antiangiogenic properties that are more
potent than those same properties in the parent compound. Work in several antiangiogenic model systems has provided early
evidence of potential mechanisms of its clinical activity. Recent US Food and Drug Administration approval of lenalidomide
for patients with deletion 5q myelodysplastic syndromes and advanced multiple myeloma has provided impetus for further
evaluation of this agent in solid tumors.
NMultiple myeloma therapies.
Strobeck M.
Nat Rev Drug Discov. 2007 Mar;6(3):181-2.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17396289&query_
hl=5&itool=pubmed_DocSum
No abstract available.
NTargeted therapeutics for multiple myeloma: The arrival of a risk-stratified approach.
Fonseca R, Stewart AK.
Mol Cancer Ther. 2007 Mar;6(3):802-10.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17363477&query_
hl=1&itool=pubmed_DocSum
The authors discuss the use of novel drugs, including thalidomide and lenalidomide, in combination, as myeloma treatment
becomes increasingly personalized and guided by genetic testing and prognostic factors.
Multiple myeloma (MM) remains an incurable hematologic malignancy characterized by frequent early responses, inevitably
followed by treatment relapse. Until recently, few effective therapies existed. Indeed, the use of alkylating agents and
corticosteroids had remained the treatment of choice for almost four decades. Several novel agents for MM have now become
available, including the immunomodulatory drugs thalidomide and lenalidomide, as well as the proteasome inhibitor
bortezomib. Each of these agents is undergoing extensive clinical evaluation in combination with other therapies to produce
unprecedented response rates in newly diagnosed and relapsed MM. Nevertheless, relapse remains universal and further
therapeutics with broad activity are required. Importantly, it has become clear that pivotal genetic events are the primary
harbingers of clinical outcome and novel targeted therapy approaches using existing approved drugs or novel agents, which
address that disrupted signaling pathways are now in various stages of clinical testing. It seems increasingly likely that novel
drug combinations, which together turn off these critical Achilles heels, will become the standard of care and that treatment will
become increasingly personalized and guided by genetic testing and prognostic factors.
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NMaintenance therapy in multiple myeloma.
Mihelic R, Kaufman JL, Lonial S.
Leukemia. 2007 Mar 8; [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17344913&query_
hl=1&itool=pubmed_DocSum
The authors discuss the current and future use of novel agents, including thalidomide and lenalidomide, for myeloma
"maintenance" therapy.
Therapeutic advances in the treatment of multiple myeloma have significantly improved remission duration and overall survival
(OS). These strategies have included the use of immunotherapy (interferon), novel agents (bortezomib, thalidomide, and
lenalidomide), corticosteroids, and chemotherapy. While novel agents have had a major impact on response rates with initial
therapy, most patients with multiple myeloma will eventually relapse. In the setting of minimal residual disease following
standard dose or high-dose therapy, a number of different `maintenance' strategies have emerged to prolong the duration of initial
or subsequent remissions. The impact of these strategies on OS and event-free survival (EFS) is critically important, as the use
of ineffective maintenance therapy adds the burden of additional cost, morbidity, and may reduce quality of life. Truly successful
maintenance therapy will be effective in the setting of minimal residual disease, and will improve not only EFS, but also OS. This
review summarizes the currently available data in the maintenance setting for multiple myeloma, and will discuss potential future
trials to further address this important issue.
NResveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-
regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products
in human multiple myeloma cells.
Bhardwaj A, Sethi G, Vadhan-Raj S, Bueso-Ramos C, Takada Y, Gaur U, Nair AS, Shishodia S, Aggarwal BB.
Blood. 2007 Mar 15;109(6):2293-302. [Epub 2006 Dec 12.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17164350&query_
hl=1&itool=pubmed_DocSum
The authors investigate whether resveratrol could suppress the proliferation of multiple myeloma cells and conclude that their
findings suggest that resveratrol may have potential in its treatment, including potentiating the apoptotic effects of thalidomide.
