ミエローマと私

IMF（国際骨髄腫財団）から必見すべき資料が2件でています。

★★★2011年ASHハイライト
ASH 2011 Multiple Myeloma Highlights
http://myeloma.org/pdfs/ASH11-Highlights_c1.pdf

☆★★末梢神経障害のレビュー
Management of treatment-emergent peripheral neuropathy in multiple myeloma
http://myeloma.org/pdfs/ASH11-Highlights_c1.pdf

NCCNガイドラインのワルデンストレーム・マクログロブリン血症が2012年1版に更新されました。

http://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf

主な変更点：
・推奨治療レジメンが増えている（WMLPL-B）。
・奏効判定基準のページが追加された（WMLPL-C）。
・考察で以下が追加された。
-- IgM関連神経障害の治療
-- リツシキマブに耐えられない患者の管理
-- 維持療法
その他諸々の変更が行われています。

ボルテゾミブの皮下投与製剤が米FDAで承認されたことが発表されました。

http://myeloma.org/pdfs/SC_VELCADE_Press_Release.pdf

この承認は、222人のボルテゾミブ未治療のMM再発患者を対象に実施された非劣勢試験の結果が基になっており、奏効率は同等ですが、末梢神経障害がグレード3以上で6％対16％、全グレードで38％対53％と皮下投与の方が有意に少なかったことが注目されています。

アメリカ血液学会（ASH）が毎年1回発行している教育誌Hematologyが公開されました。
内容は専門的ですが貴重な資料です。

目次
Hematology 2011
http://asheducationbook.hematologylibrary.org/content/current

多発性骨髄腫における論争と最新情報
Controversies and Updates in Multiple Myeloma

骨髄腫における治療標的の新たな知見
Kenneth C. Anderson
New Insights into Therapeutic Targets in Myeloma
Hematology 2011 2011:184-190
http://asheducationbook.hematologylibrary.org/content/2011/1/184.full.pdf

多発性骨髄腫における幹細胞移植：現状と将来
Sergio Giralt
Stem Cell Transplantation for Multiple Myeloma: Current and Future Status
Hematology 2011 2011:191-196
http://asheducationbook.hematologylibrary.org/content/2011/1/191.full.pdf

骨髄腫における至適移植前治療と移植後維持療法
Donna E. Reece
Posttransplantation Maintenance Therapy and Optimal Frontline Therapy in Myeloma
Hematology 2011 2011:197-204
http://asheducationbook.hematologylibrary.org/content/2011/1/197.full.pdf

多発性骨髄腫における自家幹細胞移植後のレナリドミドまたはボルテゾミブによる維持療法の有益性と二次原発腫瘍の発症リスク
Emma Scott and Donna Reece
What is the Benefit of Maintenance Therapy with Lenalidomide or Bortezomib after Autologous Stem Cell Transplantation in Multiple Myeloma and What is the Risk of Developing a Secondary Primary Malignancy?
Hematology 2011 2011:205-207
http://asheducationbook.hematologylibrary.org/content/2011/1/205.full.pdf

2001年に私がMMの診断を受けた時、骨髄腫研究会で「私の治療」という報告が公開されていました。今それを眺めてみると、65歳以下ではVAD療法→自家移植、それ以外ではMP療法やROAD療法などの化学療法がメインでした。今ではVAD療法は海外ではほとんど使用されておらず、ほとんどベルケイドやレナリドミドをデキサメタゾンまたはMPと併用したものです。最近では日本でも早期にベルケイドやレナリドミドが使用される例が増えているようです。

さて、米国血液学会（ASH）からも「私の治療法（How I Treat）」 シリーズが出ていますので、ここにまとめておきます。

How I Treat シリーズ
http://bloodjournal.hematologylibrary.org/cgi/collection/how_i_treat

高齢の骨髄腫患者
Jayesh Mehta, Michele Cavo, and Seema Singhal
How I treat elderly patients with myeloma
Blood 2010 116:2215-2223; doi:10.1182/blood-2009-10-163329
http://bloodjournal.hematologylibrary.org/content/116/13/2215.full
http://bloodjournal.hematologylibrary.org/content/116/13/2215.full.pdf

若年の骨髄腫患者
A. Keith Stewart, Paul G. Richardson, and Jesus F. San-Miguel
How I treat multiple myeloma in younger patients
Blood 2009 114:5436-5443; doi:10.1182/blood-2009-07-204651
http://bloodjournal.hematologylibrary.org/content/114/27/5436.full.pdf

