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Published by the IC
nternational M I
yeloma FT
oundation
INVOLG
UME VII, ISSUE I S
Q1/2010
Novel Therapies Issue
The International Myeloma Foundation (IMF) presents this edition of Citings, our premiere publication featuring the most
up-to-date information on myeloma treatment, focused on the novel therapies currently under study and in use. This edition
corresponds with articles published between December 2009 and March 2010.
It is our hope that CITINGS will be a valuable tool in keeping you informed on the latest developments in myeloma treatment.
Please feel free to contact us at (800) 452-CURE (2873) or visit us on the web at www.myeloma.org.
Susie Novis, President, IMF
Novel Therapies Publications
MARCH 2010
NHigh incidence of arterial thrombosis in young patients treated for multiple myeloma: results of a prospective cohort study.
Libourel EJ, Sonneveld P, van der Holt B, de Maat MP, Leebeek FW.
Blood. 2010 Mar 25. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20339094
This prospective study evaluates the risk of arterial thrombosis in 195 consecutive patients aged 18-65 years with newly diagnosed
myeloma, finding that patients have an increased risk for arterial thrombotic events during and following induction chemotherapy with
either vincristine, doxorubicin and dexamethasone (VAD); thalidomide-AD; or bortezomib-AD . Hypertension, smoking and high
factor VIII levels, possibly reflecting disease activity, contribute to the risk of arterial thrombosis.
NBortezomib and donor lymphocyte infusion in multiple myeloma relapsed after allo-SCT does not result
in durable remissions.
Hoevenaren A, van Vulpen LF, Levenga H, Minnema MC, Raymakers R.
Bone Marrow Transplant. 2010 Mar 22. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20305701
No abstract available.
NMajor Tumor Shrinking and Persistent Molecular Remissions After Consolidation With Bortezomib, Thalidomide,
and Dexamethasone in Patients With Autografted Myeloma.
Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L, Crippa C, De Rosa L, Pregno P, Grasso M, Liberati AM, Caravita T,
Pisani F, Guglielmelli T, Callea V, Musto P, Cangialosi C, Passera R, Boccadoro M, Palumbo A.
J Clin Oncol. 2010 Mar 22. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20308672
The authors investigate the effect on minimal residual disease, by qualitative and real-time quantitative polymerase chain reaction
(RQ-PCR), of a consolidation regimen that includes bortezomib, thalidomide, and dexamethasone (VTD) in patients with myeloma
responding to autologous stem-cell transplantation (auto-SCT), becoming the first study to document the occurrence of persistent
molecular remissions in a proportion of myeloma patients treated without allogeneic transplantation. The authors also find that a major
reduction in tumor load recorded by RQ-PCR after VTD suggests that unprecedented levels of tumor cell reduction can be achieved in
myeloma thanks to new nonchemotherapeutic drugs.
www.myeloma.org
(800) 452 - CURE (2873)
Funded by unrestricted educational grants from Celgene Corporation and Millennium: The Takeda Oncology Company.

NPharmacological Properties of Thalidomide and Its Analogues.
De Sanctis JB, Mijares M, Suárez A, Compagnone R, Garmendia J, Moreno D, Salazar-Bookaman M.
Recent Pat Inflamm Allergy Drug Discov. 2010 Mar 22. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20307255
In this review, the authors explore the current trend of the different structures, the new patents, and the possible new applications in
different pathologies of novel agents including thalidomide and lenalidomide.
NPharmacokinetic and pharmacodynamic study of two doses of bortezomib in patients with relapsed multiple myeloma.
Reece DE, Sullivan D, Lonial S, Mohrbacher AF, Chatta G, Shustik C, Burris H 3rd, Venkatakrishnan K, Neuwirth R, Riordan WJ,
Karol M, von Moltke LL, Acharya M, Zannikos P, Keith Stewart A.
Cancer Chemother Pharmacol. 2010 Mar 20. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20306195
The authors find that bortezomib pharmacokinetics change with repeat dose administration, characterized by a reduction in plasma
clearance and associated increase in systemic exposure. Their findings support the current clinical dosing regimen.
NConsensus guidelines for the optimal management of adverse events in newly diagnosed, transplant-ineligible patients
receiving melphalan and prednisone in combination with thalidomide (MPT) for the treatment of multiple myeloma.
Palumbo A, Davies F, Kropff M, Bladé J, Delforge M, Leal da Costa F, Garcia Sanz R, Schey S, Facon T, Morgan G, Moreau P.
Ann Hematol. 2010 Mar 16. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20232066
This article outlines both evidence- and consensus-based recommendations discussed by a panel of experts in order to provide a
practical guide for physicians addressing the effective management of newly diagnosed, transplant-ineligible myeloma patients receiving
thalidomide therapy.
NTHADD Plus High Dose Therapy And Autologous Stem Cell Transplantation Does Not Appear Superior To THADD Plus
Maintenance In Elderly Patietns With De Novo Multiple Myeloma.
Offidani M, Leoni P, Corvatta L, Polloni C, Gentili S, Savini A, Alesiani F, Brunori M, Catarini M, Visani G, Samori A, Burattini M,
Centurioni R, Montanari M, Fraticelli P, Ruggieri M, Falcioni S, Galieni P.
Eur J Haematol. 2010 Mar 11. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20331733
With the aim to address the issue whether high dose therapy (HDT) is required after new drug combinations to improve outcome of
elderly newly diagnosed myeloma patients, the authors compare the toxicity and the outcome of ThaDD plus maintenance to those of
ThaDD plus HDT-ASCT. Their results suggest that in elderly myeloma patients ThaDD plus HDT, though it significantly increases
complete response rate, seems to be equivalent to ThaDD plus maintenance in terms of time to progression, progression free survival,
and overall survival.
NPhase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenström
macroglobulinemia.
Ghobrial IM, Hong F, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Harris B, Sam A,
Anderson KC, Richardson PG, Treon SP, Weller E, Matous J.
J Clin Oncol. 2010 Mar 10;28(8):1422-8. [Epub 2010 Feb 8.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20142586
This study aims to determine activity and safety of weekly bortezomib and rituximab in patients with relapsed/refractory Waldenström
macroglobulinemia (WM). The authors conclude that the combination shows significant activity and minimal neurologic toxicity
in this patient group.
NAdvances in treatment for relapses and refractory multiple myeloma.
Richards T, Weber D.
Med Oncol. 2010 Mar 6. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20213220
This article reviews the current role for thalidomide, lenalidomide, and bortezomib-based combinations for patients with relapsed
and/or refractory myeloma.
www.myeloma.org
(800) 452 - CURE (2873)

NHematopoietic stem cell transplantation for multiple myeloma beyond 2010.
