/var/www/vhosts/myeloma.org/httpdocs/spider_articles/pdfs/CitingsThal-Rev-Q1-07

Published by the C
International I
Myel
T
oma Founda
ItionNVOLG
UME IV, ISSUE I S
Q1/2007
ThalidomideandRevlimid®Issue
The International Myeloma Foundation (IMF) is pleased to present our first edition of CITINGS for
2007. This quarterly publication features citations to the most up-to-date studies on myeloma treatment. In
this issue, we focus on thalidomide and Revlimid 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 (2873) or at our website
www.myeloma.org.
Susie Novis, President, IMF
Thalidomide/RevlimidPublications
1stQuarter,2007
NThe combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to
cyclophosphamide vincristine doxorubicin methylprednisolone as induction chemotherapy prior to
autologous transplantation for multiple myeloma: a case-matched analysis.
Wu P, Davies FE, Horton C, Jenner MW, Krishnan B, Alvares CL, Saso R, McCormack R, Dines S, Treleaven JG, Potter MN,
Ethell ME, Morgan GJ.
Leuk Lymphoma. 2006 Nov;47(11):2335-8.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17107906&query_
hl=37&itool=pubmed_DocSum
The authors conduct a retrospective case-matched study and conclude that the oral regimen CTD (cyclophosphamide
thalidomide dexamethasone) may emerge as the superior induction regimen as compared to infusional CVAMP
(cyclophosphamide vincristine doxorubicin methylprednisolone) prior to autologous peripheral blood stem-cell
transplantation.
A retrospective case-matched study was conducted to compare the oral regimen CTD (cyclophosphamide thalidomide dexamethasone)
and infusional CVAMP (cyclophosphamide vincristine doxorubicin methylprednisolone) as induction therapy followed by autologous
peripheral blood stem-cell transplantation (PBSCT) for newly diagnosed multiple myeloma patients. The response rate after three cycles of
treatment was statistically higher with CTD (n = 27) compared to CVAMP (n = 27) (89% vs. 56%, P = 0.016). Toxicity studies showed more
neutropenia (grade 3/4) (4% vs. 60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as
the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability.
www.myeloma.org
(800) 452 - CURE (2873)
Funded by an educational grant from Celgene Corporation.

NThe efficacy of low dose thalidomide in refractory/relapsed myeloma-a retrospective audit.
Cherian G, Thomas DW, Rule SA.
Leuk Lymphoma. 2006 Nov;47(11):2409-11.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17107918&query_
hl=37&itool=pubmed_DocSum
No abstract available.
NMyeloma, thalidomide and thrombosis.
Honemann D, Prince HM.
Leuk Lymphoma. 2006 Nov;47(11):2273-5.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17107896&query_
hl=37&itool=pubmed_DocSum
No abstract available.
NProspective evaluation of low-dose warfarin for prevention of thalidomide associated venous
thromboembolism.
Miller KC, Padmanabhan S, Dimicelli L, Depaolo D, Landrigan B, Yu J, Doran V, Marshal P, Chanan-Khan A.
Leuk Lymphoma. 2006 Nov;47(11):2339-43.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17107907&query_
hl=37&itool=pubmed_DocSum
The authors find that low-dose warafin decreases the incidence of venous thromboemobolism in thalidomide-based chemotherapy
regimens.
Venous thromboemobolism (VTE) is an important complication of thalidomide therapy especially when it is combined with steroids or
chemotherapy. Currently there is no consensus on the most appropriate prophylactic approach. We prospectively investigated the use of low-
dose warfarin sodium in prevention of thalidomide-associated VTE in patients receiving thalidomide-based combination therapies. Patients
with multiple myeloma or chronic lymphocytic leukemia who were treated on thalidomide based-combination therapies were treated on
low-dose warfarin (1 or 2 mg) continuously through the duration of their therapy. Among the 68 patients enrolled, four developed an
episode of VTE, an overall incidence of 5.9% (odds = 0.063). Median duration of thalidomide therapy was 4 months. Low-does warfarin
decreases the incidence of VTE compared to historical control and is an effective mechanism of prevention of VTE in thalidomide-based
chemotherapy regimens.
NCurrent status of new drugs for the treatment of patients with multiple myeloma.
Kenealy M, Prince HM.
Intern Med J. 2006 Dec;36(12):781-9.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17096741&query_
hl=37&itool=pubmed_DocSum
This review focuses on the use of thalidomide, lenalidomide and bortezomib in the treatment of myeloma, presenting current
clinical experience with respect to efficacy and toxicity of these agents.
Multiple myeloma, a malignant disorder of plasma cells, is the second most common haematological malignancy. Although treatable,
multiple myeloma remains incurable in virtually all cases, with a median survival of 3-4 years. Fortunately for patients with this disease,
traditional treatment paradigms have been challenged with the emergence of a number of new therapies entering clinical practice over the
last 6 years. In this review, we focus on the use of thalidomide (Thalidomide Pharmion; Boulder, CO, USA), lenalidomide (Revlimid; Celgene
Corporation, Summit, NJ, USA) and bortezomib (Velcade; Janssen Pharmaceutica N.V., Belgium) in the treatment of myeloma. We present
the current clinical experience with respect to efficacy and toxicity of these promising new agents and how the incorporation of these drugs
with traditional therapies may improve the outcome for patients with multiple myeloma.
www.myeloma.org
(800) 452 - CURE (2873)

NThe troublesome toxicity of peripheral neuropathy with thalidomide.