アミロイドーシス
Raymond L. Comenzo
How I treat amyloidosis
Blood 2009 114:3147-3157; doi:10.1182/blood-2009-04-202879
http://bloodjournal.hematologylibrary.org/content/114/15/3147.full.pdf

ワルデンストレーム・マクログロブリン血症
Steven P. Treon
How I treat Waldenstrom macroglobulinemia
Blood 2009 114:2375-2385; doi:10.1182/blood-2009-05-174359
http://bloodjournal.hematologylibrary.org/content/114/12/2375.full.pdf

血液疾患患者のインフルエンザ
Corey Casper, Janet Englund, and Michael Boeckh
How I treat influenza in patients with hematologic malignancies
Blood 2010 115:1331-1342; doi:10.1182/blood-2009-11-255455
http://bloodjournal.hematologylibrary.org/content/115/7/1331.full.pdf

同種移植後の晩期障害
Bipin N. Savani, Michelle L. Griffith, Shubhada Jagasia, and Stephanie J. Lee
How I treat late effects in adults after allogeneic stem cell transplantation
Blood 2011 117:3002-3009; doi:10.1182/blood-2010-10-263095
http://bloodjournal.hematologylibrary.org/content/117/11/3002.full.pdf

GVHDの総合評価
Paul A. Carpenter
How I conduct a comprehensive chronic graft-versus-host disease assessment
Blood 2011 118:2679-2687; doi:10.1182/blood-2011-04-314815
http://bloodjournal.hematologylibrary.org/content/118/10/2679.full.pdf

造血幹細胞採取困難例
L. Bik To, Jean-Pierre Levesque, and Kirsten E. Herbert
How I treat patients who mobilize hematopoietic stem cells poorly
Blood 2011 118:4530-4540; doi:10.1182/blood-2011-06-318220
http://bloodjournal.hematologylibrary.org/content/118/17/4530.full.pdf

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◆試験I
http://ash.confex.com/ash/2011/webprogram/Session3598.html
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475：導入療法；レナリドミド・メルファラン・プレドニゾン→レナリドミド維持療法（MPR-R）
A Phase 3 Study Evaluating the Efficacy and Safety of Lenalidomide (Len) Combined with Melphalan and Prednisone Followed by Continuous Lenalidomide Maintenance (MPR-R) in Patients (Pts) ≧ 65 Years (Yrs) with Newly Diagnosed Multiple Myeloma (NDMM): Updated Results for Pts Aged 65-75 Yrs Enrolled in MM-015
http://ash.confex.com/ash/2011/webprogram/Paper37604.html

476：導入療法；メルファラン＋プレドニゾン±ボルテゾミブ（MP±V）
Continued Overall Survival Benefit After 5 Years’ Follow-up with Bortezomib-Melphalan-Prednisone (VMP) Versus Melphalan-Prednisone (MP) in Patients with Previously Untreated Multiple Myeloma, and No Increased Risk of Second Primary Malignancies: Final Results of the Phase 3 VISTA Trial
http://ash.confex.com/ash/2011/webprogram/Paper37551.html

477：維持療法；ボルテゾミブ＋サリドマイド（VT）対ボルテゾミブ＋プレドニゾン（VP）
Maintenance Therapy with Bortezomib Plus Thalidomide (VT) or Bortezomib Plus Prednisone (VP) In Elderly Myeloma Patients Included In the GEM2005MAS65 Spanish Randomized Trial
http://ash.confex.com/ash/2011/webprogram/Paper39307.html

478：導入療法；ボルテゾミブ併用療法
Efficacy and Safety of Three Bortezomib-Based Combinations in Elderly, Newly Diagnosed Multiple Myeloma Patients: Results From All Randomized Patients in the Community-Based, Phase 3b UPFRONT Study
http://ash.confex.com/ash/2011/webprogram/Paper37808.html

479：導入療法；MLN9708（経口プロテアソーム阻害剤）＋レナリドミド＋デキサメタゾン
Phase 1/2 Study of Oral MLN9708, A Novel, Investigational Proteasome Inhibitor, in Combination with Lenalidomide and Dexamethasone in Patients with Previously Untreated Multiple Myeloma (MM)
http://ash.confex.com/ash/2011/webprogram/Paper39737.html

