Published by the C
International I
Myel
T
oma Founda
ItionNVOLG
UME III, ISSUE I S
Q1/2006
ThalidomideandRevlimidTMIssue
The International Myeloma Foundation (IMF) is pleased to present our first edition of
CITINGS for 2006. This quarterly publication features citations to the most up-to-date studies
on myeloma treatment. In this issue, we focus on thalidomide and RevlimidTM for the treatment
of multiple myeloma. Inside you will find references to the latest published journal articles on
both thalidomide and Revlimid from the first 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
or www.myeloma.org.
Susie Novis, President, IMF
Thalidomide/RevlimidTMPublications
JanuaryMarch,2006
NDoxorubicin and dexamethasone followed by thalidomide and dexamethasone is an
effective well tolerated initial therapy for multiple myeloma.
Hassoun H, Reich L, Klimek VM, Dhodapkar M, Cohen A, Kewalramani T, Zimman R, Drake L,
Riedel ER, Hedvat CV, Teruya-Feldstein J, Filippa DA, Fleisher M, Nimer SD, Comenzo RL.
Br J Haematol. 2006 Jan;132(2):155-61.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16398649&query_hl=1&itool=pubmed_DocSum
This study found that doxorubicin and dexamethasone for 2 or 3 months followed by thalidomide
and dexamethasone for 2 months (AD-TD regimen) administered with low-dose aspirin for deep
vein thrombosis prophylaxis was well tolerated and yielded a high response rate with minimal
treatment-related morbidity for patients with multiple myeloma (MM).
www.myeloma.org
(800) 452 - CURE (2873)
Funded by an educational grant from Celgene Corporation.
NImmunomodulatory analogues of thalidomide in the treatment of multiple myeloma.
Suppiah R, Srkalovic JG, Hussein MA.
Clin Lymphoma Myeloma. 2006 Jan;6(4):301-5.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16507207&query_hl=1&itool=pubmed_docsum
The clinical trial development of second-generation immunomodulatory drugs lenalidomide
(Revlimid) and CC-4047 (Actimid) are reviewed in this article. The authors state that both agents
demonstrate potent activity with manageable toxicities and provide another treatment opportunity
for patients with MM.
NIntravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple
myeloma.
Palumbo A, Avonto I, Bruno B, Ambrosini MT, Bringhen S, Cavallo F, Falco P, Boccadoro M.
Eur J Haematol. 2006 Jan 23; [Epub ahead of print].
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16438704&query_hl=1&itool=pubmed_docsum
The authors discuss the significant anti-myeloma activity of thalidomide combined with
conventional chemotherapies, including oral melphalan. Feasibility and efficacy of a three-drug
combination consisting of intravenous (i.v.) melphalan, prednisone, and thalidomide [M(i.v.)PT]
was evaluated in advanced myeloma patients.
NLow-dose thalidomide with pegylated liposomal doxorubicin and high-dose
dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter,
phase II study.
Offidani M, Corvatta L, Marconi M, Visani G, Alesiani F, Brunori M, Galieni P, Catarini M,
Burattini M, Centurioni R, Rupoli S, Scortechini AR, Giuliodori L, Candela M, Capelli D,
Montanari M, Olivieri A, Piersantelli MN, Leoni P.
Haematologica. 2006 Jan;91(1):133-6.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16434383&query_hl=1&itool=pubmed_docsum
The aim of this prospective, multicenter, phase II study was to investigate the combination of
pegylated liposomal doxorubicin (Caelyx) 40 mg/m2 on day 1 every 28 days, dexamethasone
40 mg p.o. on days 1-4 and 9-12, and thalidomide 100 mg daily in 50 patients with advanced
multiple myeloma.
www.myeloma.org
(800) 452 - CURE (2873)
NLow-dose Velcade, thalidomide and dexamethasone (LD-VTD): an effective regimen for
relapsed and refractory multiple myeloma patients.
Ciolli S, Leoni F, Gigli F, Rigacci L, Bosi A.
Leuk Lymphoma. 2006 Jan;47(1):171-3.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16321846&query_hl=1&itool=pubmed_DocSum
The study found that the LD-VTD regimen applied appears feasible and effective in elderly and
heavily pre-treated relapsed and refractory MM patients.
NNovel treatment approaches for patients with multiple myeloma.
Sinha R, Kaufman JL, Lonial S.