Mileshkin L, Prince HM.
Leuk Lymphoma. 2006 Nov;47(11):2276-9.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17107897&query_
hl=37&itool=pubmed_DocSum
No abstract available.
NPhase I trial of three-weekly Docetaxel, Carboplatin and oral lenalidomide (Revlimid(R)) in patients
with advanced solid tumors.
Kalmadi S, Davis M, Dowlati A, O'keefe S, Cline-Burkhardt M, Pelley RJ, Borden E, Dreicer R, Bukowski R, Mekhail T.
Invest New Drugs. 2006 Nov 11; [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17103043&query_
hl=37&itool=pubmed_DocSum
This study seeks to determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral
lenalidomide.
Introduction: Lenalidomide is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and a different
toxicity profile. In preclinical trials it has shown synergy with chemotherapy. Patients and methods: Primary objective of this study was to
determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral lenalidomide in a standard phase I study
design. Between September 2004 and May 2005, 14 patients with pathologically proven solid tumors, </=2 prior chemotherapy regimens,
performance status ECOG 0/1, and adequate organ function were enrolled. Dose limiting toxicities (DLT) were defined as >/= grade 3
non-hematological, or grade 4 hematological toxicity. No growth factors were used during cycle 1. Results: Three of four patients treated
at dose level 1, docetaxel 60 mg/m2 and carboplatin AUC 6 on Day 1, and lenalidomide 10 mg orally daily on Days 1-14 of a 21 day cycle
experienced DLT (grade 3 electrolyte changes in two patients, and grade 4 neutropenia in one patient). Ten patients were treated at dose
level -1, docetaxel 60 mg/m2 and carboplatin AUC 6 on Day 1, and lenalidomide 5 mg orally daily on Days 1-14 of a 21 day cycle with one
DLT (Grade 4 neutropenia). There were no treatment-related deaths or irreversible toxicities. Of the 14 response-evaluable patients, five
achieved a partial response (5 out of 9 patients with non-small cell lung cancer. Conclusions: Docetaxel 60 mg/m2 and carboplatin AUC
6 on Day 1, with lenalidomide 5 mg orally daily on Days 1-14 days of a 21 day cycle is the maximum tolerated dose without the use of
prophylactic growth factors. This combination is active and further evaluation in a phase II trial is warranted.
NMaintenance therapy with thalidomide improves survival in patients with multiple myeloma.
Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Agha IY, Bourhis JH, Garderet L, Pegourie B,
Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P,
Facon T; Inter-Groupe Francophone du Myelome (IFM).
Blood. 2006 Nov 15;108(10):3289-94. [Epub 2006 Jul 27.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16873668&query_
hl=37&itool=pubmed_DocSum
This study concludes that thalidomide is an effective maintenance therapy in patients with myeloma, whereas maintenance
treatment with pamidronate does not decrease the incidence of bone events.
Newer chemotherapeutic protocols as well as high-dose chemotherapy have increased the response rate in myeloma. However, these
treatments are not curative. Effective maintenance strategies are now required to prolong the duration of response. We conducted a
randomized trial of maintenance treatment with thalidomide and pamidronate. Two months after high-dose therapy, 597 patients younger
than age 65 years were randomly assigned to receive no maintenance (arm A), pamidronate (arm B), or pamidronate plus thalidomide
(arm C). A complete or very good partial response was achieved by 55% of patients in arm A, 57% in arm B, and 67% in arm C (P = .03).
The 3-year postrandomization probability of event-free survival was 36% in arm A, 37% in arm B, and 52% in arm C (P < .009). The 4-year
postdiagnosis probability of survival was 77% in arm A, 74% in arm B, and 87% in arm C (P < .04). The proportion of patients who had
skeletal events was 24% in arm A, 21% in arm B, and 18% in arm C (P = .4). Thalidomide is an effective maintenance therapy in patients
with multiple myeloma. Maintenance treatment with pamidronate does not decrease the incidence of bone events.
www.myeloma.org
(800) 452 - CURE (2873)

NA randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and
refractory multiple myeloma.
Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, Schlossman RL, Rajkumar SV, Desikan KR,
Hideshima T, Munshi NC, Kelly-Colson K, Doss D, McKenney ML, Gorelik S, Warren D, Freeman A, Rich R, Wu A, Olesnyckyj M, Wride K,
Dalton WS, Zeldis J, Knight R, Weller E, Anderson KC.