480：救援療法；ボリノスタット（ヒストン脱アセチル化酵素阻害剤）＋ボルテゾミブ
Vantage 095: Vorinostat in Combination with Bortezomib in Salvage Multiple Myeloma Patients: Final Study Results of a Global Phase 2b Trial
http://ash.confex.com/ash/2011/webprogram/Paper37976.html

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◆形質細胞疾患の前向き試験
http://ash.confex.com/ash/2011/webprogram/Session3600.html
--------------------------------------------
991：くすぶり型MM；レナリドミド＋デキサメタゾン導入＋維持
Smoldering Multiple Myeloma (SMM) At High-Risk of Progression to Symptomatic Disease: A Phase III, Randomized, Multicenter Trial Based On Lenalidomide-Dexamethasone (Len-Dex) As Induction Therapy Followed by Maintenance Therapy with Len Alone Vs No Treatment
http://ash.confex.com/ash/2011/webprogram/Paper40382.html

992：ALアミロイドーシス
ALchemy - A Large Prospective ‘Real World’ Study of Chemotherapy in AL Amyloidosis
http://ash.confex.com/ash/2011/webprogram/Paper44556.html

993：MRC骨髄腫IX試験（サリドマイド、6年追跡）
MRC Myeloma IX, 6 Year Median Follow-up (FU) Highlights the Importance of Long-Term FU in Myeloma Clinical Trials and Differential Effects of Thalidomide in High- and Low-Risk Disease
http://ash.confex.com/ash/2011/webprogram/Paper42678.html

994：染色体異常（フランスIFM）
Incidence and Prognostic Value of Chromosomal Abnormalities in Elderly Patients with myeloma : The IFM Experience on 1095 Patients
http://ash.confex.com/ash/2011/webprogram/Paper38835.html

995：ALアミロイドーシス（欧州共同研究）
European Collaborative Study of Treatment Outcomes in 347 Patients with Systemic AL Amyloidosis with Mayo Stage III Disease
http://ash.confex.com/ash/2011/webprogram/Paper41010.html

996：レナリドミドによる二次がん
Second Primary Malignancies in Newly Diagnosed Multiple Myeloma Patients Treated with Lenalidomide: Analysis of Pooled Data in 2459 Patients
http://ash.confex.com/ash/2011/webprogram/Paper37311.html

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◆移植関連
--------------------------------------------
823：トータルセラピー3における二次がん
Second Malignancies in Total Therapy 3 Trials for Newly Diagnosed Multiple Myeloma: Influence of Lenalidomide Versus Thalidomide in Maintenance Phases
http://ash.confex.com/ash/2011/webprogram/Paper43567.html

824：2回目の移植（自家移植と同種移植の比較）
Second Transplants in Relapsed Multiple Myeloma (MM): Autologous (AHCT) Versus Non-Myeloablative/Reduced Intensity (NST/RIC) Allogeneic Transplantation (AlloHCT)
http://ash.confex.com/ash/2011/webprogram/Paper44163.html

825：自家移植後の再発パターン
Patterns of Disease Relapse and Progression in Patients with Multiple Myeloma After First Line Therapy with Autologous Stem Cell Transplantation: Implications for Patient Monitoring After Transplantation
http://ash.confex.com/ash/2011/webprogram/Paper38460.html

826：CR定義の比較
Conventionally-Defined and PET/CT-Defined Complete Response (CR) to Novel Agent-Based Induction Therapy and Autologous Stem-Cell Transplantation (ASCT) In Multiple Myeloma (MM): A Prospective Study of Clinical and Prognostic Implications
http://ash.confex.com/ash/2011/webprogram/Paper37215.html

827：自家移植後の微小残存病変
LONG-TERM RESULTS of the GIMEMA VTD Consolidation TRIAL In Autografted MULTIPLE Myeloma PATIENTS (VEL-03-096): IMPACT of Minimal RESIDUAL DISEASE Detection by REAL Time Quantitative PCR On LATE Recurrences and Overall SURVIVAL.
http://ash.confex.com/ash/2011/webprogram/Paper36584.html

828：同種移植後再発に対するボルテゾミブ＋デキサメタゾン→DLI
High Response Rates to Bortezomib-Dexamethasone Followed by Donor Lymphocyte Infusions in Patients with Multiple Myeloma Relapsing After Allogeneic Stem Cell Transplantation: Results of a Multicentric Prospective Phase II Study
http://ash.confex.com/ash/2011/webprogram/Paper41511.html

