1. ROBERT ORLOWSKI, MD, PhD
Houston, USA
• Professor, Department of Myeloma/Lymphoma, at the
University of Texas MD Anderson Cancer Center
• Dr. Orlowski has published numerous book chapters,
articles, and abstracts on cancer therapy, with a focus on the
molecular pathogenesis of oncologic disease processes and
the mechanisms of action of chemotherapeutics. His clinical
research efforts focus on the translation of promising
laboratory based findings into novel clinical trials for
patients with hematologic malignancies. He has published
in, and is a reviewer for, several journals, including Blood,
Cancer Research, Journal of Clinical Oncology, and the
New England Journal of Medicine. He has received several
awards, including The Leukemia & Lymphoma Society
Scholar in Clinical Research and the Jefferson-Pilot
Fellowship in Academic Medicine.
2. Recent Updates on Targeted
Therapies for Multiple Myeloma
Robert Z. Orlowski, Ph.D., M.D.
Director, Myeloma Section
Florence Maude Thomas Cancer Research Professor
Departments of Lymphoma/Myeloma & Experimental Therapeutics
Principal Investigator, MD Anderson SPORE in Multiple Myeloma and MD
Anderson Moon Shot in High Risk Myeloma
Chair, SWOG Myeloma Committee
4. 2013 ASH Abstract 285
Prolonged Survival and Improved Response Rates
with ARRY-520 in Relapsed/Refractory Multiple
Myeloma (RRMM) Patients with Low -1 Acidα
Glycoprotein (AAG) Levels : Results From a Phase 2
Study
Sagar Lonial, Jatin J. Shah, Jeffrey Zonder, William I. Bensinger, Adam D. Cohen,
Jonathan L. Kaufman, Ajay K. Nooka, Donna M. Weber, Brandi Hilder, Selena A.
Rush, Ann Ptaszynski, Duncan Walker, and Robert Z. Orlowski
9. 2013 ASH Abstract 1982
Phase 1 Study of the Novel Kinesin Spindle Protein
Inhibitor ARRY-520 + Carfilzomib (Car) in Patients
with Relapsed and/or Refractory Multiple Myeloma
(RRMM)
Jatin J. Shah, Lei Feng, Sheeba K. Thomas, Donna M. Weber, Michael Wang,
Brandi Hilder, Raymond Alexanian, and Robert Z. Orlowski
11. Initial Efficacy Data
• All patients were bortezomib-refractory
• 63% achieved an MR or better in this phase I
• Growth factor support was not needed after
cycles 1 and 2
12. 2014 ASH Abstract 3453
Oprozomib and Dexamethasone in Patients with
Relapsed and/or Refractory Multiple Myeloma: Initial
Results from the Dose Escalation Portion of a Phase
1b/2, Multicenter, Open-Label Study
Parameswaran N. Hari, Kenneth H. Shain, Peter M. Voorhees, Nashat Gabrail,
Muneer H. Abidi, Jeffrey Zonder, Ralph V. Boccia, Paul G. Richardson, Linda L.
Neuman, Sandra J. Dixon, and Claudia Paba Prada
13. 2014 ASH Abstract 34
Clinical Profile of Single-Agent Oprozomib in Patients
(Pts) with Multiple Myeloma (MM) : Updated Results
from a Multicenter, Open-Label, Dose Escalation
Phase 1b/2 Study
Ravi Vij, Michael Savona, David S. Siegel, Jonathan L. Kaufman, Ashraf Badros,
Irene M. Ghobrial, Agne Paner, Sundar Jagannath, Andrzej Jakubowiak, Joseph R.
Mikhael, Prashant Kapoor, Linda L. Neuman, Ju RueyJiuan Lee, and Jesus G.