Bladé J, Rosiñol L, Cibeira MT, Rovira M, Carreras E.
Blood. 2010 Mar 4. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20203260
The authors discuss the development of novel reduced-intensity preparative regimens (including use of bortezomib) and peri- and
-post-transplant strategies aimed at minimizing graft-versus-host disease and enhancing the graft-versus-myeloma effect as key issues in
the future treatment of myeloma.
NLong-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the intergroupe
francophone du myelome, southwest oncology group, and university of arkansas for medical sciences.
Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, Durie BG, Harousseau JL.
J Clin Oncol. 2010 Mar 1;28(7):1209-14. [Epub 2010 Jan 19.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20085933
These long-term follow-up data of transplantation trials provide a crucial framework of reference for outcome reporting of novel
agent-based trials (including thalidomide and bortezomib) reportedly exhibiting remarkable short-term efficacy approaching high-dose
therapy results.
NThe novel inhibitor of histone deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple
myeloma (MM) cells.
Mandl-Weber S, Meinel F, Jankowsky R, Oduncu F, Schmidmaier R, Baumann P.
Br J Haematol. 2010 Mar 1. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20201941
The authors observe synergistic effects for combinations of resminostat with melphalan and the proteasome inhibitors bortezomib and
S-2209.
NBortezomib restores stroma-mediated APO2L/TRAIL apoptosis resistance in multiple myeloma.
Perez LE, Parquet N, Meads M, Anasetti C, Dalton W.
Eur J Haematol. 2010 Mar;84(3):212-22. [Epub 2009 Nov 17.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19922463
The authors test whether bortezomib can reverse the APO2L/TRAIL environmental mediated-immune resistance. Their findings
provide the rationale to combine bortezomib and APO2L/TRAIL to disrupt the influence of the stroma microenvironment on
myeloma cells.
NDifferential activities of thalidomide and isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells.
Holstein SA, Tong H, Hohl RJ.
Leuk Res. 2010 Mar;34(3):344-51. [Epub 2009 Jul 30.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19646757
The authors evaluate the interactions between thalidomide and the isoprenoid biosynthetic pathway (IBP) inhibitors in myeloma cells,
with findings that provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP.
NDKK1 correlates with response and predicts rapid relapse after autologous stem cell transplantation in multiple myeloma.
Lemaire O, Attal M, Bourin P, Laroche M.
Eur J Haematol. 2010 Mar;84(3):276-7. [Epub 2009 Nov 5.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19891699
No abstract available.
www.myeloma.org
(800) 452 - CURE (2873)

NImpact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple
myeloma treated with lenalidomide plus dexaméthasone.
Avet-Loiseau H, Soulier J, Fermand JP, Yakoub-Agha I, Attal M, Hulin C, Garderet L, Belhadj K, Dorvaux V, Minvielle S, Moreau P;
IFM and MAG groups.
Leukemia. 2010 Mar;24(3):623-8. [Epub 2010 Jan 14.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20072152
This retrospective analysis investigates the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment
on outcomes in heavily pretreated patients with relapsed or refractory myeloma treated with lenalidomide plus dexamethasone.
NLenalidomide for the treatment of cryoglobulinemia and undifferentiated spondyloarthropathy in a patient
with multiple myeloma.
Lin RJ, Curran JJ, Zimmerman TM, Song J, Niewold TB, Sweiss NJ.
J Clin Rheumatol. 2010 Mar;16(2):90-1.
:
http://www.ncbi.nlm.nih.gov/pubmed/20130475
No abstract available.
NReversal of dialysis-dependent renal failure in patients with advanced multiple myeloma:
single institutional experiences over 8 years.
Matsue K, Fujiwara H, Iwama K, Kimura S, Yamakura M, Takeuchi M.
Ann Hematol. 2010 Mar;89(3):291-7. [Epub 2009 Aug 20.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19693498
The authors study the impact on the reversibility of high-dose dexamethasone and/or thalidomide-containing regimen in 12 newly
diagnosed myeloma patients and find that dialysis-dependent renal failure is reversible in most myeloma patients, even if the patient
is in advanced age.
NSafety and efficacy of bortezomib-based regimens for multiple myeloma patients with renal impairment:
a retrospective study of Italian Myeloma Network GIMEMA.
Morabito F, Gentile M, Ciolli S, Petrucci MT, Galimberti S, Mele G, Casulli AF, Mannina D, Piro E, Pinotti G, Palmieri S, Catalano L,
Callea V, Offidani M, Musto P, Bringhen S, Baldini L, Tosi P, Di Raimondo F, Boccadoro M, Palumbo A, Cavo M.
Eur J Haematol. 2010 Mar;84(3):223-8. [Epub 2009 Nov 23.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19930441
This retrospective analysis investigates the safety and efficacy of bortezomib-based therapy in myeloma patients with renal impairment
(RI). The authors conclude that bortezomib-based regimens are safe and effective and should be considered as appropriate treatment
options for myeloma patients with any degree of RI.
NSevere pulmonary complications after bortezomib treatment in multiple myeloma.
Dun X, Yuan Z, Fu W, Zhang C, Hou J.
Hematol Oncol. 2010 Mar;28(1):49-52.
:
http://www.ncbi.nlm.nih.gov/pubmed/19728395
No abstract available.
NVorinostat enhances the antimyeloma effects of melphalan and bortezomib.
Campbell RA, Sanchez E, Steinberg J, Shalitin D, Li ZW, Chen H, Berenson JR.
Eur J Haematol. 2010 Mar;84(3):201-11. [Epub 2009 Nov 18.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19929977
The authors find that vorinostat enhances the anti-myeloma activity of melphalan and bortezomib in vitro and in vivo, providing
rationale for further evaluation of vorinostat in combination with chemotherapeutic agents and bortezomib for the treatment
of myeloma.
www.myeloma.org
(800) 452 - CURE (2873)

FEBRUARY 2010
NThalidomide-Dexamethasone As Induction Therapy Prior To Autologous Stem-Cell Transplantation In Patients With Newly
Diagnosed Multiple Myeloma And Renal Insufficiency.
Tosi P, Zamagni E, Tacchetti P, Ceccolini M, Perrone G, Brioli A, Pallotti MC, Pantani L, Petrucci A, Baccarani M, Cavo M.