Whether resveratrol, a component of red grapes, berries, and peanuts, could suppress the proliferation of multiple myeloma
(MM) cells by interfering with NF-kappaB and STAT3 pathways, was investigated. Resveratrol inhibited the proliferation of
human multiple myeloma cell lines regardless of whether they were sensitive or resistant to the conventional chemotherapy
agents. This stilbene also potentiated the apoptotic effects of bortezomib and thalidomide. Resveratrol induced apoptosis as
indicated by accumulation of sub-G(1) population, increase in Bax release, and activation of caspase-3. This correlated with
down-regulation of various proliferative and antiapoptotic gene products, including cyclin D1, cIAP-2, XIAP, survivin, Bcl-
2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT. These effects of
resveratrol are mediated through suppression of constitutively active NF-kappaB through inhibition of IkappaBalpha kinase
and the phosphorylation of IkappaBalpha and of p65. Resveratrol inhibited both the constitutive and the interleukin 6-induced
activation of STAT3. When we examined CD138(+) plasma cells from patients with MM, resveratrol inhibited constitutive
activation of both NF-kappaB and STAT3, leading to down-regulation of cell proliferation and potentiation of apoptosis induced
by bortezomib and thalidomide. These mechanistic findings suggest that resveratrol may have a potential in the treatment of
multiple myeloma.
NLenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an
effective and tolerated regimen for myeloma patients.
Morgan GJ, Schey SA, Wu P, Srikanth M, Phekoo KJ, Jenner M, Davies FE.
Br J Haematol. 2007 May;137(3):268-9.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17408469&query_
hl=3&itool=pubmed_DocSum
No abstract available.
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NThalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral
blood stem cell collection yield.
Breitkreutz I, Lokhorst HM, Raab MS, Holt BV, Cremer FW, Herrmann D, Glasmacher A, Schmidt-Wolf IG, Blau IW, Martin H,
Salwender H, Haenel A, Sonneveld P, Goldschmidt H.
Leukemia. 2007 Mar 22; [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17377586&query_
hl=1&itool=pubmed_DocSum
The authors conduce a phase III study investigating the influence of thalidomide on the outcome of peripheral blood stem
cell (PBSC) collection in multiple myeloma before peripheral autologous blood stem cell transplantation. They conclude that
thalidomide as part of induction regimen is associated with better response rates but significantly affects the yield of PBSC
collection.
In a phase III randomized, multicenter study, the German-speaking Myeloma-Multicenter Group (GMMG) and the Dutch-
Belgian Hemato-Oncology Cooperative Group (HOVON) group investigated the influence of thalidomide (Thal) on the
outcome of peripheral blood stem cell (PBSC) collection in multiple myeloma (MM) before peripheral autologous blood stem
cell transplantation (ABSCT). We analyzed the data of 398 myeloma patients after induction with Thal, doxorubicin and
dexamethasone (TAD) in comparison with vincristine, doxorubicin and dexamethasone (VAD) followed by mobilization with
cyclophosphamide, doxorubicin, dexamethasone (CAD) and PBSC collection. Within both the study groups, patients treated
with TAD showed to collect significantly fewer CD34(+) cells compared with VAD (GMMG, TAD: median 9.8 x 10(6)/kg;
range 2.0-33.6; VAD: median 10.9 x 10(6)/kg range 3.0-36.0; P=0.02) (HOVON, TAD: median 7.4 x 10(6)/kg; range 2.0-
33.0; VAD: median 9.4 x 10(6)/kg; range 0.0-48.7; P=0.009). However, engraftment after peripheral autologous stem cell
transplantation showed no difference between Thal and VAD groups. We conclude that Thal as a part of induction regimen is
associated with better response rates (GMMG-HD3: CR/PR 79%, VAD: CR/PR 58%; HOVON-50: TAD: CR/PR 81%, VAD:
CR/PR 61%), but significantly affects the yield of PBSC collection. Nevertheless, the number of total CD34(+) cells collected
was sufficient for double autologous transplantation in 82% of the Thal patients, with at least 2.5 x 10(6)/kg CD34(+) cells.
NCurrent therapies for multiple myeloma.
Tariman JD.
J Infus Nurs. 2007 Mar-Apr;30(2):113-8; quiz 121.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17413496&query_
hl=5&itool=pubmed_DocSum
This article overviews multiple myeloma and its current therapies, with emphasis on bortezomib and lenalidomide.
Multiple myeloma is an incurable B-cell malignancy of plasma cells but also a highly treatable disease. This article is an overview
of multiple myeloma and its current therapies, with emphasis on bortezomib and lenalidomide. Important nursing considerations
related to the management of common adverse events are also described.
NAssessing response rates in clinical trials of treatment for relapsed or refractory multiple myeloma: a
study of bortezomib and thalidomide.
Prince HM, Schenkel B, Mileshkin L.
Leukemia. 2007 Apr;21(4):818-20. [Epub 2007 Feb 15.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17301817&query_
hl=1&itool=pubmed_DocSum
No abstract available.