Blood. 2006 Nov 15;108(10):3458-64. [Epub 2006 Jul 13.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16840727&query_
hl=54&itool=pubmed_DocSum
This study finds lenalidomide to be active and well tolerated in relapsed, refractory myeloma, with a 30-mg once-daily regiment
providing a basis for future studies as monotherapy and in combination with dexamethasone.
This multicenter, open-label, randomized phase 2 study evaluated 2 dose regimens of lenalidomide for relapsed, refractory
myeloma. Seventy patients were randomized to receive either 30 mg once-daily or 15 mg twice-daily oral lenalidomide for 21
days of every 28-day cycle. Patients with progressive or stable disease after 2 cycles received dexamethasone. Analysis of the first
70 patients showed increased grade 3/4 myelo-suppression in patients receiving 15 mg twice daily (41% versus 13%, P = .03).
An additional 32 patients received 30 mg once daily. Responses were evaluated according to European Group for Blood and
Marrow Transplantation (EBMT) criteria. Overall response rate (complete, partial, or minor) to lenalidomide alone was 25%
(24% for once-daily and 29% for twice-daily lenalidomide). Median overall survival in 30-mg once-daily and twice-daily groups
was 28 and 27 months, respectively. Median progression-free survival was 7.7 months on once-daily versus 3.9 months on twice-
daily lenalidomide (P = .2). Dexamethasone was added in 68 patients and 29% responded. Time to first occurrence of clinically
significant grade 3/4 myelosuppression was shorter in the twice-daily group (1.8 vs 5.5 months, P = .05). Significant peripheral
neuropathy and deep vein thrombosis each occurred in only 3%. Lenalidomide is active and well tolerated in relapsed, refractory
myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone.
NLenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory
multiple myeloma: safety and efficacy.
Baz R, Walker E, Karam M, Choueiri T, Jawde R, Bruening K, Reed J, Faiman B, Ellis Y, Brand C, Srkalovic G, Andresen S,
Knight R, Zeldis J, Hussein M.
Ann Oncol. 2006 Dec;17(12):1766-71. [Epub 2006 Sep 15.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16980599&query_
hl=54&itool=pubmed_DocSum
The authors conduct a phase I/II trial of the combination of lenalidomide and chemotherapy. They find it to be well tolerated,
resulting in high response rates in their mostly refractory myeloma patient population.
BACKGROUND: Lenalidomide is active and well tolerated in relapsed and refractory multiple myeloma. We conducted a phase I/II trial of
the combination of lenalidomide and chemotherapy to evaluate the safety and efficacy of the combination. METHODS: The 62 patients
enrolled received liposomal doxorubicin 40 mg/m2 i.v. and vincristine 2 mg i.v. on day 1, dexamethasone 40 mg p.o. on days 1-4 (DVd),
and lenalidomide on days 1-21 in 28-day cycles. Primary end points were maximum tolerated dose (MTD) of lenalidomide with DVd
chemotherapy and overall response rate (ORR) by Southwest Oncology Group criteria of the combination. Findings: The median age was 62
years, 70% of patients were males and 65% had refractory multiple myeloma. The MTD of lenalidomide with DVd chemotherapy was 10 mg
and the dose-limiting toxicity was non-neutropenic sepsis. After 7.5 months of median follow-up, the ORR of the combination was 75%, with
29% of patients achieving a complete or near complete remission. The median progression-free survival was 12 months, while the median
overall survival has not yet been reached. Interpretation: The combination of lenalidomide and DVd chemotherapy was well tolerated and
resulted in high response rates in this mostly refractory patient population. Evaluation of this combination in newly diagnosed patients is
warranted.
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 Feb 15; [Epub ahead of print.]
:
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.
www.myeloma.org
(800) 452 - CURE (2873)

NLong-term results of thalidomide in refractory and relapsed multiple myeloma with emphasis on response
duration.
Cibeira MT, Rosinol L, Ramiro L, Esteve J, Torrebadell M, Blade J.
Eur J Haematol. 2006 Dec;77(6):486-92. [Epub 2006 Sep 15.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16978238&query_
hl=37&itool=pubmed_DocSum
The authors the quality and duration of thalidomide when administered as a single agent in patients with refractory or relapsed
multiple myeloma, and find that the effect of thalidomide can be sustained, particularly in patients who achieve a greater degree
of response.
Objective: Thalidomide administered as a single agent produces a response rate of about 40% in patients with refractory or relapsed
multiple myeloma (MM). The aim of our study was to determine the quality and duration of such responses. Patients and methods: Forty-
two consecutive patients with refractory (20) or relapsed (22) MM were given thalidomide as a single agent at our institution. Most of them
(70%) had previously received two or more lines of therapy, and 38% had undergone autologous stem cell transplantation. Results: Eighteen
patients (43%) responded to thalidomide [11 minimal responses (MR) and seven partial responses (PR)] according to the European Marrow
Transplant Registry (EBMT) criteria. The median time to response was 3 months and the median duration of therapy in responding patients
was 9 months. Treatment was discontinued because of toxicity in 10 responding patients. The toxicity mainly led to peripheral neuropathy
and fatigue. At the time of this analysis, all responding patients had progressed except one who remains in continued stable PR. The median
time to progression was 15.6 months (range 1.3 to 70+), with a trend towards a longer duration for patients who achieved PR vs. MR (21.2
vs. 11.2 months, P = 0.11). The median duration of response was 12.4 months (range: 0.3-67+) (17.2 months for PR vs. 9.7 months for MR,
P = 0.11). Conclusion: These results show that the effect of thalidomide in refractory/relapsed MM can be sustained, particularly in patients
who achieve a greater degree of response, and support the finding that this drug can be used for maintenance therapy.