Biol Blood Marrow Transplant. 2010 Feb 27. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20197100
The authors evaluate the efficacy and the toxicity of thalidomide-dexamethasone (thal-dex) as induction therapy prior to autologous
peripheral blood stem-cell (PBSC) transplantation in newly diagnosed myeloma patients with renal insufficiency. They find that thal-
dex is effective and safe in patients with newly diagnosed myeloma and renal insufficiency; given the relationship between recovery of
renal function and response to induction treatment, more intensive thal+bortezomib regimens could be explored in order to rescue a
higher number of patients.
NThalidomide-Dexamethasone As Up-Front Therapy For Newly Diagnosed Multiple Myeloma Patients: Thrombophilic
Alterations, Thrombotic Complications And Thromboprophylaxis With Low-Dose Warafin.
Cini M, Zamagni E, Valdré L, Palareti G, Patriarca F, Tacchetti P, Legnani C, Catalano L, Masini L, Tosi P, Gozzetti A, Cavo M.
Eur J Haematol. 2010 Feb 23. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20192986
The authors address the issue of pathogenesis of thalidomide-induced VTE as not well recognized and the role of prothrombotic
factors, especially of thrombophilic abnormalities, as not yet determined. On the basis of their data, they do not recommend a baseline
thrombophilic work up in myeloma patients receiving up-front thalidomide-dexamethasone. For these patients, fixed low-dose warfarin
may be a valuable prophylaxis against VTE.
NLenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide
according to renal function and effect on renal impairment.
Dimopoulos MA, Christoulas D, Roussou M, Kastritis E, Migkou M, Gavriatopoulou M, Matsouka C, Mparmparoussi D, Psimenou E,
Grapsa I, Efstathiou E, Terpos E.
Eur J Haematol. 2010 Feb 20. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20192988
The authors study the effect of the lenalidomide and dexamethasone regimen (LenDex) on renal impairment (RI) and renal
reversibility. They find that with dosing of lenalidomide according to renal function, LenDex can be administered to patients with
RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in
approximately 40% of patients with RI.
NThe evolution and impact of therapy in multiple myeloma.
Laubach JP, Richardson PG, Anderson KC.
Med Oncol. 2010 Feb 19. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20169425
This review highlights important historic landmarks as well as more recent events that have played an important role in the evolution
of myeloma therapy, including the use of thalidomide, lenalidomide, and bortezomib.
NLenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a
comparative analysis of 411 patients.
Gay F, Hayman SR, Lacy MQ, Buadi F, Gertz MA, Kumar S, Dispenzieri A, Mikhael JR, Bergsagel PL, Dingli D, Reeder CB, Lust JA,
Russell SJ, Roy V, Zeldenrust SR, Witzig TE, Fonseca R, Kyle RA, Greipp PR, Stewart AK, Rajkumar SV.
Blood. 2010 Feb 18;115(7):1343-50. [Epub 2009 Dec 11.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20008302
This retrospective study compares the efficacy and toxicity of lenalidomide plus dexamethasone (len/dex) versus thalidomide plus
dexamethasone (thal/dex) as initial therapy for newly diagnosed myeloma. The authors conclude that len/dex appears well-tolerated and
more effective than thal/dex.
www.myeloma.org
(800) 452 - CURE (2873)

NA randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose
melphalan, followed by thalidomide maintenance in patients with multiple myeloma.
Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de
Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van
Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON).
Blood. 2010 Feb 11;115(6):1113-20. [Epub 2009 Oct 30.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19880501
The phase III trial evaluates the effect of thalidomide during induction treatment and as maintenance in myeloma patients who are
transplant candidates and finds that patients randomized to thalidomide had strongly reduced survival after relapse.
NA TAD better for myeloma therapy?
Giralt S.
Blood. 2010 Feb 11;115(6):1109-10.
:
http://www.ncbi.nlm.nih.gov/pubmed/20150417
The author reports on the results of HOVON-50, a phase 3 randomized trial, that together with other randomized and
nonrandomized trials establishes a definitive role for thalidomide as induction therapy in conjunction with dexamethasone,
anthracyclines, and alkylating agents.
NBortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in
untreated multiple myeloma patients.
Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T,
Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M.
J Clin Oncol. 2010 Feb 10;28(5):800-7. [Epub 2010 Jan 4.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20048187
The authors evaluate the effect of bortezomib as induction therapy before autologous transplantation, followed by lenalidomide as
consolidation-maintenance in myeloma patients. They find it to be an effective regimen.
NEnhancing activity and overcoming chemoresistance in hematologic malignancies with bortezomib: preclinical mechanistic
studies.
Reddy N, Czuczman MS.
Ann Oncol. 2010 Feb 4. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20133382
This review indicates the potential utility of proteasome inhibition, explains the mechanisms responsible for the observed clinical
activity of bortezomib-based regimens, and elucidates novel therapeutic approaches through identification of combinations of agents
with complimentary mechanisms of action.
NSuperior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in
subsequent trial 2006-66 with bortezomib, lenalidomide and dexamethasone (VRD) maintenance.
Nair B, van Rhee F, Shaughnessy JD Jr, Anaissie E, Szymonifka J, Hoering A, Alsayed Y, Waheed S, Crowley J, Barlogie B.
Blood. 2010 Feb 2. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20124509
The authors report here on the results of successor trial 2006-66, employing bortezomib-lenalidomide-dexamethasone maintenance for
3 years, versus bortezomib-thalidomide-dexamethasone in year 1 and thalidomide-dexamethasone in years 2 and 3. They conclude that
robustness of the gene expression profiling risk model should be exploited in clinical trials aimed at improving the notoriously poor
outcome in high-risk myeloma.
www.myeloma.org
(800) 452 - CURE (2873)

NBortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy
before autologous transplant in patients with myeloma.
Corso A, Barbarano L, Mangiacavalli S, Spriano M, Alessandrino EP, Cafro AM, Pascutto C, Varettoni M, Bernasconi P, Grillo G, Carella
AM, Montalbetti L, Lazzarino M, Morra E.
Leuk Lymphoma. 2010 Feb;51(2):236-42.
:
http://www.ncbi.nlm.nih.gov/pubmed/20001242
This phase II trial investigates the efficacy of bortezomib plus dexamethasone (Vel-Dex) as induction therapy in patients with myeloma
and seeks to define the role of intensification before transplantation. The authors conclude that Vel-Dex produces high response rates,
improves stem cell collection, and overcomes the need for intensification before autologous transplantation.
NComplications of multiple myeloma therapy, part 2: risk reduction and management of venous thromboembolism,
osteonecrosis of the jaw, renal complications, and anemia.
Niesvizky R, Badros AZ.
J Natl Compr Canc Netw. 2010 Feb;8 Suppl 1:S13-20.