Clin Lymphoma Myeloma. 2006 Jan;6(4):281-8.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16507205&query_hl=1&itool=pubmed_docsum
The authors discuss the discovery of key signaling pathways needed for myeloma cell growth and
proliferation and the resultant plethora of new and different treatment options. Chief among these
new agents are the proteasome inhibitor bortezomib and the immunomodulatory agents
thalidomide and lenalidomide.
NThalidomide and dexamethasone: a new standard of care for initial therapy in multiple
myeloma.
Richardson P, Anderson K.
J Clin Oncol. 2006 Jan 20;24(3):334-6. Epub 2005 Dec 19.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16365174&query_hl=1&itool=pubmed_DocSum
Editorial.
NTreatment of multiple myeloma. [Article in French].
Terriou L, Leleu X, Yakoub-Agha I.
Bulletin du Cancer. 2006 Jan 1;93(1):101-6.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16455512&query_hl=1&itool=pubmed_docsum
This article examines the impact of thalidomide and its derivatives and Velcade on the history of
multiple myeloma.
www.myeloma.org
(800) 452 - CURE (2873)
NPhase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone
alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern
Cooperative Oncology Group.
Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR; Eastern Cooperative Oncology Group.
J Clin Oncol. 2006 Jan 20;24(3):431-6. Epub 2005 Dec 19.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16365178&query_hl=1&itool=pubmed_DocSum
This study found that thalidomide plus dexamethasone demonstrates significantly superior response
rates in newly diagnosed myeloma compared with dexamethasone alone. However, this must be
balanced against the greater toxicity seen with the combination.
NCurrent therapeutic uses of lenalidomide in multiple myeloma.
Hideshima T, Richardson PG, Anderson KC.
Expert Opin Investig Drugs. 2006 Feb;15(2):171-9.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16433596&query_hl=1&itool=pubmed_docsum
The researchers discuss the varying avenues of research into the molecular mechanisms of
antitumour activity of lenalidomide. They conclude that lenalidomide represents a new class of
antitumour agents that is useful in the treatment of MM.
NPrimary treatment with pulsed melphalan, dexamethasone and thalidomide for elderly
symptomatic patients with multiple myeloma.
Dimopoulos MA, Anagnostopoulos A, Terpos E, Repoussis P, Zomas A, Katodritou E, Kyrtsonis
MC, Delibasi S, Vassou A, Pouli A, Zervas K, Anagnostopoulos N, Maniatis A; Greek Myeloma
Study Group.
Haematologica. 2006 Feb;91(2):252-4.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16461313&query_hl=1&itool=pubmed_docsum
The researchers report on fifty patients with MM who received primary treatment with melphalan,
dexamethasone and thalidomide. Sixty-two percent of patients achieved a partial response and 10%
a complete response. The median time to response was 2 months.
NRole of lenalidomide in the treatment of multiple myeloma and myelodysplastic syndrome.
Maier SK, Hammond JM.
Ann Pharmacother. 2006 Feb;40(2):286-9. Epub 2006 Jan 10.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16403850&query_hl=1&itool=pubmed_DocSum
The authors conclude that lenalidomide is a potent immunomodulating drug that offers different
mechanisms of action and therapeutic potential for the treatment of MM, MDS, and other
malignancies.
www.myeloma.org
(800) 452 - CURE (2873)
NShould we screen patients for inherited thrombophilia before starting thalidomide?
Otrock ZK, Mahfouz RA, El-Hajj II, Harb MI, Sawaya RA.
Am J Clin Oncol. 2006 Feb;29(1):100-1.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16462512&query_hl=1&itool=pubmed_docsum
The authors suggest that patients required to be on thalidomide should be screened for inherited
thrombophilia and should be considered for prophylactic anticoagulation therapy.
NThalidomide in multiple myeloma.
Garcia-Sanz R.
Expert Opin Pharmacother. 2006 Feb;7(2):195-213.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16433584&query_hl=1&itool=pubmed_DocSum
This article reviews the current knowledge of thalidomide in myeloma treatment, focusing
especially on the possible mechanisms of action, clinical results, and adverse events related to this
drug.
NFirst-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone
resorption markers in patients with multiple myeloma.
Tosi P, Zamagni E, Cellini C, Parente R, Cangini D, Tacchetti P, Perrone G, Ceccolini M, Boni P,
Tura S, Baccarani M, Cavo M.