NThalidomide and lenalidomide in multiple myeloma.
Mazumder A, Jagannath S.
Best Pract Res Clin Haematol. 2006 Dec;19(4):769-80.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16997182&query_
hl=1&itool=pubmed_DocSum
The authors discuss the promising results of thalidomide and lenalidomide as single agents and in combination with
glucocorticoids for the treatment of chemotherapy-refractory myeloma.
Multiple myeloma is a treatable but not necessarily a curable plasma-cell cancer. After decades of minimal progress, two new classes of drugs
with novel mechanisms of action immunomodulatory drugs (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib)
have been introduced for the treatment of this disease. Thalidomide and lenalidomide have shown great activity as single agents and in
combination with glucocorticoids for the treatment of chemotherapy-refractory myeloma. Thalidomide and more recently lenalidomide
in combination with dexamethasone have shown promising results as induction therapy. These drugs can easily be combined with
other chemotherapeutic agents to potentiate the anti-myeloma effect. The immunomodulatory function of these drugs can be successfully
exploited to control residual disease during remission. Thus, both thalidomide and lenalidomide have ushered in a new era of optimism in
the management of this incurable cancer.
NOsteonecrosis of the jaws in newly diagnosed multiple myeloma patients treated with zoledronic acid and
thalidomide-dexamethasone.
Tosi P, Zamagni E, Cangini D, Tacchetti P, Di Raimondo F, Catalano L, D'Arco A, Ronconi S, Cellini C, Offidani M, Perrone G,
Ceccolini M, Brioli A, Tura S, Baccarani M, Cavo M.
Blood. 2006 Dec 1;108(12):3951-2.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17114572&query_
hl=37&itool=pubmed_DocSum
No abstract available.
www.myeloma.org
(800) 452 - CURE (2873)

NBortezomib, melphalan, prednisone and thalidomide for relapsed multiple myeloma.
Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V, Cangialosi C, Caravita T, Morabito F, Musto P,
Bringhen S, Falco P, Avonto I, Cavallo F, Boccadoro M.
Blood. 2006 Dec 5; [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17148584&query_
hl=37&itool=pubmed_DocSum
This phase I/II trial seeks to determine the dosing, safety, and efficacy of the 4-drug combination of bortezomib ( Velcade),
melphalan, prednisone, and thalidomide ( VMPT). The authors conclude that VMPT is an effective salvage therapy with a very
high proportion of responses and unexpectedly low incidences of neurotoxicity.
In multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly
increased response rate and event-free survival. In this multicenter phase I/II trial, dosing, safety, and efficacy of the 4-drug combination,
bortezomib (VELCADE(R)), melphalan, prednisone and thalidomide (VMPT) was determined. Bortezomib was administered at three dose
levels (1.0 mg/m2, 1.3 mg/m2 or 1.6 mg/m2) on days 1, 4, 15, 22; melphalan at 6 mg/m2 on days 1-5, prednisone at 60 mg/m2 on days 1-5.
Thalidomide was delivered at 50 mg on days 1-35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was
1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled: 20 patients (67%) achieved a partial response (PR) including 13
patients (43%) who achieved at least a very good partial response. Among 14 patients who received VMPT as second-line treatment, the PR
rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year
survival from study entry was 84%. Grade 3 nonhematologic adverse events included: infections (5 patients), fatigue (1), vasculitis (1) and
peripheral neuropathy (2), no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very
high proportion of responses. The incidence of neurotoxicities was unexpectedly low.
NThalidomide- and lenalidomide-associated thromboembolism among patients with cancer.
Bennett CL, Angelotta C, Yarnold PR, Evens AM, Zonder JA, Raisch DW, Richardson P.
JAMA. 2006 Dec 6;296(21):2558-60.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17148721&query_
hl=37&itool=pubmed_DocSum
No abstract available.
NCurrent and emerging views and treatments of systemic immunoglobulin light-chain (Al) amyloidosis.
Comenzo RL.
Contrib Nephrol. 2007;153:195-210.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17075231&query_
hl=3&itool=pubmed_DocSum
The author discusses the latest treatments for amyloidosis, including the use of thalidomide, bortezomib, and lenalidomide, all
novel therapies currently under study.