:
http://www.ncbi.nlm.nih.gov/pubmed/20141670
This article discusses the common myeloma treatment complications-- venous thromboembolism, osteonecrosis of the jaw, renal
failure, and anemia-- in detail, and provides strategies for health care providers to best prevent, identify, and manage them.
NConstitutive down-regulation of Osterix in osteoblasts from myeloma patients: in vitro effect of Bortezomib and
Lenalidomide.
De Matteo M, Brunetti AE, Maiorano E, Cafforio P, Dammacco F, Silvestris F.
Leuk Res. 2010 Feb;34(2):243-9. [Epub 2009 Aug 4.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19656567
The authors' findings provide additional evidence suggesting that, at least in vitro, bortezomib promotes osteoblast maturation.
NThe current status and future of multiple myeloma in the clinic.
Jagannath S, Kyle RA, Palumbo A, Siegel DS, Cunningham S, Berenson J.
Clin Lymphoma Myeloma Leuk. 2010 Feb;10(1):28-43.
:
http://www.ncbi.nlm.nih.gov/pubmed/20223727
This review highlights challenges in the clinic and newer approaches under evaluation for the treatment and/or management of patients
with MGUS, smoldering myeloma, and myeloma, including the use of thalidomide, lenalidomide, and bortezomib.
NEffects of induction with novel agents versus conventional chemotherapy on mobilization and autologous stem cell
transplant outcomes in multiple myeloma.
Benson DM Jr, Panzner K, Hamadani M, Hofmeister CC, Bakan CE, Smith MK, Elder P, Krugh D, O'Donnell L, Devine SM.
Leuk Lymphoma. 2010 Feb;51(2):243-51.
:
http://www.ncbi.nlm.nih.gov/pubmed/20038230
The authors compare conventional induction regimens with novel agent-based induction strategies (including use of thalidomide,
lenalidomide, and bortezomib) and the associated effects on stem cell mobilization and HDC/SCT outcome in 224 patients. They
find that an improvement in overall survival after HDC/SCT may be related to induction therapy with novel agents as opposed to
chemotherapy.
NIn the age of novel therapies, what defines high-risk multiple myeloma?
Badros AZ.
J Natl Compr Canc Netw. 2010 Feb;8 Suppl 1:S28-34.
:
http://www.ncbi.nlm.nih.gov/pubmed/20141672
The author discusses the advent of risk-based therapy in the treatment of myeloma, and the role of novel agents, such as bortezomib,
thalidomide, and lenalidomide, within this new treatment model.
www.myeloma.org
(800) 452 - CURE (2873)

NInduction Treatment With Cyclophosphamide, Thalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: A
Phase II Study.
Yang DH, Kim YK, Sohn SK, Chung JS, Joo YD, Lee JH, Lee JL, Ahn JS, Moon JH, Shin HJ, Choi YJ, Lee WS, Kim HJ, Lee JJ.
Clin Lymphoma Myeloma Leuk. 2010 Feb;10(1):62-7.
:
http://www.ncbi.nlm.nih.gov/pubmed/20223731
This study finds that an induction therapy of cyclophosphamide, thalidomide, and dexamethasone results in favorable response with
tolerable toxicity in patients with newly diagnosed myeloma, and does not affect the yield of stem cell collection.
NLenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK
(NKp44(+)) and T (HLA-DR(+)) cells.
Lioznov M, El-Cheikh J Jr, Hoffmann F, Hildebrandt Y, Ayuk F, Wolschke C, Atanackovic D, Schilling G, Badbaran A, Bacher U, Fehse
B, Zander AR, Blaise D, Mohty M, Kröger N.
Bone Marrow Transplant. 2010 Feb;45(2):349-53. [Epub 2009 Jul 6.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19584825
The authors investigate efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59
years and relapse after allo-SCT. In their study, response is achieved in 66% of patients, and they find that immunomonitoring after
lenalidomide shows significant increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells, as well as regulatory T cells (CD4(+),
CD25(+), CD127(lo)), supporting an immunomodulating anti-myeloma effect of lenalidomide.
NOsteoblastogenesis and tumor growth in myeloma.
Yaccoby S.
Leuk Lymphoma. 2010 Feb;51(2):213-20.
:
http://www.ncbi.nlm.nih.gov/pubmed/20038269
The author reviews the role of osteoblastogenesis suppression in the treatment of myeloma and concludes that increased osteoblast
activity (including the use of bortezomib) is a promising approach to treat myeloma bone disease and simultaneously control myeloma
development and progression.
NPeripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations.
Mohty B, El-Cheikh J, Yakoub-Agha I, Moreau P, Harousseau JL, Mohty M.
Haematologica. 2010 Feb;95(2):311-9.
:
http://www.ncbi.nlm.nih.gov/pubmed/20139393
This review discusses the pathogenesis, incidence, risk factors, diagnosis, characteristics, and management of peripheral neuropathy
related to new myeloma drugs, primarily bortezomib and thalidomide.
NPresentation and survival of patients with severe acute kidney injury and multiple myeloma: a 20-year experience from a
single centre.
Haynes RJ, Read S, Collins GP, Darby SC, Winearls CG.
Nephrol Dial Transplant. 2010 Feb;25(2):419-26. [Epub 2009 Sep 19.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19767634
The authors document the natural history of 107 myeloma patients referred to a large regional renal unit over a 20-year period
and investigate factors associated with survival over a long period of time. Their analysis highlights the need for clinical trials of
novel chemotherapy regimens in this complicated group of patients; the advent of efficacious low toxicity chemotherapy (such as
thalidomide) and new dialysis techniques may radically alter the outcome of this group of patients.
NThe role of maintenance therapy in the treatment of multiple myeloma.
Badros AZ.
J Natl Compr Canc Netw. 2010 Feb;8 Suppl 1:S21-7.
:
http://www.ncbi.nlm.nih.gov/pubmed/20141671
The author discusses the emerging role of the novel agents thalidomide, lenalidomide, and bortezomib as maintenance therapy in the
treatment of myeloma.
www.myeloma.org
(800) 452 - CURE (2873)

NWeekly bortezomib, pegylated liposomal doxorubicin, and dexamethasone is a safe and effective therapy for elderly patients
with relapsed/refractory multiple myeloma.
Gozzetti A, Fabbri A, Oliva S, Marchini E, Bocchia M, Defina M, Lauria F.
Clin Lymphoma Myeloma Leuk. 2010 Feb;10(1):68-72.
:
http://www.ncbi.nlm.nih.gov/pubmed/20223732
The authors pursue the first-ever evaluation of the synergic, additive effect of bortezomib and pegylated liposomal doxorubicin (PLD)
in an elderly group of patients with relapsed/refractory myeloma. They conclude that PLD is safe and effective in elderly patients with
resistant-relapsing myeloma.
