Multiple Myeloma
April 2018 Issue

Nearly every major medical breakthrough over the past 50 years can be attributed to new discoveries that were made possible through meticulous biomedical research. Many diseases and conditions that previously took a heavy toll on patients in terms of both morbidity and mortality are now either treatable or preventable thanks in large part to painstaking research that expanded the frontiers of scientific knowledge and moved the most promising basic research developments into tangible health benefits through human clinical trails. Ongoing research is also the key that will open the door to additional major medical advances and breakthroughs in the future.

Our staff at Medifocus is committed to keeping our subscribers to the Medifocus Digest Alert on Multiple Myeloma abreast of the latest new research developments that have recently been published in the medical literature for this condition. In this issue of the Digest Alert, you will find a focused list of hand-picked journal article references that represent the latest advances in basic and clinical research for Multiple Myeloma. These articles represent the current state-of-the-art of the research that will hopefully lead to additional major advances and breakthroughs in the clinical management of Multiple Myeloma. You can access the summaries of each article referenced below by simply clicking on the article Title.

We will continue to update you with the latest scientific and clinical developments through the Medifocus Digest Alert on Multiple Myeloma every 3 months. Thank you for your ongoing subscription to this publication.

Elliot Jacob, Ph.D.
Vice-President - Content, Inc.

1:The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma.
Authors:Breitkreutz I, Podar K, Figueroa-Vazquez V, Wilhelm S, Hayden PJ, Anderson KC, Raab MS
Institution:Max-Eder-Group 'Experimental Therapies for Hematologic Malignancies', Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany.; LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.; Department of Medicine V, Heidelberg University Hospital, INF 410, 69120, Heidelberg, Germany.; Department of Internal Medicine, University Hospital Krems, Karl Landsteiner University of Health Sciences, 3500, Krems, Austria.; Bayer HealthCare Pharmaceuticals, Montville, 07045, NJ, USA.
Journal:Ann Hematol. 2018 May;97(5):839-849. doi: 10.1007/s00277-018-3237-5. Epub 2018 Jan 23.

2:Risk of adverse events associated with front-line anti-myeloma treatment in Medicare patients with multiple myeloma.
Authors:Chen Y, Lairson DR, Chan W, Du XL
Institution:Department of Epidemiology, Human Genetics, and Environmental Science, School of Public Health, University of Texas Health Science Center in Houston, 1200 Pressler Street, RAS-E631, Houston, TX, 77030, USA. University of Texas Health Science Center in Houston, Houston, TX, USA. Science Center in Houston, Houston, TX, USA. Public Health, University of Texas Health Science Center in Houston, 1200 Pressler Street, RAS-E631, Houston, TX, 77030, USA.
Journal:Ann Hematol. 2018 May;97(5):851-863. doi: 10.1007/s00277-018-3238-4. Epub 2018 Jan 15.

3:Salvage therapy post pomalidomide-based regimen in relapsed/refractory myeloma.
Authors:Fouquet G, Karlin L, Macro M, Caillot D, Roussel M, Arnulf B, Pegourie B, Petillon MO, Mathiot C, Hulin C, Kolb B, Stoppa AM, Brechiniac S, Rodon P, Dib M, Tiab M, Richez V, Araujo C, Wetterwald M, Garderet L, Royer B, Perrot A, Benboubker L, Decaux O, Escoffre-Barbe M, Fermand JP, Moreau P, Avet-Loiseau H, Attal M, Facon T, Leleu X
Institution:Maladies du sang, CHRU de Lille, Lille, France. France.
Journal:Ann Hematol. 2018 May;97(5):831-837. doi: 10.1007/s00277-018-3236-6. Epub 2018 Jan 12.

4:A question of class: Treatment options for patients with relapsed and/or refractory multiple myeloma.
Authors:Cook G, Zweegman S, Mateos MV, Suzan F, Moreau P
Institution:St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK. Electronic address:
Journal:Crit Rev Oncol Hematol. 2018 Jan;121:74-89. doi: 10.1016/j.critrevonc.2017.11.016. Epub 2017 Dec 5.

