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David Siegel, MD John Theurer Cancer Center Hackensack, New Jersey, USA A phase 1 (Ph1) trial of MK-3475 combined with lenalidomide (Len) and low-dose dexamethasone (Dex) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) RRMM patients refractory to proteasome inhibitors and immunomodulatory drugs (IMiD) have a very poor outcome. PD-L1 expressed on most MM plasma cells is a potential mechanism of immune evasion. MK-3475 is a potent, highly selective, humanized IgG4/kappa isotype, anti-PD-1 monoclonal antibody designed to block PD-1 interaction with PD-L1 and PD-L2, enhancing lymphocytic activity, tumor regression and immune rejection. Visit our website at: http://www.myeloma.org

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David Siegel, MD John Theurer Cancer Center Hackensack, New Jersey, USA A phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone (QUAD) in relapsed and/or refractory multiple myeloma (MM) Carfilzomib in combination with an immunomodulatory agent has proven efficacy in NDMM and RRMM. There is also synergistic activity of the combination of a proteasome inhibitor and a histone-deacetylase inhibitor Methods: To determine the toxicity and activity of the quadruplet using carfilzomib with lenalidomide, vorinostat and dexamethasone. The primary objectives were to determine the maximum tolerated dose (MTD) and the safety/tolerability of QUAD. Secondary objectives included ORR, DOR, TTP and TTNT.…

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David Siegel, MD John Theurer Cancer Center Hackesack, New Jersey, USA Phase 1-2 open-label, multiple-dose, dose-escalation study to evaluate the safety and tolerability of intravenous infusion of SNS01-T, a first-in-class modulator of eukaryotic translation initiation factor 5A (eIF5A) in patients (pts) with relapsed or refractory B-cell malignancies eIF5A has been implicated in the regulation of cell proliferation, apoptosis, and inflammation. It is the only known protein to be modified by hypusination, and is highly conserved across species and is active in plants and animals. Hypusinated eIF5A, the predominant form in normal and cancer cells, is involved in cell survival and…

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Torben Plesner, MD Department of Hematology, Vejle Hospital Vejle, Denmark Daratumumab (DARA) (HuMax-CD38), a human IgG1? monoclonal antibody effectively mediates destruction of CD38-expressing malignant plasma cells. In the first-in-human dose-escalation study, 42% of heavily pretreated patients with relapsed or relapsed, refractory (RR) multiple myeloma (MM) treated with DARA alone (?4mg/kg) achieved partial response (PR) and 25% had minimal response (MR) (modified IMWG guidelines). In preclinical studies, DARA + lenalidomide (LEN) enhanced killing of MM cells in vitro.We evaluated safety, pharmacokinetics (PK) and efficacy of DARA + LEN + dexamethasone (DEX) in patients with relapsed or RR MM. Visit our website…

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Matthias Weiss, MD Marshfield Clinic Marshfield, Wisconsin, USA ECOG multiple myeloma (MM) clinical trial (CT) accrual performance evaluation utilizing the NCI–Trial Complexity and Elements Scoring (NCI-TCES) and the NCI Myeloma Steering Committee Accrual Working Group (NCI MYSC AWG) scoring models. Accrual to NCI CTs is often slower than planned and at times mandating premature closure resulting in loss of valuable resources and delay of scientific progress. The NCI MYSC AWG identified 10 barriers to accrual (BtA) to MM CTs (reimbursement, competing treatment options, treatment at NCI designated sites only, etc.). The NCI-TCES was created to objectively assess CT complexity (study…

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Jeremy Larsen, MD Mayo Clinic Rochester, Minnesota, USA Free light chain assay and cytogenetic abnormalities for identification of high-risk smoldering myeloma Translocation (4;14) and deletion 17p in smoldering multiple myeloma (SMM) have been identified as high risk cytogenetic abnormalities (CAs). Risk stratification incorporating CAs and biomarkers are needed to identify high risk SMM patients. The aim of this study was to determine the predictive value of the free light chain (FLC) assay in combination with high-risk CAs. Visit our website at: http://www.myeloma.org

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Paul Richardson, MD Dana-Farber Cancer Institute Boston, Massachusetts, USA Panorama 1: A randomized, double-blind, phase 3 study of panobinostat or placebo plus bortezomib and dexamethasone in relapsed or relapsed and refractory multiple myeloma Panobinostat (PAN) is a potent pan-deacetylase inhibitor that demonstrates synergistic antimyeloma activity when combined with bortezomib (BTZ) + dexamethasone (Dex). Early studies demonstrated durable responses in patients (pts) with relapsed (Rel) and relapsed/refractory (RR) multiple myeloma (MM) treated with PAN + BTZ + Dex. This initiated the PANORAMA 1 study, presented herein. Visit our website at: http://www.myeloma.org