JANUARY 2010
NRole of the TNF-alpha promoter polymorphisms for development of multiple myeloma and clinical outcome in thalidomide
plus dexamethasone.
Du J, Yuan Z, Zhang C, Fu W, Jiang H, Chen B, Hou J.
Leuk Res. 2010 Jan 30. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20122728
The authors study the role of TNF-alpha promoter polymorphisms in the development of myeloma, evaluating patients treated with a
thalidomide-dexamethasone regimen.
NCombination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity
in multiple myeloma.
Chauhan D, Singh AV, Ciccarelli B, Richardson PG, Palladino MA, Anderson KC.
Blood. 2010 Jan 28;115(4):834-45. [Epub 2009 Nov 13.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19965674
The authors demonstrate that combining NPI-0052 and lenalidomide induces synergistic anti-myeloma activity in vitro using
myeloma-cell lines or patient myeloma cells.
NStem cell transplant in multiple myeloma: impact of response failure with thalidomide or lenalidomide induction.
Gertz MA, Kumar S, Lacy MQ, Dispenzieri A, Dingli D, Hayman SR, Buadi FK, Hogan WJ.
Blood. 2010 Jan 20. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20089967
This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response after
induction therapy with a regimen that contains thalidomide or lenalidomide.
NBortezomib down-regulates the osterix expression by osteoblasts in the myeloma microenvironment: Implications into
osteoblast function in myeloma bone disease.
Terpos E.
Leuk Res. 2010 Jan 12. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20074800
No abstract available.
NBortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients
with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM).
Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb
B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M;
Intergroupe Francophone du Myélome (IFM).
Blood. 2010 Jan 7;115(1):32-7. [Epub 2009 Nov 2.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19884643
This phase II study finds that bortezomib-HDM is a safe and promising conditioning regimen. Randomized studies are needed
to assess whether this conditioning regimen is superior to HDM alone.
www.myeloma.org
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NMelphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of multicenter phase I/
II trial.
Palumbo A, Larocca A, Genuardi M, Kotwica K, Gay F, Rossi D, Benevolo G, Magarotto V, Cavallo F, Bringhen S, Rus C, Masini L,
Iacobelli M, Gaidano G, Mitsiades C, Anderson K, Boccadoro M, Richardson P; for the Italian Multiple Myeloma Network, GIMEMA.
Haematologica. 2010 Jan 6. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20053869
This phase I/II trial concludes that the combination of oral melphalan, thalidomide, and defibrotide shows anti-tumor activity with
favorable tolerability.
NDexamethasone Synergizes with Lenalidomide to Inhibit Multiple Myeloma Tumor Growth, But Reduces Lenalidomide-
Induced Immunomodulation of T and NK Cell Function.
Gandhi AK, Kang J, Capone L, Parton A, Wu L, Zhang LH, Mendy D, Lopez-Girona A, Tran T, Sapinoso L, Fang W, Xu S, Hampton G,
Bartlett JB, Schafer P.
Curr Cancer Drug Targets. 2010 Jan 1. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20088798
To determine the effect of dexamethasone on the antimyeloma effects of lenalidomide, the authors test in vitro proliferation, tumor
suppressor gene expression, caspase activity, cell cycling, and apoptosis levels in a series of myeloma and plasma cell leukemia cell lines
treated with lenalidomide and dexamethasone, alone or in combination. Their findings further elucidate the mechanism of action
of lenalidomide and dexamethasone in myeloma, and suggest that use of low-dose dexamethasone with lenalidomide may retain the
antiproliferative effect of lenalidomide while permitting greater immunomodulatory effects of this combination regimen.
NSurvival effect of venous thromboembolism in patients with multiple myeloma treated with lenalidomide and high-dose
dexamethasone.
Zangari M, Tricot G, Polavaram L, Zhan F, Finlayson A, Knight R, Fu T, Weber D, Dimopoulos MA, Niesvizky R, Fink L.
J Clin Oncol. 2010 Jan 1;28(1):132-5. [Epub 2009 Nov 9.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19901114
The authors conduct a retrospective analysis of the survival effect of venous thromboembolism (VTE) development in patients with
multiple myeloma and find that myeloma patients treated with lenalidomide and high-dose dexamethasone who developed a VTE do
not experience shorter overall survival or time to progression.
NBortezomib and zoledronic acid on angiogenic and vasculogenic activities of bone marrow macrophages in patients with
multiple myeloma.
Moschetta M, Di Pietro G, Ria R, Gnoni A, Mangialardi G, Guarini A, Ditonno P, Musto P, D'Auria F, Ricciardi MR, Dammacco F,
Ribatti D, Vacca A.
Eur J Cancer. 2010 Jan;46(2):420-9. [Epub 2009 Nov 13.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19914061
This study provides evidence that the exposure of bone marrow macrophages in myelomaduring the treatment with zoledronic acid
and bortezomib, alone and or in combination, impacts their angiogenic and vasculogenic properties, suggesting that these cells may be
considered as a target of both drugs in myeloma patients.
NEnhanced antimyeloma cytotoxicity by the combination of arsenic trioxide and bortezomib is further potentiated by p38
MAPK inhibition.
Wen J, Feng Y, Huang W, Chen H, Liao B, Rice L, Preti HA, Kamble RT, Zu Y, Ballon DJ, Chang CC.
Leuk Res. 2010 Jan;34(1):85-92. [Epub 2009 Jul 15.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19608275
The authors study the cytotoxicity of bortezomib, ATO, and ATO+bortezomib with or without inhibiting p38 MAPK, along with
associated molecular changes in myeloma cells. Their results suggest the opportunity for using p38 MAPK inhibition to enhance the
efficacy of ATO+bortezomib in myeloma.
www.myeloma.org
(800) 452 - CURE (2873)

NLenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy
for newly diagnosed multiple myeloma: an open-label randomised controlled trial.
Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; Eastern
Cooperative Oncology Group.
Lancet Oncol. 2010 Jan;11(1):29-37. [Epub 2009 Oct 21.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19853510
The authors study whether low-dose dexamethasone in combination with lenalidomide is non-inferior to and has lower toxicity
than high-dose dexamethasone plus lenalidomide. They find that in newly diagnosed myeloma patients, lenalidomide plus low-
dose dexamethasone is associated with better short-term overall survival and with lower toxicity than lenalidomide plus high-dose
dexamethasone.
NLenalidomide (Revlimid) combined with continuous oral cyclophosphamide (endoxan) and prednisone (REP) is effective
in lenalidomide/dexamethasone-refractory myeloma.
van de Donk NW, Wittebol S, Minnema MC, Lokhorst HM.