Amyloidosis is a disease in which abnormal proteins form toxic intermediates and fibrillar tissue-deposits that compromise key viscera and
lead to early death. In order to treat amyloidosis, the type of abnormal protein must be identified. The most common type is monoclonal
immunoglobulin light chain or AL amyloidosis. One-third to one-half of patients with systemic AL amyloidosis has renal involvement in
the form of glomerular, vascular and interstitial deposits of amyloid causing progressive proteinuria. Less than 5% of AL patients present
with renal failure requiring dialysis; patients with renal involvement usually present with fatigue, peripheral edema, proteinuria and
hypoalbuminemia. The aim of therapy in systemic AL amyloidosis is to reduce the amyloid-forming monoclonal light chains, measured with
the serum free light chain assay, by suppressing the underlying plasma cell dyscrasia, while using supportive measures to sustain organ
function. Amyloid deposits can be resorbed and organ function restored if the amyloid-forming precursor light chain is eliminated. The most
effective treatment for systemic AL is risk-adapted melphalan with peripheral blood stem cell transplant; oral melphalan and dexamethasone
is the most effective therapy for patients who are not stem cell transplant candidates although it carries a risk of myelodysplasia and
leukemia. Novel therapies currently under study include thalidomide, bortezomib and lenalidomide. With therapy, a majority of patients
can achieve long-term durable remissions with stabilization or recovery of organ function. The use of novel antibody-based approaches for
imaging amyloid and possibly for accelerating removal of deposits is under active investigation.
www.myeloma.org
(800) 452 - CURE (2873)

NFinal Report of Toxicity and Efficacy of a Phase II Study of Oral Cyclophosphamide, Thalidomide, and
Prednisone for Patients with Relapsed or Refractory Multiple Myeloma: A Hoosier Oncology Group
Trial, HEM01-21.
Suvannasankha A, Fausel C, Juliar BE, Yiannoutsos CT, Fisher WB, Ansari RH, Wood LL, Smith GG, Cripe LD, Abonour R.
Oncologist. 2007 Jan;12(1):99-106.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17227904&query_
hl=1&itool=pubmed_DocSum
The Hoosier Oncolog y Group conducts a phase II trial of oral cyclophosphamide, thalidomide, and prednisone in the treatment
of patients with relapsed or refractory multiple myeloma (MM) and finds that the efficacy and low toxicity of the regiment support
the future development of such an approach to MM.
Thalidomide has direct antimyeloma and immunomodulatory effects. In addition, both thalidomide and metronomic chemotherapy inhibit
angiogenesis. The synergy of such a combination may decrease toxicity while maintaining efficacy. The Hoosier Oncology Group conducted
a phase II trial of oral cyclophosphamide (50 mg b.i.d. for 21 days), thalidomide (200 mg/day), and prednisone (50 mg q.o.d.) (CTP) per
28-day course in patients with relapsed multiple myeloma (MM). Of the 37 patients enrolled, 16 had prior stem cell transplantation. The
median follow-up time was 25.3 months (95% confidence interval [CI] 23.2-27.7). Of 35 patients treated, 22 patients (62.9%) responded: 7
(20.0%) complete responses, 2 (5.7%) near-complete responses, and 13 (37.1%) partial responses. Eight patients (22.9%) had stable disease,
and three (8.6%) had disease progression. Two patients withdrew from the study early due to reasons unrelated to progression or toxicity
and were treated as nonresponders. The median time to best response and time to progression were 3.6 months (95% CI 2.8-10.9) and
13.2 months (95% CI 9.4-21.0), respectively. The median number of treatment cycles was seven (range 1-12 cycles). Grade III to IV toxicities
included leukopenia (42.9%; febrile neutropenia, 11.4%), hyperglycemia (20%), sensory neuropathy (11.4%), thromboses (8%), and motor
neuropathy (5.7%). No patient withdrew from the study due to toxicity. The efficacy and low toxicity of the CTP regimen support the future
development of such an approach in MM.
NThalidomide and celecoxib as potential modulators of irinotecan's activity in cancer patients.
Villalona-Calero M, Schaaf L, Phillips G, Otterson G, Panico K, Duan W, Kleiber B,
Shah M, Young D, Wu WH, Kuhn J.
Cancer Chemother Pharmacol. 2007 Jan;59(1):23-33. [Epub 2006 May 10.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16685529&query_
hl=37&itool=pubmed_DocSum
The authors test the feasibility of combining irinotecan with thalidomide in patients with refractory malignancies and conclude
that the combination of thalidomide/irinotecan is safe and devoid of PK interactions.
PURPOSE: Nuclear factor-kappaB (NF-kappaB) activation induces resistance to irinotecan. Preclinically, thalidomide and COX-2 inhibitors
reduce NF-kappaB activation. We tested the feasibility of combining irinotecan with thalidomide and thalidomide/celecoxib in patients with
refractory malignancies. PATIENTS/METHODS: The study was conducted in two parts. First, the optimal dose of thalidomide (400 or 200
mg daily) in combination with irinotecan 125 mg/m2 days 1 and 8 every 3 weeks was determined. In the second part, celecoxib 400 mg
twice-daily was added to irinotecan/thalidomide. Pharmacokinetics of irinotecan and thalidomide alone or concurrently were evaluated.