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Paul Richardson, MD Dana-Farber Cancer Institute Boston, Massachusetts, USA MM-005: Phase 1 trial of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) in lenalidomide (LEN)-refractory and proteasome inhibitor (PI)-exposed myeloma. Combination treatment (Tx) with IMiDs immunomodulatory agents and PIs demonstrated substantial efficacy in myeloma patients (pts) (Richardson, Blood, 2010). MM-005 was designed to identify the optimal PVD dose for a phase 3 trial (MM-007) comparing PVD vs. BORT + LoDEX in RRMM pts. A secondary objective examined subcutaneous (SC) BORT as part of PVD Tx. Visit our website at: http://www.myeloma.org

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Paul Richardson, MD Dana-Farber Cancer Institute Boston, Massachusetts, USA Preliminary safety and efficacy of TH-302, an investigational hypoxia-targeted drug, and dexamethasone (dex) in patients (pts) with relapsed/refractory multiple myeloma (RR MM) While alkylators, IMiDs and proteasome inhibitors are current standard treatment for pts with MM, the presence of hypoxia in the diseased bone marrow (Colla, Leukemia 2010) presents a new therapeutic target for MM. TH-302 is a novel 2-nitroimidazole prodrug of the DNA alkylator bromo-isophosphoramide mustard that is selectively activated under hypoxia. Synergistic induction of apoptosis in MM cells by TH-302 and bortezomib was shown in MM models in vivo…

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Paul Richardson, MD Dana-Farber Cancer Institute Boston, Massachusetts, USA DETERMINATION trial: A phase III multi-center study examining the timing of stem cell transplant for MM The DETERMINATION study will have 1300 patients (700 in France and over 600 in the US) to determine when transplant is best used in newly diagnosed myeloma patients now that newer therapies are available. The study will also look at how the Revlimid/Velcade/Dex combo works as initial treatment and how lenalidomide affects progression as maintenance therapy. Visit our website at: http://www.myeloma.org

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Charlotte Pawlyn, MD Institute of Cancer Research Sutton, United Kingdom Treatment with immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) has dramatically increased response rates and survival for myeloma patients over the last decade. Triplet drug combinations are more effective than doublets or single agents. The more recently developed IMiD lenalidomide, with a different spectrum of effects to thalidomide, is an excellent option for induction therapy due to its oral administration and lack of significant peripheral neuropathy (PN) when compared with bortezomib and thalidomide. Visit our website at: http://www.myeloma.org

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Xin Shelley Wang, MD MD Anderson Cancer Center Houston, Texas, USA Prevalence of high symptom burden and its impact on functioning and quality of life in patients with multiple myeloma 3-9 months following autologous transplant Although multiple myeloma (MM) patients are expected to have lower disease burden post autologous hematopoietic stem cell transplantation (AuSCT), symptom burden and its impact on patient’s quality of life (QoL) have not been prospectively studied in this time period, when maintenance therapy may be implemented. Visit our website at: http://www.myeloma.org

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Mohammed Jaloudi, MD, of Tawam Hospital, Al Ain, United Arab Emirates, discusses the value of genomic profiling for individualising and improving adjuvant therapy for breast cancer patients. More recently, multigene assays, such as the Oncotype DX® Breast Cancer Assay, are being considered in addition to classic clinicopathological tools to guide treatment decisions for breast cancer patients. This content is supported by Genomic Health, Inc. European Medical Journal Website: http://emjreviews.com/ Twitter: https://twitter.com/EMJReviews Facebook: https://www.facebook.com/emjreviews

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Saad Z. Usmani, MD Levine Cancer Institute – Morehead Charlotte, North Carolina, USA Continuous lenalidomide (LEN) therapy versus observation following nonimmunomodulatory compound-based induction therapy in newly diagnosed multiple myeloma (NDMM): MM-027 trial Several recent trials have shown improvements in progression-free survival (PFS) with continuous LEN treatment (Tx) in NDMM patients (pts). PFS was 45%-59% higher using LEN therapy vs. control arm and rates of overall survival (OS) were consistently improved (Attal, NEJM 2012; Facon, ASH 2013, McCarthy, NEJM 2012; Palumbo, NEJM 2012, Palumbo ASCO 2013). Therefore an effective strategy of continuous Tx is of great importance to outcomes. Visit our…