Br J Haematol. 2010 Jan;148(2):335-7.
:
http://www.ncbi.nlm.nih.gov/pubmed/20085583
No abstract available.
NMechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma.
Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, Prince HM.
Leukemia. 2010 Jan;24(1):22-32. [Epub 2009 Nov 12.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19907437
The authors discuss the nature of immunomodulatory drugs (IMiDs) and conclude that much is yet to be elucidated regarding the
complex interplay of immunomodulatory cytokines that occurs in vivo, which ultimately dictates the net effects of IMiDs in myeloma
the understanding of which is necessary to facilitate optimal manipulation of these drugs in future myeloma management.
NNew developments in the treatment of patients with multiple myeloma.
Minnema MC, van der Spek E, van de Donk NW, Lokhorst HM.
Neth J Med. 2010 Jan;68(1):24-32.
:
http://www.ncbi.nlm.nih.gov/pubmed/20103818
This review focuses on the studies of thalidomide, bortezomib, and lenalidomide that have changed the treatment guidelines for
patients with myeloma.
NNew treatments for myeloma.
Azaïs I, Brault R, Debiais F.
Joint Bone Spine. 2010 Jan;77(1):20-6. [Epub 2009 Dec 23.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20031467
The authors discuss how the management of myeloma has benefited substantially from the introduction of bortezomib, thalidomide,
and lenalidomide.
NRapid improvement in renal function in patients with multiple myeloma and renal failure treated with bortezomib.
Qayum A, Aleem A, Al Diab AR, Niaz F, Al Momen AK.
Saudi J Kidney Dis Transpl. 2010 Jan;21(1):63-8.
:
http://www.ncbi.nlm.nih.gov/pubmed/20061695
The authors report six cases of renal failure secondary to myeloma treated with bortezomib. They find that bortezomib may have an
effect on the kidneys in reversal of renal failure, other than its anti-myeloma effect, and conclude that bortezomib appears to be an
effective treatment for patients with advanced myeloma and renal failure irrespective of performance status and age.
www.myeloma.org
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N"Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for
nontransplant candidates in patients with previously untreated multiple myeloma.
Gasparetto C, Gockerman JP, Diehl LF, de Castro CM, Moore JO, Long GD, Horwitz ME, Keogh G, Chute JP, Sullivan KM, Neuwirth
R, Davis PH, Sutton LM, Anderson RD, Chao NJ, Rizzieri D.
Biol Blood Marrow Transplant. 2010 Jan;16(1):70-7. [Epub 2009 Sep 3.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19733251
The authors find that short-course course bortezomib, melphalan, prednisone (VMP) is highly effective and generally well tolerated,
both as initial treatment in non-ASCT patients and induction prior to ASCT, and that VMP does not negatively affect stem cell
collection.
NTowards a new standard of care for patients with myeloma?
Palumbo A, Gay F.
Lancet Oncol. 2010 Jan;11(1):3-4. [Epub 2009 Oct 21.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19853511
Comment on: Lancet Oncol. 2010 Jan;11(1):29-37.
NTreatment outcome of thalidomide based regimens in newly diagnosed and relapsed/refractory non-transplant multiple
myeloma patients: a single center experience from Thailand.
Niparuck P, Sorakhunpipitkul L, Atichartakarn V, Chuncharunee S, Ungkanont A, Aungchaisuksiri P, Puavilai T, Jootar S.
J Hematol Oncol. 2010 Jan 5;3:1.
:
http://www.ncbi.nlm.nih.gov/pubmed/20051128
The authors conduct a retrospective study of 42 consecutive patients with newly diagnosed and relapsed/refractory myeloma treated
with thalidomide-based induction regimens followed by thalidomide maintenance therapy. They find that prolonged thalidomide
therapy enhances survival rate and less frequently leads to serious toxicity in non-transplant myeloma patients.
NBortezomib.
Einsele H.
Recent Results Cancer Res. 2010;184:173-87.
:
http://www.ncbi.nlm.nih.gov/pubmed/20072838
The author discusses bortezomib's role in the treatment of newly diagnosed as well as relapsed/progressive myeloma, and the major
impact it has had on improvement in the treatment of myeloma in the last few years.
NCurrent multiple myeloma treatment strategies with novel agents: a European perspective.
Ludwig H, Beksac M, Bladé J, Boccadoro M, Cavenagh J, Cavo M, Dimopoulos M, Drach J, Einsele H, Facon T, Goldschmidt H,
Harousseau JL, Hess U, Ketterer N, Kropff M, Mendeleeva L, Morgan G, Palumbo A, Plesner T, San Miguel J, Shpilberg O, Sondergeld
P, Sonneveld P, Zweegman S.
Oncologist. 2010;15(1):6-25. [Epub 2010 Jan 19.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20086168
This review presents an overview of the most recent data with thalidomide, lenalidomide, and bortezomib, and summarizes European
treatment practices incorporating these novel agents.
NResolving a double standard for risk management of thalidomide: an evaluation of two different risk management
programmes in Japan.
Ooba N, Sato T, Watanabe H, Kubota K.
Drug Saf. 2010;33(1):35-45.
http://www.ncbi.nlm.nih.gov/pubmed/20000865
The authors evaluate the difference between the Thalidomide Education and Risk Management System and the Safety Management
System for Unapproved Drugs (SMUD) in order to establish a way to resolve the "double standard" for risk management of
thalidomide treatment in Japan. They conclude that SMUD should be improved so that all patients are monitored in a way that results
in a similar level of risk management.
www.myeloma.org
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NThalidomide and bortezomib overcome the prognostic significance of proliferative index in multiple myeloma.
Minarik J, Scudla V, Bacovsky J, Zemanova M, Pika T, Ordeltova M, Langova K.
Neoplasma. 2010;57(1):8-14.
:
http://www.ncbi.nlm.nih.gov/pubmed/19895166
The authors analyze proliferative index of myeloma plasmocytes (PC-PI) in a cohort of 217 patients with myeloma treated with
conventional chemotherapy and novel agents thalidomide and bortezomib. Their results suggest that the treatment of myeloma with
novel agents overcomes the prognostic significance of PC-PI and should be used in all myeloma patients.
DECEMBER 2009
NHow I treat multiple myeloma in younger patients.
Stewart AK, Richardson PG, San-Miguel JF.
Blood. 2009 Dec 24;114(27):5436-43. [Epub 2009 Oct 27.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19861683
The authors discuss induction therapy, including the use of bortezomib, lenalidomide, and thalidomide, as part of their treatment goal
with younger myeloma patients to target a durable complete remission.