Tumor necrosis factor alpha, beta-fibroblast growth factor, and NF-kappaB activation were measured in blood mononuclear cells (PBMC).
No CYP450 enzyme inducers/inhibitors were allowed. RESULTS: Thirty-six patients were enrolled: Eleven received thalidomide 400 mg, 13
thalidomide 200 mg and 12 thalidomide 400 mg and celecoxib, with irinotecan. For the two-drug combination, there was a higher rate of
moderate/severe diarrhea/myelosuppression with thalidomide 200 mg. Thus thalidomide 400 mg was combined with celecoxib. The triple
combination resulted in similar toxicity as the doublet with the lower thalidomide dose. Concurrent administration of irinotecan/thalidomide
did not influence pharmacokinetics. Anti-tumor responses occurred in two patients and prolonged stabilization in eight others. NF-kappaB
activation increased over time. Patients experiencing tumor response or prolonged stabilization had lower NF-kappaB activation, albeit
not statistically significant (P = 0.124). CONCLUSIONS: The combination of thalidomide/irinotecan is safe and devoid of PK interactions.
Thalidomide 400 mg appeared more suitable for combination, whereas the addition of celecoxib did not improve tolerability. Tumor-specific
studies in patients with lesser prior treatment will be necessary to establish the therapeutic impact of the combinations.
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(800) 452 - CURE (2873)

NThe activity of lenalidomide with or without dexamethasone in patients with primary systemic
amyloidosis.
Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR,
Russell SJ, Kabat B, Gertz MA.
Blood. 2007 Jan 15;109(2):465-70. [Epub 2006 Sep 28.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17008538&query_
hl=11&itool=pubmed_DocSum
The authors study the toxicity and efficacy of lenalidomide in patients with amyloidosis and find limited activity of single-agent
lenalidomide but significant activity of the combination with dexamethasone, warranting further investigation.
Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, is
highly active in patients with multiple myeloma. We studied the toxicity and efficacy of lenalidomide in patients with AL. Patients with
symptomatic AL, a measurable plasma cell disorder, and adequate hematologic and renal reserve were eligible. Patients received single-agent
lenalidomide. If there was no evidence of progression after 3 months or of hematologic response after 3 cycles, dexamethasone was added.
Twenty-three patients were enrolled. Thirteen were previously treated. Organ involvement was cardiac (64%), renal (73%), hepatic (23%),
and nerve (14%). Within the first 3 cycles of therapy, 10 patients discontinued treatment: 4 early deaths, 3 adverse events, and 3 other
causes. With a median follow-up of 17 months, 10 patients responded to treatment. In these patients, responses included 9 hematologic,
4 renal, 2 cardiac, and 2 hepatic. All but one of the responders had dexamethasone added to their treatment program. The most common
grade 3 or 4 adverse events at least possibly attributable to lenalidomide were neutropenia (45%), thrombocytopenia (27%), rash (18%),
and fatigue (18%). In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with
dexamethasone, which warrants further investigation.
NLenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal
CD34+ progenitor cells.
Verhelle D, Corral LG, Wong K, Mueller JH, Moutouh-de Parseval L, Jensen-Pergakes K, Schafer PH, Chen R, Glezer E,
Ferguson GD, Lopez-Girona A, Muller GW, Brady HA, Chan KW.
Cancer Res. 2007 Jan 15;67(2):746-55.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17234786&query_
hl=13&itool=pubmed_DocSum
The authors' results indicate that lenalidomide and CC-4047 have opposite effects in tumor cells versus normal cells and could
explain, at least in part, the reduction of malignant cells and the restoration of bone marrow observed in patients undergoing
lenalidomide treatment. In addition, the authors provide new insights on the cellular pathways affected by lenalidomide and CC-
4047, propose new potential clinical uses, such as bone marrow regeneration, and suggest that the combination of lenalidomide
or CC-4047 with certain HDAC inhibitors may elevate the therapeutic index in the treatment of hematologic malignancies.
Clinical studies involving patients with myelodysplastic syndromes or multiple myeloma have shown the efficacy of lenalidomide by reducing
and often eliminating malignant cells while restoring the bone marrow function. To better understand these clinical observations, we
investigated and compared the effects of lenalidomide and a structurally related analogue, CC-4047, on the proliferation of two different
human hematopoietic cell models: the Namalwa cancer cell line and normal CD34+ progenitor cells. Both compounds had antiproliferative
effects on Namalwa cells and pro-proliferative effects on CD34+ cells, whereas p21WAF-1 expression was up-regulated in both cell types.