5:Bisphosphonates in multiple myeloma: an updated network meta-analysis.
Authors:Mhaskar R, Kumar A, Miladinovic B, Djulbegovic B
Institution:Center for Evidence Based Medicine and Health Outcomes Research, University of South Florida, Tampa, Florida, USA.
Journal:Cochrane Database Syst Rev. 2017 Dec 18;12:CD003188. doi: 10.1002/14651858.CD003188.pub4.

6:The therapeutic effect of modified Huangqi Guizhi Wuwu Tang for multiple myeloma: An 18-year follow-up case report.
Authors:Tian M, Huang H
Institution:aBasic Medicine CollegebInternational Jingfang Institute, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
Journal:Medicine (Baltimore). 2017 Dec;96(49):e9074. doi: 10.1097/MD.0000000000009074.

7:Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma.
Authors:Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J
Institution:From University Hospital of Salamanca-Instituto de Investigacion Biomedica de Salamanca, Salamanca (M.-V.M.), and Clinica Universidad de Navarra-Centro de Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, Centro de Investigacion Biomedica en Red de Cancer, Pamplona (J.S.-M.) - both in Spain; National and Kapodistrian University of Athens, Athens (M.A.D.); the Institute of Hematology, Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna (M. Cavo), and Azienda Ospedaliera 'Santa Maria,' Terni (A.M.L.) - both in Italy; Japanese Red Cross Medical Center, Department of Hematology, Tokyo (K.S.); University of Chicago Medical Center, Chicago (A.J.); Wurzburg University Medical Center, Wurzburg, Germany (S.K.); Universite Catholique de Louvain (UCL), Centre Hospitalier Universitaire UCL Namur, Yvoir (C.D.), and Janssen Research and Development, Beerse (W.D.) - both in Belgium; Champalimaud Center for the Unknown, Lisbon, Portugal (P.L.); Semmelweis Egyetem, Budapest, Hungary (Z.N.); Dnepropetrovsk City Clinical Hospital #4, Dnepropetrovsk, Ukraine (P.K.); University Hospital Brno, Brno, Czech Republic (L.P.); University Hospitals Birmingham NHS Foundation Trust, Birmingham (M. Cook), and Leicester Royal Infirmary-Haematology, Leicester (M.G.) - both in the United Kingdom; the Department of Cancer Prevention, School of Public Health, Silesian Medical University, Katowice, Poland (S.G.); Clinica de Tratamento E, Cuiaba, Brazil (A.C.); Andrew Love Cancer Centre, Geelong, VIC, Australia (P.C.); Clinic of Professional Pathology, Saratov, Russia (T.S.); the Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea (S.-S.Y.); LTD 'Medinvent' Institute of Health, Tbilisi, Georgia (G.I.); Matsuyama Red Cross Hospital, Matsuyama, Japan (T.F.); Janssen Research and Development, Spring House, PA (C.C., R.C., W.C., M.Q.); and Janssen Research and Development, Raritan, NJ (J.W., H.N.).
Journal:N Engl J Med. 2018 Feb 8;378(6):518-528. doi: 10.1056/NEJMoa1714678. Epub 2017 Dec 12.

8:The proteasome and proteasome inhibitors in multiple myeloma.
Authors:Gandolfi S, Laubach JP, Hideshima T, Chauhan D, Anderson KC, Richardson PG
Institution:Dana-Farber Cancer Institute, 44 Binney Street, Dana 1B02, Boston, MA, 02115, USA. USA. USA. USA. USA. USA.
Journal:Cancer Metastasis Rev. 2017 Dec;36(4):561-584. doi: 10.1007/s10555-017-9707-8.

9:Lenalidomide in combination or alone as maintenance therapy following autologous stem cell transplant in patients with multiple myeloma: a review of options for and against.
Authors:Richardson PG, Holstein SA, Schlossman RL, Anderson KC, Attal M, McCarthy PL
Institution:a Dana-Farber Cancer Institute , Harvard Medical School , Boston , MA , USA. , NE , USA. Toulouse-Oncopole , Toulouse , France. NY , USA.
Journal:Expert Opin Pharmacother. 2017 Dec;18(18):1975-1985. doi: 10.1080/14656566.2017.1409207. Epub 2017 Dec 1.