NVMP (Bortezomib, Melphalan, and Prednisone) is active and well tolerated in newly diagnosed patients with multiple
myeloma with moderately impaired renal function, and results in reversal of renal impairment: cohort analysis of the phase
III VISTA study.
Dimopoulos MA, Richardson PG, Schlag R, Khuageva NK, Shpilberg O, Kastritis E, Kropff M, Petrucci MT, Delforge M, Alexeeva J,
Schots R, Masszi T, Mateos MV, Deraedt W, Liu K, Cakana A, van de Velde H, San Miguel JF.
J Clin Oncol. 2009 Dec 20;27(36):6086-93. [Epub 2009 Oct 26.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19858394
This study finds that bortezomib plus melphalan and prednisone is a feasible, active, and well-tolerated treatment option for previously
untreated myeloma patients with moderate renal impairment, resulting in 44% renal impairment reversal.
NInhibition of mTORC1 activity by REDD1 induction in myeloma cells resistant to bortezomib cytotoxicity.
Decaux O, Clément M, Magrangeas F, Gouraud W, Charbonnel C, Campion L, Loiseau HA, Minvielle S.
Cancer Sci. 2009 Dec 11. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20100206
The authors use gene expression profiling to identify early responsive genes induced by bortezomib in resistant myeloma cells. Their
results identify a possible novel mechanism of bortezomib resistance in myeloma patients mediated by REDD1 overexpression
involving inhibition of mTORC1 activity, and suggest that the use of mammalian target of rapamycin inhibitors in myeloma patients
could be deleterious.
NFuture directions in immunomodulatory therapy.
Lonial S.
Med Oncol. 2009 Dec 11. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20012563
The author discusses the roles of thalidomide, lenalidomide, and bortezomib in the management of patients with myeloma in all phases
of their disease.
NBortezomib, thalidomide, dexamethasone induction therapy followed by melphalan, prednisolone, thalidomide
consolidation therapy as a first line of treatment for patients with multiple myeloma who are non-transplant candidates:
results of the Korean Multiple Myeloma Working Party (KMMWP).
Eom HS, Kim YK, Chung JS, Kim K, Kim HJ, Kim HY, Jin JY, Do YR, Oh SJ, Suh C, Seong CM, Kim CS, Lee DS, Lee JH.
Ann Hematol. 2009 Dec 10. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20012045
The authors find that as first-line therapy, bortezomib-thalidomide-dexamethasone followed by melphalan-prednisolone-thalidomide
has the potential to provide high-quality responses with durable remission among elderly and high-risk myeloma patients.
www.myeloma.org
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NTreatment response to bortezomib in multiple myeloma correlates with plasma hepatocyte growth factor concentration and
bone marrow thrombospondin concentration.
Ludek P, Hana S, Zdenek A, Martina A, Dana K, Tomas B, Lucie K, Marta K, Jaroslav M, Miroslav P, Jiri V, Roman H.
Eur J Haematol. 2009 Dec 10. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20015241
The authors evaluate association between therapeutic response to bortezomib and thrombospondin and hepatocyte growth factor
(HGF) levels. They find that high pretreatment thrombospondin and low pretreatment HGF concentrations are associated with
therapeutic response to bortezomib in patients with myeloma.
NResearchers debate best use of stem cell transplants in patients with multiple myeloma.
Rowan K.
J Natl Cancer Inst. 2009 Dec 2;101(23):1608-11. [Epub 2009 Nov 12.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19910555
Comment on: J Natl Cancer Inst. 2009 Dec 2;101(23):1610.
NA high-affinity fully human anti-IL-6 mAb, 1339, for the treatment of multiple myeloma.
Fulciniti M, Hideshima T, Vermot-Desroches C, Pozzi S, Nanjappa P, Shen Z, Patel N, Smith ES, Wang W, Prabhala R, Tai YT, Tassone P,
Anderson KC, Munshi NC.
Clin Cancer Res. 2009 Dec 1;15(23):7144-52. [Epub 2009 Nov 24.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19934301
The authors' data confirm in vitro and in vivo anti-multiple myeloma activity of, as well as inhibition of bone turnover by, fully
humanized mAb 1339, as a single agent and in combination with conventional and novel agents (including bortezomib and
lenalidomide), providing a rationale for its clinical evaluation in myeloma.
NInteractions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib.
Ooi MG, Hayden PJ, Kotoula V, McMillin DW, Charalambous E, Daskalaki E, Raje NS, Munshi NC, Chauhan D, Hideshima T, Buon
L, Clynes M, O'Gorman P, Richardson PG, Mitsiades CS, Anderson KC, Mitsiades N.
Clin Cancer Res. 2009 Dec 1;15(23):7153-60. [Epub 2009 Nov 24.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19934289
The authors find that a differential response of myeloma versus epithelial carcinomas to combination of nutlin-3 with bortezomib
sheds new light on the role of p53 in bortezomib-induced apoptosis. Concurrent Hdm2 inhibition with bortezomib may extend the
spectrum of bortezomib applications to malignancies with currently limited sensitivity to single-agent bortezomib or, in the future, to
myeloma patients with decreased clinical responsiveness to bortezomib-based therapy.
NMulticenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple
myeloma.
Richardson PG, Weller E, Jagannath S, Avigan DE, Alsina M, Schlossman RL, Mazumder A, Munshi NC, Ghobrial IM, Doss D, Warren
DL, Lunde LE, McKenney M, Delaney C, Mitsiades CS, Hideshima T, Dalton W, Knight R, Esseltine DL, Anderson KC.
J Clin Oncol. 2009 Dec 1;27(34):5713-9. [Epub 2009 Sep 28.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19786667
This phase I, dose-escalation study evaluates safety and determines the maximum-tolerated dose of lenalidomide plus bortezomib in
patients with relapsed or with relapsed and refractory myeloma.
NPrognostic significance of apoptotic index in multiple myeloma patients treated by conventional therapy and novel agents,
thalidomide and bortezomib.
Minarik J, Scudla V, Ordeltova M, Bacovsky J, Pika T, Langova K.
Eur J Haematol. 2009 Dec 1;83(6):528-34. [Epub 2009 Jul 18.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19624720
The authors seek to assess the outcome of the measurement of apoptotic index in myeloma patients treated by conventional
chemotherapy and novel drugs (including thalidomide and bortezomib). Their results suggest the use of apoptotic index by flow
cytometry measurement as a fast and accessible method for prognostic stratification of myeloma patients in routine practice.
www.myeloma.org
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NThe proteasome inhibitor CEP-18770 enhances the anti-myeloma activity of bortezomib and melphalan.