In Namalwa cells, the up-regulation of p21WAF-1 correlated well with the inhibition of cyclin-dependent kinase (CDK) 2, CDK4, and CDK6
activity leading to pRb hypophosphorylation and cell cycle arrest, whereas in CD34+ progenitor cells the increase of p21WAF-1 did not
inhibit proliferation. Similarly, antiproliferation results were observed in two B lymphoma cell lines (LP-1 and U266) but interestingly not
in normal B cells where a protection of apoptosis was found. Finally, CC-4047 and lenalidomide had synergistic effects with valproic acid
[a histone deacetylase (HDAC) inhibitor] by increasing the apoptosis of Namalwa cells and enhancing CD34+ cell expansion. Our results
indicate that lenalidomide and CC-4047 have opposite effects in tumor cells versus normal cells and could explain, at least in part, the
reduction of malignant cells and the restoration of bone marrow observed in patients undergoing lenalidomide treatment. Moreover, this
study provides new insights on the cellular pathways affected by lenalidomide and CC-4047, proposes new potential clinical uses, such as
bone marrow regeneration, and suggests that the combination of lenalidomide or CC-4047 with certain HDAC inhibitors may elevate the
therapeutic index in the treatment of hematologic malignancies.
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(800) 452 - CURE (2873)

NLenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial.
Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB, Skinner M, Seldin DC.
Blood. 2007 Jan 15;109(2):492-6. [Epub 2006 Sep 7.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16960148&query_
hl=1&itool=pubmed_DocSum
The authors describe the results of a phase 2 trial of the use of lenalidomide, as a single agent and in combination with
dexamethasone, for the treatment of AL amyloidosis and conclude that the findings from this trial indicate that lenalidomide can
be effective in treating AL amyloidosis.
In immunoglobulin light chain (AL) amyloidosis, amyloid fibril deposits derived from immunoglobulin light chains produced by a clonal
plasma cell dyscrasia accumulate in tissues and damage vital organs. Treatment regimens used in multiple myeloma can be effective in AL
amyloidosis; however, patients with this disease often tolerate these regimens poorly because of multisystem organ dysfunction. Thalidomide
and lenalidomide have both been shown to be effective in myeloma. In this report, we describe results of a phase 2 trial of the use of
lenalidomide, as a single agent and in combination with dexamethasone, for the treatment of AL amyloidosis. Thirty-four patients with AL
amyloidosis, most with prior therapies, were enrolled in the trial. The initial dose of lenalidomide used (25 mg/d) was poorly tolerated;
however, a reduced dose of 15 mg/d was generally well tolerated. Of 24 evaluable patients, 7 (29%) achieved a hematologic complete
response and 9 (38%) achieved a partial hematologic response, for an overall hematologic response rate of 67%. Hematologic responses
were also associated with clinical responses. Fatigue and myelosuppression were the most common treatment-related adverse events (35%),
while thromboembolic complications (9%) were the most serious. Findings from this trial indicate that lenalidomide can be effective in
treating AL amyloidosis.
NSafety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL
amyloidosis.
Wechalekar AD, Goodman HJ, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD.
Blood. 2007 Jan 15;109(2):457-64. [Epub 2006 Sep 21.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16990593&query_
hl=1&itool=pubmed_DocSum
The authors report the use of a risk-adapted oral regimen of cyclophosphamide, thalidomide, and dexamethasone (CTD) or
attenuated CTD (CTDa) in 75 patients with advanced systemic light-chain (AL) amyloidosis. They note that the clonal response
rates to CTD in this study are higher than any previously reported nontransplantation regimen in AL amyloidosis and that risk
adaptation allows its use in poorer risk patients. They conclude that CTD merits prospective randomized study.
High-dose melphalan with stem-cell transplantation is believed to be the most effective treatment for systemic light-chain (AL) amyloidosis,
but many patients are ineligible because of the extent of their disease, and treatment-related mortality (TRM) remains substantial. We report
the use of a risk-adapted oral regimen of cyclophosphamide, thalidomide, and dexamethasone (CTD) or attenuated CTD (CTDa) in 75
patients with advanced AL amyloidosis, including 44 patients with clonal relapse after prior therapy. Fifty-one (68%) patients received CTD
and 24 (32%) received CTDa. A hematologic response occurred in 48 (74%) of 65 evaluable patients, including complete responses in 14
(21%) and partial responses in 34 (53%) cases. Median estimated overall survival (OS) from commencement of treatment was 41 months,
and from diagnosis median was not reached with a median follow-up of 22 months. Three-year estimated OS was 100% and 82% among
complete and partial hematologic responders, respectively. Toxicity necessitating cessation of therapy occurred in 8% and was at least grade 2
in 52% of patients. TRM was 4%. The clonal response rates to CTD reported here are higher than any previously reported nontransplantation
regimen in AL amyloidosis, and risk adaptation allows its use in poorer risk patients. CTD merits prospective randomized study.
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 Feb 15; [Epub ahead of print.]
:
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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NComplete response in myeloma extends survival without, but not with history of prior monoclonal
gammopathy of undetermined significance or smouldering disease.
Pineda-Roman M, Bolejack V, Arzoumanian V, Anaissie E, van Rhee F, Zangari M, Walker R, Hollmig K, Shaughnessy JD Jr,
Epstein J, Krishna S, Crowley J, Barlogie B.
Br J Haematol. 2007 Feb;136(3):393-9. [Epub 2006 Dec 8.]