Eur J Haematol. 2006 Feb 15; [Epub ahead of print].
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16480429&query_hl=1&itool=pubmed_docsum
The study found that among all bone resorption markers, urinary N-terminal telopeptide of
collagen I (NTX) and C-terminal telopeptide (serum crosslaps) seem to be strictly related to the
extent of bone involvement in MM. Combined thalidomide + dexamethasone and zoledronic acid
seem to be highly effective in reducing bone resorption in sensitive patients, although the relative
contribution of each drug cannot yet be determined.
NDo new therapeutic approaches (autotransplants, thalidomide, dexamethasone) improve
the survival of patients with multiple myeloma followed in a rheumatology department?
El Mahou S, Attal M, Jamard B, Constantin A, Cantagrel A, Mazieres B, Arnaud C, Laroche M.
Clin Rheumatol. 2006 Mar;25(2):175-82. Epub 2005 Nov 23.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16328086&query_hl=1&itool=pubmed_DocSum
The aim of this study was to determine if survival increased with the usage of new treatments
for MM. Independent analysis showed increased median survival in MM patients treated using
autotransplantation compared with untreated patients. Survival was also longer in MM patients
treated with thalidomide than in untreated patients.
www.myeloma.org
(800) 452 - CURE (2873)
NStimulation of erythropoiesis by thalidomide in multiple myeloma patients: its influence
on FasL, TRAIL and their receptors on erythroblasts.
Grzasko N, Dmoszynska A, Hus M, Soroka-Wojtaszko M.
Haematologica. 2006 Mar;91(3):386-9.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16531263&query_hl=1&itool=pubmed_docsum
The results of this study suggest that thalidomide may stimulate erythropoiesis in MM patients by
decreasing the expression of tumor necrosis factor (TNF) -like ligands/receptors on erythroblasts.
NA systematic review of phase-II trials of thalidomide monotherapy in patients with
relapsed or refractory multiple myeloma.
Glasmacher A, Hahn C, Hoffmann F, Naumann R, Goldschmidt H, von Lilienfeld-Toal M, Orlopp
K, Schmidt-Wolf I, Gorschluter M.
Br J Haematol. 2006 Mar;132(5):584-93.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16445831&query_hl=1&itool=pubmed_docsum
This study found that thalidomide monotherapy achieved complete and partial responses in 29.4%
of patients with relapsed or refractory MM.
NLovastatin and thalidomide have a combined effect on the rate of multiple myeloma cell
apoptosis in short term cell cultures.
Dmoszynska A, Podhorecka M, Klimek P, Grzasko N.
Eur J Clin Pharmacol. 2006 Mar 8; [Epub ahead of print].
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16523333&query_hl=1&itool=pubmed_docsum
The authors conclude that the mixture of lovastatin and thalidomide may increase the rate of MM
cell apoptosis in comparison to the single drug. The precise mechanism of this effect should be
determined by further research.
NThalidomide and hematopoietic-cell transplantation for multiple myeloma.
Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, Fassas A, Zangari M,
Hol mig K, Pineda-Roman M, Lee C, Talamo G, Thertulien R, Kiwan E, Krishna S, Fox M, Crowley J.
N Engl J Med. 2006 Mar 9;354(10):1021-30.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16525139&query_hl=1&itool=pubmed_docsum
The authors concluded that thalidomide, when incorporated into high-dose therapy for myeloma,
increased the frequency of complete responses and extended event-free survival at the expense of
added adverse effects without improving overall survival.
www.myeloma.org
(800) 452 - CURE (2873)
NOral melphalan and prednisone chemotherapy plus thalidomide compared with
melphalan and prednisone alone in elderly patients with multiple myeloma: randomised
controlled trial.
Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M,
Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini
MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M; Italian Multiple Myeloma
Network, GIMEMA.
Lancet. 2006 Mar 11;367(9513):825-31.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list
_uids=16530576&query_hl=1&itool=pubmed_docsum
The authors found that oral melphalan and prednisone plus thalidomide (MPT) is an effective
first-line treatment for elderly patients with MM. Anticoagulant prophylaxis reduces frequency of
thrombosis. Longer follow-up is needed to assess effect on overall survival.
www.myeloma.org
(800) 452 - CURE (2873)
(800)452-CURE(2873)
www.myeloma.org
www.myeloma.org
(800) 452 - CURE (2873)