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NAssessing response rates in clinical trials of treatment for relapsed or refractory multiple myeloma: a
study of bortezomib and thalidomide by H Prince, Brad Schenkel and Linda Mileshkin.
Durie BG, Rajkumar SV.
Leukemia. 2007 Apr;21(4):821. [Epub 2007 Feb 15.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17301816&query_
hl=1&itool=pubmed_DocSum
No abstract available.
NPulsed cyclophosphamide, thalidomide and dexamethasone regimen for previously treated patients with
multiple myeloma: Long term follow up and disease control after subsequent treatments.
Roussou M, Anagnostopoulos A, Kastritis E, Matsouka C, Barmparousi D, Koutsoukou V, Dimopoulos MA.
Leuk Lymphoma. 2007 Apr;48(4):754-8.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17454634&query_
hl=1&itool=pubmed_DocSum
The authors reassess their original series of 43 patients with previously treated multiple myeloma who had received a pulsed
cyclophosphamide, thalidomide, dexamethasone (CTD) regimen. They conclude that some patients enjoy long responses after
CTD and that several patients who progressed after CTS may respond to treatment with a novel agent-based regimen.
There are limited data regarding the long term follow up after thalidomide based regimen and the outcome of patients when
they progress and they receive further treatment. We reassessed our original series of 43 patients with previously treated multiple
myeloma who had received a pulsed cyclophosphamide, thalidomide, dexamethasone (CTD) regimen. Among the 43 patients,
14 did not respond to pulsed CTD and 29 (67%) achieved at least a partial response. The median PFS for all patients was 10
months. After a median follow up of 24 months (range 1 - 62), the 3 year PFS is 14% and 3 patients remain off treatment and
without progression for 55+, 55+ and 56+ months respectively. Moreover, 28% of patients who progressed after CTD achieved
a partial response after subsequent treatment which included thalidomide, bortezomib or lenalidomide. The median PFS of
these patients was 5 months and the 1 year PFS was 20%. Furthermore, 31% of patients who had responded to CTD and then
progressed (CTD sensitive) responded to subsequent treatment. We conclude that some patients enjoy long responses after CTD
and that several patients who progress after CTD may respond to treatment with a novel agent-based regimen.
NTargeted therapy of multiple myeloma based upon tumor-microenvironmental interactions.
Anderson KC.
Exp Hematol. 2007 Apr;35(4 Suppl 1):155-62.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17379101&query_
hl=15&itool=pubmed_DocSum
The author discusses the recent advances in genomics and proteomics that has allowed for the establishment of a new myeloma
treatment paradigm, including the ability of thalidomide and lenalidomide to overcome conventional drug resistance.
Multiple myeloma (MM) remains incurable, but recent advances in genomics and proteomics have allowed for advances in our
understanding of disease pathogenesis, identified novel therapeutic targets, allowed for molecular classification, and provided the
scientific rationale for combining targeted therapies to increase tumor cell cytotoxicity and abrogate drug resistance. Besides these
advances, recognition of the role of the bone marrow (BM) milieu in conferring growth, survival, and drug resistance in MM
cells, both in laboratory and animal models, has allowed for the establishment of a new treatment paradigm targeting the tumor
cell and its microenvironment to overcome drug resistance and improve patient outcomes in MM. In particular, thalidomide,
bortezomib, and lenalidomide all overcome conventional drug resistance, not only by directly inducing tumor cell cytotoxicity,
but by inhibiting adhesion of MM cells to BM. This abrogates constitutive and MM-binding-induced transcription and secretion
of cytokines, inhibits angiogenesis, and augments host anti-MM immunity. These three drugs have rapidly translated from
bench to bedside and in treatment protocols of MM, first in patients with relapsed refractory disease, and then alone and in
combination in newly diagnosed patients. Promising novel targeted agents include the novel proteasome inhibitor NPI-0052 and
the heat shock protein inhibitor KOS-953. Importantly, gene-array, proteomic, and cell-signaling studies have not only helped to
identify in vivo mechanisms of action and drug resistance to novel agents, but also aided in the design of promising combination-
therapy protocols.
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NThalidomide-dexamethasone plus pegylated liposomal doxorubicin vs. thalidomide-dexamethasone: a
case-matched study in advanced multiple myeloma.
Offidani M, Bringhen S, Corvatta L, Falco P, Marconi M, Avonto I, Piersantelli MN, Polloni C, Boccadoro M, Leoni P, Palumbo A.