332：自家移植の結果予測のための染色体異常とISS
Combining Information Regarding Chromosomal Aberrations t(4;14), Del(17p13) and the Copy Number of 1q21 with the International Staging System Classification Allows Stratification of Myeloma Patients Undergoing Autologous Stem Cell Transplantation: Results From the HOVON-65/GMMG HD4 Trial
http://ash.confex.com/ash/2011/webprogram/Paper37891.html

333：非高リスク染色体異常の自家移植への影響
Impact of Non High-Risk Chromosomal Abnormalities on the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma
http://ash.confex.com/ash/2011/webprogram/Paper44033.html

504：再発後の2回目の自家移植
Second Autologous Transplants for Multiple Myeloma (MM) Relapse After a Prior Autologous Transplant (AHCT) ? a Report From the Center for International Blood and Marrow Transplant Research (CIBMTR)
http://ash.confex.com/ash/2011/webprogram/Paper43673.html
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米国血液学会（ASH）の2011年会議がサンディエゴで12月10〜13日に開催されますが、そのアブストラクトが公開されました。患者にとって興味が高そうな治療関係のみとりあえず集めてみました（生物学、病態生理学、前臨床試験については割愛）。

●検察メイン
http://ash.confex.com/ash/2011/webprogram/start.html

●653.骨髄腫：治療（移植以外）
◆再発/難治性骨髄腫患者の新薬
http://ash.confex.com/ash/2011/webprogram/Session3599.html
◆骨髄腫の新薬
http://ash.confex.com/ash/2011/webprogram/Session3522.html
◆骨髄腫の併用療法
http://ash.confex.com/ash/2011/webprogram/Session3523.html
◆試験I
http://ash.confex.com/ash/2011/webprogram/Session3598.html
◆形質細胞疾患の前向き試験
http://ash.confex.com/ash/2011/webprogram/Session3600.html
◆ポスターI
http://ash.confex.com/ash/2011/webprogram/Session3525.html
◆ポスターII
http://ash.confex.com/ash/2011/webprogram/Session3730.html
◆ポスターIII（Poster III）
http://ash.confex.com/ash/2011/webprogram/Session3731.html

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◆再発/難治性骨髄腫患者の新薬
http://ash.confex.com/ash/2011/webprogram/Session3599.html
--------------------------------------------
811：ボリノスタット（ヒストン脱アセチル化酵素阻害剤）とボルテゾミブの併用療法
Vantage 088: Vorinostat in Combination with Bortezomib in Patients with Relapsed/Refractory Multiple Myeloma: Results of a Global, Randomized Phase 3 Trial
http://ash.confex.com/ash/2011/webprogram/Paper37972.html

812：ポマリドマイド（サリドマイド誘導体）とデキサメタゾンの併用療法
High Response Rates to Pomalidomide and Dexamethasone in Patients with Refractory Myeloma, Final Analysis of IFM 2009-02
http://ash.confex.com/ash/2011/webprogram/Paper37679.html


813：カーフィルゾミブ（プロテアソーム阻害剤）単剤療法
Final Results From the Bortezomib-naive Group of PX-171-004, a Phase 2 Study of Single-Agent Carfilzomib in Patients with Relapsed and/or Refractory MM
http://ash.confex.com/ash/2011/webprogram/Paper37208.html


814：パノビノスタット（汎脱アセチル化酵素阻害剤）とボルテゾミブ・デキサメタゾンとの併用療法
Phase II Study of the Pan-Deacetylase Inhibitor Panobinostat in Combination with Bortezomib and Dexamethasone in Relapsed and Bortezomib-Refractory Multiple Myeloma (PANORAMA 2)
http://ash.confex.com/ash/2011/webprogram/Paper41145.html

815：ペリホシン(Akt阻害剤）ととボルテゾミブ・デキサメタゾンとの併用療法
Perifosine Plus Bortezomib and Dexamethasone in Relapsed / Refractory Multiple Myeloma Patients Previously Treated with Bortezomib: Final Results of a Phase I/II Trial
http://ash.confex.com/ash/2011/webprogram/Paper43511.html


816：MLN9708（経口プロテアソーム阻害剤）
Weekly Dosing of the Investigational Oral Proteasome Inhibitor MLN9708 in Patients with Relapsed and/or Refractory Multiple Myeloma: Results From a Phase 1 Dose-Escalation Study
http://ash.confex.com/ash/2011/webprogram/Paper42684.html

