Multiple Myeloma
February 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: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.

2: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.

3:Immunoparesis in newly diagnosed Multiple Myeloma patients: Effects on overall survival and progression free survival in the Danish population.
Authors:Sorrig R, Klausen TW, Salomo M, Vangsted AJ, Frolund UC, Andersen KT, Klostergaard A, Helleberg C, Pedersen RS, Pedersen PT, Helm-Petersen S, Teodorescu EM, Preiss B, Abildgaard N, Gimsing P
Institution:Department of Hematology, Rigshospitalet, Copenhagen, Denmark. University of Copenhagen, Copenhagen, Denmark. Denmark. Holsterbro, Denmark.
Journal:PLoS One. 2017 Dec 7;12(12):e0188988. doi: 10.1371/journal.pone.0188988. eCollection 2017.

4:Pooled analysis of the reports of carfilzomib/ixazomib combinations for relapsed/refractory multiple myeloma.
Authors:Xu W, Sun X, Wang B, Guo H
Institution:Department of Hematology, Weifang People's Hospital, Weifang, China.
Journal:Ann Hematol. 2018 Feb;97(2):299-307. doi: 10.1007/s00277-017-3173-9. Epub 2017 Nov 20.

5: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.

6:Drug response prediction in high-risk multiple myeloma.
Authors:Vangsted AJ, Helm-Petersen S, Cowland JB, Jensen PB, Gimsing P, Barlogie B, Knudsen S
Institution:Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: Denmark. Denmark; Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark. Copenhagen, Denmark.
Journal:Gene. 2018 Feb 20;644:80-86. doi: 10.1016/j.gene.2017.10.071. Epub 2017 Nov 6.

7: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.

8: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.

9: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.

10: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.

11: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.

12: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.

13: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.

14: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.

15: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.

16:Infectious complications in multiple myeloma receiving autologous stem cell transplantation in the past 10 years.
Authors:Park H, Youk J, Kim HR, Koh Y, Kwon JH, Yoon SS, Park S, Choe PG, Kim NJ, Oh MD, Park WB, Kim I
Institution:Division of Hematology/Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehag-ro, Jongno-gu, Seoul, 03080, Republic of Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.; Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.; Department of Internal Medicine, ChungBuk National University College of Medicine, Cheongju, Chungchungbuk-do, Republic of Korea.; Division of Infectious Diseases, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehag-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Journal:Int J Hematol. 2017 Dec;106(6):801-810. doi: 10.1007/s12185-017-2313-2. Epub 2017 Aug 20.

17: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.

18:Efficacy of daratumumab-based therapies in patients with relapsed, refractory multiple myeloma treated outside of clinical trials.
Authors:Lakshman A, Abeykoon JP, Kumar SK, Rajkumar SV, Dingli D, Buadi FK, Gonsalves WI, Leung N, Dispenzieri A, Kourelis TV, Go RS, Lacy MQ, Hobbs MA, Lin Y, Warsame R, Lust J, Fonder AL, Hwa YL, Hayman SR, Russell SJ, Kyle RA, Gertz MA, Kapoor P
Institution:Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Journal:Am J Hematol. 2017 Nov;92(11):1146-1155. doi: 10.1002/ajh.24883. Epub 2017 Sep 8.

19: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.

20:Meeting report of the 6th Heidelberg Myeloma Workshop: current status and developments in diagnosis and therapy of multiple myeloma.
Authors:Merz M, Raab MS, Goldschmidt H, Hillengass J
Institution:Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany. Neuenheimer Feld 410, 69120, Heidelberg, Germany. Research Center, Heidelberg, Germany. Neuenheimer Feld 410, 69120, Heidelberg, Germany. Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Journal:J Cancer Res Clin Oncol. 2017 Dec;143(12):2521-2526. doi: 10.1007/s00432-017-2463-x. Epub 2017 Jun 26.

21: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.

22:Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes.
Authors:Hari P, Mateos MV, Abonour R, Knop S, Bensinger W, Ludwig H, Song K, Hajek R, Moreau P, Siegel DS, Feng S, Obreja M, Aggarwal SK, Iskander K, Goldschmidt H
Institution:Medical College of Wisconsin, Milwaukee, WI, USA. Columbia, Canada. Ostrava, Czech Republic. Ostrava, Czech Republic.
Journal:Leukemia. 2017 Dec;31(12):2630-2641. doi: 10.1038/leu.2017.122. Epub 2017 Apr 25.

23:Efficacy and safety of high-dose chemotherapy with autologous stem cell transplantation in senior versus younger adults with newly diagnosed multiple myeloma.
Authors:Huang LW, Bacon W, Cirrincione C, Peterson B, Long G, Rizzieri D, Sullivan KM, Corbet K, Horwitz M, Chao N, Gasparetto C, Tuchman SA
Institution:Department of Internal Medicine, Duke University Medical Center, Durham, NC, USA. Institute, Durham, NC, USA. Durham, NC, USA. Durham, NC, USA. Institute, Durham, NC, USA. Institute, Durham, NC, USA. Institute, Durham, NC, USA. Institute, Durham, NC, USA. Institute, Durham, NC, USA. Institute, Durham, NC, USA. Institute, Durham, NC, USA.
Journal:Hematol Oncol. 2017 Dec;35(4):752-759. doi: 10.1002/hon.2379. Epub 2017 Jan 19.

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