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17156398&query_
hl=1&itool=pubmed_DocSum
This study compare clinical characteristics and outcomes of patients with "evolved" MM (E-MM) to those with "unknown" prior
history (U-MM). The authors find that in comparison with U-MM, E-MM evolved from monoclonal monoclonal gammopathy of
undetermined significance or smoldering myeloma was associated with a lower complete response (CR) rate without adversely
affecting survival. In contrast, CR was an independent favorable feature for survival in U-MM.
Complete response (CR) is still considered an important surrogate marker for outcome in multiple myeloma (MM). Long-term survival after
transplantation, however, has been observed in a substantial proportion of patients who never achieved CR. The tandem transplant trial,
Total Therapy 2, enrolled 668 patients, who were randomised up-front to thalidomide (THAL) or no THAL; 56 patients were identified as
having had, for at least 6 months prior to initiation of therapy, monoclonal gammopathy of undetermined significance (MGUS, n = 21),
smouldering MM (SMM, n = 22) or solitary plasmacytoma of bone (SPC, n = 13). The clinical characteristics and outcomes of patients
with such `evolved' MM (E-MM) and of those with `unknown' prior history (U-MM) were compared. Fewer patients with MGUS/SMM-E-MM
had anaemia or renal failure; CR was lower (22% vs. 48%) but 4-year estimates of event-free survival (54% vs. 56% with U-MM) and overall
survival (65% vs. 70% with U-MM) were similar to those with SPC-E-MM or U-MM. In the latter group, achieving CR was associated with
prolonged survival. In comparison with U-MM, E-MM evolved from MGUS/SMM was associated with lower CR rate without adversely affecting
survival. In contrast, CR was an independent favourable feature for survival in U-MM.
NEffectivity of thalidomide and dexamethasone for the treatment of refractory multiple myeloma: a
retrospective study of 36 consecutive cases [Article in Spanish].
Khosravi Shahi P, Diaz Munoz de la Espada VM, Sabin Dominguez P, Encinas Garcia S, Arranz Arija JA, Carrion Galindo JR,
Perez Manga G.
Med Clin (Barc). 2007 Feb 3;128(4):121-4.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17288931&query_
hl=1&itool=pubmed_DocSum
The authors perform a retrospective study of 36 patients with refractory multiple myeloma (MM) treated with thalidomide and
dexamethasone as second line therapy and find that this treatment combination is an effective and safe second line treatment for
refractory MM with manageable toxicity.
BACKGROUND AND OBJECTIVE: Multiple myeloma (MM) is a plasma-cell neoplasm characterized by a monoclonal protein in the serum or
urine. Thalidomide is effective as second line treatment. PATIENTS AND METHOD: We performed a retrospective study of 36 consecutive
patients with refractory MM treated with thalidomide and dexamethasone as second line therapy, with the objective of analyzing the rate of
response (primary end point), progression-free survival (PFS) and toxicity profiles (second end points). RESULTS: In our study the overall
response rate was 55.6%, with a median of PFS of 12.6 months (95% confidence interval: 4-21 months). PFS at 6, 12 and 18 months was
61.11%, 50% and 22.22% respectively. 30.6% of the patients had neuropathy, 11.11% had rash and 5.55% had deep vein thrombosis.
CONCLUSIONS: The combination of thalidomide and dexamethasone is an effective and safe second line treatment for refractory MM, with a
manageable toxicity.
NThalidomide and dexamethasone in the treatment of multiple myeloma: progressing step by step
[Article in Spanish].
Gonzalez Gonzalez BJ, Hernandez Nieto L.
Med Clin (Barc). 2007 Feb 3;128(4):133-4.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17288934&query_
hl=1&itool=pubmed_DocSum
No abstract available.
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(800) 452 - CURE (2873)

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 Feb 5. [Epub ahead of print.]
:
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) or the combination thalidomide-dexamethasone-liposomal peg ylated doxorubicin (ThaDD) and
find that the ThaDD regimen significantly improved response rate and overall survival in comparison with Thal-Dex.
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/m2 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.
NThe evolving role of lenalidomide in the treatment of hematologic malignancies.
Kastritis E, Dimopoulos MA.
Expert Opin Pharmacother. 2007 Mar;8(4):497-509.
:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17309344&query_
hl=1&itool=pubmed_DocSum
This article reviews the data on lenalidomide use in patients with hematologic malignancies, including multiple myeloma.
Lenalidomide is an immunomodulatory drug, structurally related to thalidomide, which has pleotropic activity, including antiangiogenic and
antineoplastic properties. This agent is the product of advances in the understanding of the biology of neoplastic cells, their interaction with
the microenvironment and of the underlying molecular pathways. Lenalidomide has shown significant activity in refractory/resistant multiple
myeloma, and further studies have shown its activity in other hematologic malignancies with some very encouraging results, especially in
subsets of patients with myelodysplastic syndromes. This article reviews the data on lenalidomide use in patients with multiple myeloma, as
well as in myelodysplastic syndromes, chronic lymphocytic leukemia and myelofibrosis with myeloid metaplasia.
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 the role of 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.
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