10:Safety and efficacy of pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed or refractory multiple myeloma.
Authors:Cohen A, Spektor TM, Stampleman L, Bessudo A, Rosen PJ, Klein LM, Woliver T, Flam M, Eshaghian S, Nassir Y, Maluso T, Swift RA, Vescio R, Berenson JR
Institution:Oncotherapeutics, West Hollywood, CA, USA.
Journal:Br J Haematol. 2018 Jan;180(1):60-70. doi: 10.1111/bjh.14992. Epub 2017 Nov 21.

11:An overview of the role of carfilzomib in the treatment of multiple myeloma.
Authors:Ziogas DC, Terpos E, Kastritis E, Dimopoulos MA
Institution:a Department of Clinical Therapeutics , Alexandra General Hospital, National and Kapodistrian University of Athens, School of Medicine , Athens , Greece.
Journal:Expert Opin Pharmacother. 2017 Dec;18(17):1883-1897. doi: 10.1080/14656566.2017.1404575. Epub 2017 Nov 20.

12:A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107): final study results.
Authors:Spencer A, Harrison S, Zonder J, Badros A, Laubach J, Bergin K, Khot A, Zimmerman T, Chauhan D, Levin N, MacLaren A, Reich SD, Trikha M, Richardson P
Institution:Alfred Health-Monash University, Melbourne, Australia.
Journal:Br J Haematol. 2018 Jan;180(1):41-51. doi: 10.1111/bjh.14987. Epub 2017 Oct 26.

13:Novel agent-based salvage autologous stem cell transplantation for relapsed multiple myeloma.
Authors:Zannetti BA, Tacchetti P, Pantani L, Gamberi B, Tosi P, Rocchi S, Cellini C, Ronconi S, Pezzi A, Mancuso K, Rizzello I, Caratozzolo I, Martello M, Dozza L, Cavo M, Zamagni E
Institution:"Seragnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy. Bologna, Italy. Bologna, Italy. Italy. Bologna, Italy. Cura dei Tumori" Hospital, Meldola, Italy. Bologna, Italy. Bologna, Italy. Bologna, Italy. Bologna, Italy. Bologna, Italy. Bologna, Italy.
Journal:Ann Hematol. 2017 Dec;96(12):2071-2078. doi: 10.1007/s00277-017-3140-5. Epub 2017 Oct 24.

14:Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients.
Authors:Avet-Loiseau H, Bahlis NJ, Chng WJ, Masszi T, Viterbo L, Pour L, Ganly P, Palumbo A, Cavo M, Langer C, Pluta A, Nagler A, Kumar S, Ben-Yehuda D, Rajkumar SV, San-Miguel J, Berg D, Lin J, van de Velde H, Esseltine DL, di Bacco A, Moreau P, Richardson PG
Institution:Laboratory for Genomics in Myeloma, University Cancer Center of Toulouse Institut National de la Sante, Toulouse, France.; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB, Canada.; Department of Hematology-Oncology, National University Cancer Institute, Singapore.; St. Istvan, St. Laszlo Hospital, Budapest, Hungary.; 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Journal:Blood. 2017 Dec 14;130(24):2610-2618. doi: 10.1182/blood-2017-06-791228. Epub 2017 Oct 20.

15:Recurrent cardiotoxicity potentiated by the interaction of proteasome inhibitor and immunomodulatory therapy for the treatment of multiple myeloma.
Authors:Fradley MG, Groarke JD, Laubach J, Alsina M, Lenihan DJ, Cornell RF, Maglio M, Shain KH, Richardson PG, Moslehi J
Institution:Cardio-Oncology Program, Department of Cardiovascular Sciences, University of South Florida Morsani College of Medicine and H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.; Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; H. Lee Moffitt Cancer Center and Research Institute, University of South Florida Morsani College of Medicine, Tampa, FL, USA.; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Journal:Br J Haematol. 2018 Jan;180(2):271-275. doi: 10.1111/bjh.14970. Epub 2017 Oct 19.

16:Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma.
Authors:Kumar S, Kaufman JL, Gasparetto C, Mikhael J, Vij R, Pegourie B, Benboubker L, Facon T, Amiot M, Moreau P, Punnoose EA, Alzate S, Dunbar M, Xu T, Agarwal SK, Enschede SH, Leverson JD, Ross JA, Maciag PC, Verdugo M, Touzeau C
Institution:Mayo Clinic, Rochester, MN.
Journal:Blood. 2017 Nov 30;130(22):2401-2409. doi: 10.1182/blood-2017-06-788786. Epub 2017 Oct 10.

17:Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial.
Authors:Einsele H, Engelhardt M, Tapprich C, Muller J, Liebisch P, Langer C, Kropff M, Mugge LO, Jung W, Wolf HH, Metzner B, Hart C, Gramatzki M, Hertenstein B, Pfreundschuh M, Rosler W, Fischer T, Maschmeyer G, Kanz L, Hess G, Jager E, Bentz M, Durk HA, Salwender H, Hebart H, Straka C, Knop S
Institution:University Hospital Wurzburg, Wurzburg, Germany. Germany.
Journal:Br J Haematol. 2017 Nov;179(4):586-597. doi: 10.1111/bjh.14920. Epub 2017 Sep 29.

18:Bortezomib and low-dose dexamethasone with or without continuous low-dose oral cyclophosphamide for primary refractory or relapsed multiple myeloma: a randomized phase III study.
Authors:Kropff M, Vogel M, Bisping G, Schlag R, Weide R, Knauf W, Fiechtner H, Kojouharoff G, Kremers S, Berdel WE
Institution:Department of Medicine A, University Hospital Muenster, Muenster, Germany. Osnabruck, Germany. Germany.
Journal:Ann Hematol. 2017 Nov;96(11):1857-1866. doi: 10.1007/s00277-017-3065-z. Epub 2017 Sep 14.

19:Advances in immunotherapy in multiple myeloma.
Authors:Boussi L, Niesvizky R
Institution:Division of Hematology and Medical Oncology, Multiple Myeloma Center, New York City, New York, USA.
Journal:Curr Opin Oncol. 2017 Nov;29(6):460-466. doi: 10.1097/CCO.0000000000000407.

20:Adoptive cell therapy in multiple Myeloma.
Authors:Vallet S, Pecherstorfer M, Podar K
Institution:a Department of Internal Medicine , Karl Landsteiner University of Health Sciences, University Hospital , Krems an der Donau , Austria.
Journal:Expert Opin Biol Ther. 2017 Dec;17(12):1511-1522. doi: 10.1080/14712598.2017.1375095. Epub 2017 Sep 6.

21:Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM.
Authors:Moreau P, Chanan-Khan A, Roberts AW, Agarwal AB, Facon T, Kumar S, Touzeau C, Punnoose EA, Cordero J, Munasinghe W, Jia J, Salem AH, Freise KJ, Leverson JD, Enschede SH, Ross JA, Maciag PC, Verdugo M, Harrison SJ
Institution:Centre Hospitalier Universitaire de Nantes, University Hospital Hotel-Dieu, Nantes, France. University of Melbourne, Melbourne, VIC, Australia. France. Nantes, France. VIC, Australia.
Journal:Blood. 2017 Nov 30;130(22):2392-2400. doi: 10.1182/blood-2017-06-788323. Epub 2017 Aug 28.

22:Lenalidomide in combination with bendamustine and prednisolone in relapsed/refractory multiple myeloma: results of a phase 2 clinical trial (OSHO-#077).
Authors:Beck J, Schwarzer A, Glaser D, Mugge LO, Uhlig J, Heyn S, Kragl B, Mohren M, Hoffmann FA, Lange T, Schliwa T, Zehrfeld T, Becker C, Kreibich U, Winkelmann C, Edelmann T, Andrea M, Bill M, Jentzsch M, Schwind S, Niederwieser D, Ponisch W
Institution:Department of Haematology and Oncology, University of Leipzig, Johannisallee 32A, 04103, Leipzig, Germany. Germany. 04103, Leipzig, Germany. 04103, Leipzig, Germany. Germany. Germany. 04103, Leipzig, Germany. 04103, Leipzig, Germany. 04103, Leipzig, Germany. 04103, Leipzig, Germany. 04103, Leipzig, Germany.
Journal:J Cancer Res Clin Oncol. 2017 Dec;143(12):2545-2553. doi: 10.1007/s00432-017-2504-5. Epub 2017 Aug 21.