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◆骨髄腫の新薬
http://ash.confex.com/ash/2011/webprogram/Session3522.html
--------------------------------------------
301：MLN9708（経口プロテアソーム阻害剤）
Investigational Agent MLN9708, An Oral Proteasome Inhibitor, in Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (MM): Results From the Expansion Cohorts of a Phase 1 Dose-Escalation Study
http://ash.confex.com/ash/2011/webprogram/Paper37860.html

302：マリゾニブ（NPI-0052、経口プロテアソーム阻害剤）
Phase 1 Clinical Evaluation of Twice-Weekly Marizomib (NPI-0052), a Novel Proteasome Inhibitor, in Patients with Relapsed/Refractory Multiple Myeloma (MM)
http://ash.confex.com/ash/2011/webprogram/Paper37217.html

303：エロツズマブ（CS1抗体）のレナリドミド・低量デキサメタゾンとの併用療法
A Phase 2 Study of Elotuzumab in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma
http://ash.confex.com/ash/2011/webprogram/Paper36976.html

304：ベンダムスチン（アルキル化剤）のレナリドミド・デキサメタゾンとの併用療法
Combination of Bendamustine, Lenalidomide, and Dexamethasone (BLD) in Patients with Refractory or Relapsed Multiple Myeloma Is Safe and Highly Effective: Results of Phase I/II Open-Label, Dose Escalation Study
http://ash.confex.com/ash/2011/webprogram/Paper41680.html

305：BT062（CD138抗体）
BT062, An Antibody-Drug Conjugate Directed Against CD138, Shows Clinical Activity in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma
http://ash.confex.com/ash/2011/webprogram/Paper42689.html

306：AZD6244（MEK1/2阻害剤）
Molecular Characterization and Clinical Correlations of MEK1/2 Inhibition (AZD6244) in Relapse or Refractory Multiple Myeloma: Analysis From a Phase II Study
http://ash.confex.com/ash/2011/webprogram/Paper42295.html

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◆骨髄腫の併用療法
http://ash.confex.com/ash/2011/webprogram/Session3523.html
--------------------------------------------
631：カーフィルゾミブ＋レナリドミド＋低量デキサメタゾン（CRd）
Final Results of a Frontline Phase 1/2 Study of Carfilzomib, Lenalidomide, and Low-Dose Dexamethasone (CRd) in Multiple Myeloma (MM)
http://ash.confex.com/ash/2011/webprogram/Paper39029.html

632：ポマリドマイド＋シクロホスファミド＋プレドニゾン（PCP）
A Phase I/II Study of Pomalidomide-Cyclophosphamide-Prednisone (PCP) in Patients with Multiple Myeloma Relapsed/Refractory to Lenalidomide
http://ash.confex.com/ash/2011/webprogram/Paper37516.html

633：カーフィルゾミブ＋サリドマイド＋デキサメタゾン（CARTHADEX）
Carfilzomib Combined with Thalidomide and Dexamethasone (CARTHADEX) As Induction Treatment Prior to High-Dose Melphalan (HDM) in Newly Diagnosed Patients with Multiple Myeloma (MM). A Trial of the European Myeloma Network EMN
http://ash.confex.com/ash/2011/webprogram/Paper37824.html

634：ポマリドマイド±低量デキサメタゾン
Randomized, Open Label Phase 1/2 Study of Pomalidomide (POM) Alone or in Combination with Low-Dose Dexamethasone (LoDex) in Patients (Pts) with Relapsed and Refractory Multiple Myeloma Who Have Received Prior Treatment That Includes Lenalidomide (LEN) and Bortezomib (BORT): Phase 2 Results
http://ash.confex.com/ash/2011/webprogram/Paper38850.html

635：クラリスロマイシン＋ポマリドマイド＋デキサメタゾン（ClaPD）
ClaPD (Clarithromycin/[BiaxinR], Pomalidomide, Dexamethasone) Therapy in Relapsed or Refractory Multiple Myeloma
http://ash.confex.com/ash/2011/webprogram/Paper40918.html

636：移植±イディオタイプ・パルス樹状細胞ワクチン
Matched Case Control Analysis Comparing Long Term Survival of Multiple Myeloma Patients Who Received Stem Cell Transplant with and without Idiotype-Pulsed Dendritic Cell Vaccine
http://ash.confex.com/ash/2011/webprogram/Paper43255.html

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つづく