Eur J Haematol. 2007 Apr;78(4):297-302. [Epub 2007 Feb 5.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17286608&query_
hl=1&itool=pubmed_DocSum
The authors perform a case-matched study comparing patients with relapsed/refractory multiple myeloma receiving thalidomide-
dexamethasone alone (Thal-Dex) and the combination thalidomide-dexamethasone-liposomal peg ylated doxorubicin (ThaDD)
and find ThaDD to have significantly higher response rates with no significantly added side effects.
Objectives: Nearly all patients with multiple myeloma (MM) relapse or become refractory to front-line therapy. Several salvage
therapies have been explored, but the optimal combination regimen has not been defined. We performed a case-matched
study comparing patients with relapsed/refractory MM receiving thalidomide-dexamethasone alone or the combination
thalidomide-dexamethasone-liposomal pegylated doxorubicin. Methods: Forty-seven patients received thalidomide (100 mg/
d), dexamethasone (40 mg p.o. on days 1-4 and 9-12), and pegylated liposomal doxorubicin (40 mg/m(2) on day 1 every 28
d) (ThaDD). Their clinical outcome was compared with that of 47 pair mates selected from patients treated at relapse with
thalidomide (100 mg/d) and dexamethasone (40 mg p.o. on days 1-4) (Thal-Dex) and matched for age, beta2-microglobulin
and previous therapy. Results and conclusions: Overall response rate was significantly higher in ThaDD group (92% vs. 63.5%;
P < 0.0001) as partial response rate (>/=PR) (75.5% vs. 59.5%; P = 0.077), very good partial response rate (>/=VGPR) (36% vs.
15%; P = 0.018) and near complete remission rate (>/=nCR) (30% vs. 10.5%; P = 0.002). Non-hematologic toxicity was similar
in the two groups of patients whereas hematologic toxicity and infections were significantly higher in ThaDD patients. Median
progression-free survival, event-free survival, and overall survival were significantly longer in patients receiving ThaDD than in
those treated with Thal-Dex. ThaDD regimen significantly improved response rate and overall survival in comparison with Thal-
Dex. Although the frequency of hematologic toxicity and infections resulted higher in ThaDD group compared with control
group, they were not particularly frequent after adequate prophylaxis was added and were easily managed when occurred.
NPatterns of Survival in Multiple Myeloma: A Population-Based Study of Patients Diagnosed in Sweden
From 1973 to 2003.
Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm M.
J Clin Oncol. 2007 Apr 9; [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17420512&query_
hl=1&itool=pubmed_DocSum
The authors define patterns of survival among all multiple myeloma (MM) patients diagnosed in Sweden during a 30-year period.
They find that one-year MM survival has increased for all age groups during the last decades; 5-year and 10-year MM survival has
increased in younger patients (younger than 60 to 70 years). They conclude that high-dose melphalan with subsequent autologous
stem-cell transplantation, thalidomide, and a continuous improvement in supportive care measures are probably the most
important factors contributing to these findings.
PURPOSE: To define patterns of survival among all multiple myeloma (MM) patients diagnosed in Sweden during a 30-year
period.
PATIENTS AND METHODS: A total of 14,381 MM patients (7,643 males; 6,738 females) were diagnosed in Sweden from
1973 to 2003 (median age, 69.9 years; range 19 to 101 years). Patients were categorized into six age categories and four calendar
periods (1973 to 1979, 1980 to 1986, 1987 to 1993, and 1994 to 2003). We computed relative survival ratios (RSRs) as
measures of patient survival.
RESULTS: One-year survival improved (P < .001) over time in all age groups and RSRs were 0.73, 0.78, 0.80, and 0.82 for
the four calendar periods; however, improvement in 5-year (P < .001) and 10-year (P < .001) RSR was restricted to patients
younger than 70 years and younger than 60 years, respectively. For the first time, in analyses restricted to MM patients diagnosed
at age younger than 60 years, we found a 29% (P < .001) reduced 10-year mortality in the last calendar period (1994 to 2003)
compared with the preceding calendar period (1987 to 1993). Females with MM had a 3% (P = .024) lower excess mortality
than males.
CONCLUSION: One-year MM survival has increased for all age groups during the last decades; 5-year and 10-year MM
survival has increased in younger patients (younger than 60 to 70 years). High-dose melphalan with subsequent autologous stem-
cell transplantation, thalidomide, and a continuous improvement in supportive care measures are probably the most important
factors contributing to this finding. New effective agents with a more favorable toxicity profile are needed to improve survival
further, particularly in the elderly.
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