23:A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory multiple myeloma.
Authors:Shah JJ, Kaufman JL, Zonder JA, Cohen AD, Bensinger WI, Hilder BW, Rush SA, Walker DH, Tunquist BJ, Litwiler KS, Ptaszynski M, Orlowski RZ, Lonial S
Institution:Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Journal:Cancer. 2017 Dec 1;123(23):4617-4630. doi: 10.1002/cncr.30892. Epub 2017 Aug 17.

24:Systemic virotherapy for multiple myeloma.
Authors:Oliva S, Gambella M, Boccadoro M, Bringhen S
Institution:a Myeloma Unit, Division of Hematology , University of Torino, Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino , Torino , Italy.
Journal:Expert Opin Biol Ther. 2017 Nov;17(11):1375-1387. doi: 10.1080/14712598.2017.1364359. Epub 2017 Aug 10.

25:Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma.
Authors:Richardson PG, Hofmeister CC, Raje NS, Siegel DS, Lonial S, Laubach J, Efebera YA, Vesole DH, Nooka AK, Rosenblatt J, Doss D, Zaki MH, Bensmaine A, Herring J, Li Y, Watkins L, Chen MS, Anderson KC
Institution:Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.; Massachusetts General Hospital, Boston, MA, USA.; John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Journal:Leukemia. 2017 Dec;31(12):2695-2701. doi: 10.1038/leu.2017.173. Epub 2017 Jun 2.

26:Cardiovascular events during carfilzomib therapy for relapsed myeloma: practical management aspects from two case studies.
Authors:Jakubowiak AJ, DeCara JM, Mezzi K
Institution:a Department of Medicine , The University of Chicago Medicine , Chicago , IL , USA.
Journal:Hematology. 2017 Dec;22(10):585-591. doi: 10.1080/10245332.2017.1328165. Epub 2017 May 25.

27:Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma.
Authors:Dispenzieri A, Tong C, LaPlant B, Lacy MQ, Laumann K, Dingli D, Zhou Y, Federspiel MJ, Gertz MA, Hayman S, Buadi F, O'Connor M, Lowe VJ, Peng KW, Russell SJ
Institution:Department of Hematology, Mayo Clinic, Rochester, MN, USA.
Journal:Leukemia. 2017 Dec;31(12):2791-2798. doi: 10.1038/leu.2017.120. Epub 2017 Apr 25.

28:Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial.
Authors:Bahlis NJ, Corso A, Mugge LO, Shen ZX, Desjardins P, Stoppa AM, Decaux O, de Revel T, Granell M, Marit G, Nahi H, Demuynck H, Huang SY, Basu S, Guthrie TH, Ervin-Haynes A, Marek J, Chen G, Facon T
Institution:Tom Baker Cancer Center-University of Calgary, Calgary, Alberta, Canada.
Journal:Leukemia. 2017 Nov;31(11):2435-2442. doi: 10.1038/leu.2017.111. Epub 2017 Apr 4.

29:Vemurafenib in combination with cobimetinib in relapsed and refractory extramedullary multiple myeloma harboring the BRAF V600E mutation.
Authors:Mey UJM, Renner C, von Moos R
Institution:Medical Oncology and Hematology, Kantonsspital Graubuenden, Chur, Switzerland.
Journal:Hematol Oncol. 2017 Dec;35(4):890-893. doi: 10.1002/hon.2353. Epub 2016 Sep 19.

30:Bone mineral density utilization in patients with newly diagnosed multiple myeloma.
Authors:Muchtar E, Dagan A, Robenshtok E, Shochat T, Oniashvili N, Amitai I, Raanani P, Magen H
Institution:Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah-Tikva, Israel. Petah Tikva, Israel. Israel. Medical Center, Petah-Tikva, Israel. Medical Center, Petah-Tikva, Israel. Medical Center, Petah-Tikva, Israel.
Journal:Hematol Oncol. 2017 Dec;35(4):703-710. doi: 10.1002/hon.2303. Epub 2016 Jun 21.

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