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Thomas G. Martin, MD University of California SF San Francisco, California, USA A phase Ib dose escalation trial of SAR650984 (Anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma SAR650984 (SAR) is a humanized IgG1 monoclonal antibody that binds selectively to a unique epitope on human CD38 receptor. SAR kills tumor cells via antibody-dependent cellular-mediated cytotoxicity, complement-dependent cytotoxicity, direct apoptosis induction without secondary crosslinking and allosteric inhibition on CD38 enzymatic activity. Visit our website at: http://www.myeloma.org

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James R. Berenson, MD Institute for Myeloma & Bone Cancer Research West Hollywood, California, USA Results of the dose-escalation portion of a phase 1/2 study (CHAMPION-1) investigating weekly carfilzomib in combination with dexamethasone for patients with relapsed or refractory multiple myeloma Carfilzomib (CFZ) is a selective proteasome inhibitor approved in the US for the treatment of relapsed and refractory multiple myeloma (MM). This multicenter, single-arm phase 1/2 study (NCT01677858) is evaluating the safety and efficacy of once-weekly CFZ with dexamethasone (DEX). Visit our website at: http://www.myeloma.org

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Thomas G. Martin, MD University of California SF San Francisco, California, USA A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma SAR650984 (SAR) is a naked humanized IgG1 monoclonal antibody that binds to the CD38 receptor. SAR kills tumor cells via ADCC, CDC, direct apoptosis without secondary crosslinking and allosteric inhibition on CD38 enzymatic activity. Data on relapsed /refractory multiple myeloma (RRMM) patients (pts) in the dose escalation phase of the study are reported. (NCT01084252). Visit our website at: http://www.myeloma.org

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Antonio Palumbo, MD University of Torino Torino Italy Continuous treatment (CT) versus fixed duration of therapy (FDT) in newly diagnosed myeloma patients: PFS1, PFS2, OS endpoints Continuous therapy significantly prolongs remission duration, resistant relapse may reduce the duration of subsequent remission which can negatively impact on OS. PFS1 defines the time from start of therapy to the occurrence of 1st relapse. PFS2 is defined as per EMA as the time from start of therapy to the occurrence of 2nd relapse, incorporating the duration of both 1st and 2nd remission. We evaluated PFS1, PFS2 and OS in newly diagnosed multiple myeloma…

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Keith K. Stewart, MB ChB Mayo Clinic Scottsdale, Arizona, USA E1A06: A phase III trial comparing melphalan, prednisone, and thalidomide (MPT) versus melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed multiple myeloma (MM) Melphalan, prednisone and thalidomide (MPT) is an accepted regimen in newly diagnosed MM. Early studies suggested that lenalidomide (R) might be substituted for thalidomide (T) with equal efficacy and less toxicity. We present E1A06, a randomized, multicenter phase 3 trial comparing MPT vs. MPR in pts with untreated, symptomatic, transplant ineligible MM. Visit our website at: http://www.myeloma.org

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Mark A. Fiala, BS, CCRN Washington University School of Medicine Division of Oncology, Department of Medicine Saint Louis, MO, USA The Impact of Race and Socio-Economic Status on Survival in Multiple Myeloma Advances in multiple myeloma (MM) therapies have improved overall survival (OS), however, not all population subgroups have benefited equally from these advances. Population-based studies suggest that black patients (pts) with MM have a much higher mortality rate than white pts, however, in several studies, after controlling for treatment, OS was similar or superior for black pts. This discrepancy suggests that the poorer outcomes observed in black pts are…

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Hope S. Rugo, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, explains that the use of genomic tests for breast cancer patients in clinical practice is affected by numerous factors, including the ability of the test to predict response to treatment and the ability of the test to provide meaningful prognostic information in addition to the information provided by classic clinicopathologic tools. This content is supported by Genomic Health, Inc. European Medical Journal Website: http://emjreviews.com/ Twitter: https://twitter.com/EMJReviews Facebook: https://www.facebook.com/emjreviews

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Joseph Gligorov, MD, PhD, of Sorbonne Université, Paris, France, discusses the use of genomic tests as predictive tools for adjuvant chemotherapy benefit in the management of patients with breast cancer. This content is supported by Genomic Health, Inc. European Medical Journal Website: http://emjreviews.com/ Twitter: https://twitter.com/EMJReviews Facebook: https://www.facebook.com/emjreviews