Sanchez E, Li M, Steinberg JA, Wang C, Shen J, Bonavida B, Li ZW, Chen H, Berenson JR.
Br J Haematol. 2009 Dec 1. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19958357
These studies provide strong preclinical rationale for further development of the proteasome inhibitor CEP-18770 in the treatment of
myeloma as a monotherapy, as well as combined with either melphalan or bortezomib.
NRelapse/Refractory myeloma patient: potential treatment guidelines.
San Miguel JF.
J Clin Oncol. 2009 Dec 1;27(34):5676-7. [Epub 2009 Sep 28.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19786652
Comment on: J Clin Oncol. 2009 Dec 1;27(34):5713-9.
NBortezomib-based therapy as induction regimen of an autograft program in front-line treatment of multiple myeloma with
end-stage renal disease.
Siniscalchi A, Dentamaro T, Perrotti A, Tatangelo P, de Fabritiis P, Caravita T.
Ann Hematol. 2009 Dec 2. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19953253
No abstract available.
NBortezomib in combination with dexamethasone and subsequent thalidomide for newly-diagnosed multiple myeloma: a
Chinese experience.
Zheng W, Wei G, Ye X, He J, Li L, Wu W, Shi J, Zhang J, Huang W, Xie W, Luo Y, Xue X, Lin M, Huang H, Cai Z.
Leuk Res. 2009 Dec;33(12):1615-8.
:
http://www.ncbi.nlm.nih.gov/pubmed/19773080
The authors' preliminary experience in Chinese patients indicates that bortezomib-dexamethasone-thalidomide is highly effective
in newly-diagnosed myeloma. The relative lower rates of neuropathy and DVT/PE in the Chinese patients with myeloma are being
cautiously observed.
NCombined effects of bortezomib and daunorubicin on multiple myeloma cell KM3 in vitro.
Ouyang GF, Lin MF.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Dec;17(6):1468-71.
:
http://www.ncbi.nlm.nih.gov/pubmed/20030928
This study finds that bortezomib has synergistic inhibitory effect with daunorubicin on the growth of human myeloma cell line KM3
cell in vitro.
NHematology: first-line bortezomib benefits patients with multiple myeloma.
Dimopoulos MA, Terpos E.
Nat Rev Clin Oncol. 2009 Dec;6(12):683-5.
:
http://www.ncbi.nlm.nih.gov/pubmed/19942924
Comment on: J Clin Oncol. 2009 Jul 20;27(21):3518-25.
NIn vitro anti-myeloma activity of the Aurora kinase inhibitor VE-465.
Negri JM, McMillin DW, Delmore J, Mitsiades N, Hayden P, Klippel S, Hideshima T, Chauhan D, Munshi NC, Buser CA, Pollard J,
Richardson PG, Anderson KC, Mitsiades CS.
Br J Haematol. 2009 Dec;147(5):672-6. [Epub 2009 Sep 14.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19751238
This study characterizes the preclinical anti-myeloma activity of VE465 and finds that combination with bortezomib finds no
antagonism.
www.myeloma.org
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NLong-term outcomes of autologous transplantation in multiple myeloma: significant survival benefit of novel drugs in post-
transplantation relapse.
Krejci M, Scudla V, Tothova E, Schutzova M, Koza V, Adam Z, Krivanova A, Pour L, Buchler T, Sandecka V, Kralova D, Zahradova L,
Vorlicek J, Mayer J, Hajek R.
Clin Lymphoma Myeloma. 2009 Dec;9(6):436-42.
:
http://www.ncbi.nlm.nih.gov/pubmed/19951883
The authors find that the achievement of complete response after transplantation, ISS stage other than III, and administration of
thalidomide or bortezomib in posttransplantation relapse are significant parameters favoring long-term posttransplantation survival for
newly diagnosed myeloma patients.
NRegulatory effect of thalidomide on the expression of constimulatory molecules in patients with multiple myeloma. [Article in
Chinese]
Yang Y, Zhang WG, He AL, Yang HY, Wang Y, Tian W.
Nan Fang Yi Ke Da Xue Xue Bao. 2009 Dec;29(12):2470-2.
:
http://www.ncbi.nlm.nih.gov/pubmed/20034904
This study finds that thalidomide can up-regulate the expression of B7-1 molecules on myeloma cells, which the authors conclude is
probably one of the therapeutic mechanisms of thalidomide.
NThe relationship among tumor architecture, pharmacokinetics, pharmacodynamics, and efficacy of bortezomib in mouse
xenograft models.
Williamson MJ, Silva MD, Terkelsen J, Robertson R, Yu L, Xia C, Hatsis P, Bannerman B, Babcock T, Cao Y, Kupperman E.
Mol Cancer Ther. 2009 Dec;8(12):3234-43.
:
http://www.ncbi.nlm.nih.gov/pubmed/19934276
The authors compare and contrast the differences between a bortezomib-responsive and a bortezomib-resistant models and establish a
relationship among tumor perfusion, drug exposure, pharmacodynamic response and efficacy, and provide an explanation for why some
solid tumor models do not respond to bortezomib treatment.
NRetrospective analysis of 71 cases of multiple myeloma. [Article in Chinese]
Yang P, Zhang WJ, Jing HM, Ke XY.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Dec;17(6):1573-6.
:
http://www.ncbi.nlm.nih.gov/pubmed/20030950
The authors find that a bortezomib-combined regimen may be considered as a new and effective regimen for myeloma patients.
NTreatment of multiple myeloma: 2009 update.
No authors listed.
Prescrire Int. 2009 Dec;18(104):263-6.
:
http://www.ncbi.nlm.nih.gov/pubmed/20025098
This review updates discussions of the use of bortezomib and thalidomide for myeloma patients pre- and post- autologous stem cell
transplantation, as well as the use of lenalidomide in patients who relapse or who are refractory to initial treatment.
NUpdate in multiple myeloma: international criteria for treatment response and renal complications. [Article in French]
Decaux O, Karras A.
Rev Med Interne. 2009 Dec;30(12):1080-3. [Epub 2009 Oct 14.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19833418
No abstract available.
NThe use of novel agents in the treatment of relapsed and refractory multiple myeloma.
Laubach JP, Mahindra A, Mitsiades CS, Schlossman RL, Munshi NC, Ghobrial IM, Carreau N, Hideshima T, Anderson KC, Richardson
PG.
Leukemia. 2009 Dec;23(12):2222-32. [Epub 2009 Sep 10.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19741729
This review focuses on the role of thalidomide, lenalidomide, and bortezomib in relapsed and refractory myeloma.
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