Berdeja
18. 2014 ASH Abstract 301
Phase 1 Study Update of the Novel Pan-Pim Kinase
Inhibitor LGH447 in Patients with Relapsed/
Refractory Multiple Myeloma
Marc S. Raab, Enrique M. Ocio, Sheeba K. Thomas, Andreas Günther, Yeow-Tee
Goh, Daniel Lebovic, Andrzej Jakubowiak, Dongweon Song, F. Xiang, Apurva Patel,
K. Gary Vanasse, and Shaji Kumar
20. Study Design
• Primary endpoint: MTD/RP2D
• Secondary endpoints: safety, tolerability, preliminary anti-
myeloma activity, pharmacodynamics, pharmacokinetic
profile
Dose Escalation Dose Expansion
MTD/RDE
Relapsed and/or refractory
MM
LGH447 daily, oral
≈ 12 patients
Relapsed and/or
refractory MM
LGH447 daily, oral
70m
g
150m
g
200m
g
250m
g
350m
g
300m
g
500m
g
700m
g
400m
g
21. Safety
AEs Suspected
Related to Study
Drug Gr 3/4, n (%)
Total
N = 59
Thrombocytopenia 18 (30.5)
Neutropenia 11 (18.6)
WBC decreased 9 (15.2)
Anemia 8 (13.6)
Fatigue 7 (11.9)
Lymphopenia 5 (8.5)
Diarrhea 3 (5.1)
Hyperglycemia 3 (5.1)
Hypophosphatemia 3 (5.1)
• The MTD was 500 mg once
daily
• 10 DLTs: thrombocytopenia
most common (1 pt each @
200-, 250-, 350-, 400-, & 500-
mg); fatigue @ higher doses
(500 & 700 mg)
• Grade 3/4 AEs were mostly
hematologic
• No deaths on study
22. Efficacy Data
• ORR: 10.5%; CBR: 21.1%; DCR: 71.9%
• Median duration of response was 23.0 weeks
23. 2014 ASH Abstract 31
Ibrutinib, Single Agent or in Combination with
Dexamethasone, in Patients with Relapsed or
Relapsed/Refractory Multiple Myeloma (MM) :
Preliminary Phase 2 Results
Ravi Vij, Carol Ann Huff, William I. Bensinger, David S. Siegel, Sundar Jagannath,
Jesus Berdeja, Nikoletta Lendvai, Daniel Lebovic, Larry D. Anderson Jr., Caitlin L.
Costello, Keith E. Stockerl-Goldstein, Jacob P. Laubach, Laurence Elias, Fong Clow,
Maria Fardis, Thorsten Graef, Elizabeth Bilotti, and Paul G. Richardson
27. 2014 ASH Abstract 302
Final Results for the 1703 Phase 1b/2 Study of
Elotuzumab in Combination with Lenalidomide and
Dexamethasone in Patients with Relapsed/Refractory
Multiple Myeloma
Paul G. Richardson, Sundar Jagannath, Philippe Moreau, Andrzej Jakubowiak, Marc S.
Raab, Thierry Facon, Ravi Vij, Darrell White, Donna E. Reece, Lotfi Benboubker, Jeffrey
Zonder, L. Claire Tsao, Kenneth C. Anderson, Eric Bleickardt, Anil K. Singhal, and Sagar
Lonial
33. 2014 ASH Abstract 84
Safety and Efficacy of Daratumumab with
Lenalidomide and Dexamethasone in Relapsed or
Relapsed, Refractory Multiple Myeloma
Torben Plesner, Hendrik-Tobias Arkenau, Henk M. Lokhorst, Peter Gimsing, Jakub
Krejcik, Charlotte Lemech, Monique C. Minnema, Ulrik Lassen, Jacob P. Laubach,
Tahamtan Ahmadi, Howard Yeh, Mary E. Guckert, Huaibao Feng, Nikolai
Constantin Brun, Steen Lisby, Linda Basse, Antonio Palumbo, and Paul G.
Richardson
41. 2014 ASH Abstract 83
A Phase Ib Dose Escalation Trial of SAR650984 (Anti-
CD-38 mAb) in Combination with Lenalidomide and
Dexamethasone in Relapsed/Refractory Multiple
Myeloma
Thomas G. Martin III, Rachid Baz, Don M. Benson Jr., Nikoletta Lendvai, Frank
Campana, Eric Charpentier and Ravi Vij
46. Conclusions
• Oral proteasome inhibitors are moving forward
that will improve patient convenience
• Small molecules targeting new pathways are
showing efficacy, and are in registration studies
• Monoclonal antibodies recognizing myeloma
surface antigens may soon achieve regulatory
approvals
• Additional studies are needed to understand how
these new tools can best be incorporated into our
armamentarium against myeloma