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Institute, Boston, MA, explains the development of multigene tests, such as the Oncotype DX® Breast Cancer Assay and the PAM50 test, for classifying breast cancer into different subtypes. Luminal A and B subtypes of breast cancer may have important predictive value in the clinic. This content is supported by Genomic Health, Inc. European Medical Journal Website: http://emjreviews.com/ Twitter: https://twitter.com/EMJReviews Facebook: https://www.facebook.com/emjreviews

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Paolo A. Ascierto, MD, of Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy, discusses CheckMate 067, a randomised, double-blind, phase 3 trial of nivolumab monotherapy or nivolumab combined with ipilimumab versus ipilimumab monotherapy in patients with previously untreated unresectable or metastatic melanoma.

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Since 2003, the IMF has honored an outstanding physician each year with the Robert A. Kyle Lifetime Achievement Award. The award, named for its first recipient, is presented to an individual whose body of work in the field of myeloma has made significant advances in research, treatment and care of myeloma patients. Our honorees work reflects the words of Dr. William Mayo, founder of Mayo Clinic, who challenged the nature of patient care nearly a century ago when he said The needs of the patient are the only needs to be considered. Visit our website at: http://www.myeloma.org Find us online:…

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Neal Shore, MD, FACS, of Atlantic Urology Clinics, Myrtle Beach, SC, discusses the interim analysis of PROCEDE?1000, a prospective registry evaluating the impact of Prolaris®, a cell cycle progression (CCP) test, on personalising treatment decisions following biopsy in newly diagnosed patients with prostate cancer. European Medical Journal Website: http://emjreviews.com/ Twitter: https://twitter.com/EMJReviews Facebook: https://www.facebook.com/emjreviews

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Sumanta K. Pal, MD, of City of Hope Comprehensive Cancer Center, Duarte, CA, discusses the results of a randomised, phase 2, three-arm trial of lenvatinib, everolimus, and lenvatinib combined with everolimus in patients with metastatic renal cell carcinoma.

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, Villejuif, France, reviews the clinical development of new chemotherapy-based approaches for the management of patients with advanced prostate cancer. European Medical Journal Website: http://emjreviews.com/ Twitter: https://twitter.com/EMJReviews Facebook: https://www.facebook.com/emjreviews

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Keith Kerr, BSc, MB, ChB, FRCPath, FRCPE, of the University of Aberdeen, Aberdeen, Scotland, reviews the development of immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1) signalling pathway and the identification of predictive biomarkers of response to immunotherapies for the management of patients with lung cancer. European Medical Journal Website: http://emjreviews.com/ Twitter: https://twitter.com/EMJReviews Facebook: https://www.facebook.com/emjreviews

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At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Caroline Robert, MD, PhD, of Institut Gustave Roussy, Villejuif, France, considers the impact of available and emerging targeted therapies and immunotherapies on the current treatment landscape in melanoma. European Medical Journal Website: http://emjreviews.com/ Twitter: https://twitter.com/EMJReviews Facebook: https://www.facebook.com/emjreviews

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IMWG Myeloma Experts debate the latest trends in treatment June 10, 2015 Vienna Austria Drs. Brian Durie, Joseph Mikhael, Ola Landgren, and Paul Richardson discusses the following topics: Diagnostic Criteria Revised ISS staging and personalized medicine MRD testing/response criteria The challenge of double refractory disease Drug costs and access: 2015 and beyond Visit our website at: http://www.myeloma.org Find us online: Facebook: http://facebook.com/myeloma Google+: http://gplus.to/imfmyeloma IMF on twitter: @IMFMyeloma (http://twitter.com/imfmyeloma) Dr. Durie on twitter: @BrianDurieMD (http://twitter.com/brianduriemd)

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IMWG Myeloma Experts debate the latest trends in treatment June 10, 2015 Vienna Austria Drs. Brian Durie, Joseph Mikhael, Ola Landgren, and Paul Richardson discusses the following topics: Diagnostic Criteria Revised ISS staging and personalized medicine MRD testing/response criteria The challenge of double refractory disease Drug costs and access: 2015 and beyond Visit our website at: http://www.myeloma.org Find us online: Facebook: http://facebook.com/myeloma Google+: http://gplus.to/imfmyeloma IMF on twitter: @IMFMyeloma (http://twitter.com/imfmyeloma) Dr. Durie on twitter: @BrianDurieMD (http://twitter.com/brianduriemd)

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