Skip to main content
SpringerLink
Log in

Treatment of MM: Upcoming Novel Therapies

  • Chapter
  • First Online:
Plasma Cell Dyscrasias

Part of the book series: Cancer Treatment and Research ((CTAR,volume 169))

  • 2456 Accesses

Abstract

Treatment for myeloma has dramatically changed over the past decade, as has overall survival, due in large part to the development of new targeted agents. While proteasome inhibitors and immunomodulatory agents have contributed to improved outcomes, additional new options remain an unmet medical need. Classes of emerging agents include those targeting epigenetics, such as histone deacetylase inhibitors, monoclonal antibodies, and other emerging targets, such as kinesin spindle protein (KSP) inhibitors, cyclin dependent kinase (CDK) inhibitors, and nuclear protein export inhibitors. Future treatment approaches will need to identify how and when to incorporate these treatment options to optimally treat patients with relapsed or refractory myeloma.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lonial S, Mitsiades CS, Richardson PG (2011) Treatment options for relapsed and refractory multiple myeloma. Clin Cancer Res Official J Am Assoc Cancer Res 17(6):1264–1277

    Article  Google Scholar 

  2. Nooka AK, Kastritis E, Dimopoulos MA, Lonial S (2015) Treatment options for relapsed and refractory multiple myeloma. Blood 125(20):3085–3099

    Article  CAS  PubMed  Google Scholar 

  3. Chauhan D, Tian Z, Zhou B et al (2011) In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res 17(16):5311–5321

    Google Scholar 

  4. Richardson PG, Baz R, Wang M et al (2014) Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients. Blood 124(7):1038–1046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kumar SK, Bensinger WI, Zimmerman TM et al (2014) Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood 124(7):1047–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kumar SK, Berdeja JG, Niesvizky R et al (2014) Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol 15(13):1503–1512

    Article  CAS  PubMed  Google Scholar 

  7. Richardson P, Rosenbaum CA, Htut M et al (2013) Twice-weekly oral MLN9708 (Ixazomib Citrate), An investigational proteasome inhibitor, in combination with Lenalidomide (Len) and dexamethasone (Dex) in patients (Pts) with newly diagnosed multiple myeloma (MM): final phase 1 results and phase 2 data. Blood 122(21):535

    Google Scholar 

  8. Ghobrial I, Kaufman JL, Siegel DS et al (2013) Clinical profile of single-agent modified-release oprozomib tablets in patients (Pts) with hematologic malignancies: updated results from a multicenter, open-label, dose escalation phase 1b/2 study. ASH Annula Meeting Abstracts. 2013-11-15 00:00:00 2013;122(21):3184

    Google Scholar 

  9. Kaufman JL, Fabre C, Lonial S, Richardson PG (2013) Histone deacetylase inhibitors in multiple myeloma: rationale and evidence for their use in combination therapy. Clin Lymphoma Myeloma Leuk 13(4):370–376

    Article  CAS  PubMed  Google Scholar 

  10. Richardson PG, Wolf J, Jakubowiak A et al (2011) Perifosine plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with bortezomib: results of a multicenter phase I/II trial. Clin Cancer Res Official J Am Assoc Cancer Res 29(32):4243–4249

    CAS  Google Scholar 

  11. Wolf JL, Siegel D, Goldschmidt H et al (2012) Phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed/refractory multiple myeloma. Leukemia Lymphoma 53(9):1820–1823

    Article  CAS  PubMed  Google Scholar 

  12. Berdeja JG, Hart LL, Mace JR et al (2015) Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Haematologica 100(5):670–676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hideshima T, Cottini F, Ohguchi H et al (2015) Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma. Blood Cancer J 5:e312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Qian DZ, Kato Y, Shabbeer S et al (2006) Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res 12(2):634–642

    Google Scholar 

  15. San-Miguel JF, Richardson PG, Günther A et al (2013) Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and refractory multiple myeloma. J Clin Oncol October 10, 2013 2013;31(29):3696–3703

    Google Scholar 

  16. Richardson PG, Schlossman RL, Alsina M et al (2013) PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood 122(14):2331–2337

    Article  CAS  PubMed  Google Scholar 

  17. Richardson PG, Hungria VTM, Yoon S-S et al (2014) 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. ASCO Meeting Abstracts 32(15_suppl):8510

    Google Scholar 

  18. San Miguel J, Hungria VT, Yoon S-S et al (2014) Efficacy and safety based on duration of treatment of panobinostat plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma in the phase 3 panorama 1 study. Blood. 2014-12-06 00:00:00 2014;124(21):4742

    Google Scholar 

  19. Richardson PG, Hungria VTM, Yoon S-S et al (2014) Characterization of the incidence and management of gastrointestinal toxicity in the phase 3 panorama 1 study of panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and ref…. Blood. 2014-12-06 00:00:00 2014;124(21):2120

    Google Scholar 

  20. Raje N, Vogl DT, Hari PN et al (2013) ACY-1215, a selective histone deacetylase (HDAC) 6 inhibitor: interim results of combination therapy with bortezomib in patients with multiple myeloma (MM). Blood 122(21):759

    Google Scholar 

  21. Yee A, Vorhees P, Bensinger WI et al (2013) ACY-1215, a selective histone deacetylase (HDAC) 6 inhibitor, in combination with lenalidomide and dexamethasone (dex), is well tolerated without dose limiting toxicity (DLT) in patients (Pts) with multiple myeloma (MM) at doses demonstrating biologic ac…. Blood 122(21):3190

    Google Scholar 

  22. Santo L, Hideshima T, Kung AL et al (2012) Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 119(11):2579–2589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lonial S, Durie B, Palumbo A, Miguel JS (2015) Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives. Leukemia

    Google Scholar 

  24. Hsi ED, Steinle R, Balasa B et al (2008) CS1 A potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res 14(9):2775–2784

    Google Scholar 

  25. Lonial S, Vij R, Harousseau JL et al (2012) Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol Official J Am Soc Clin Oncol 30(16):1953–1959

    Article  CAS  Google Scholar 

  26. Richardson PG, Jagannath S, Moreau P et al (2012) A Phase 2 study of elotuzumab (Elo) in combination with lenalidomide and low-dose dexamethasone (Ld) in patients (pts) with relapsed/refractory multiple myeloma (R/R MM): updated results. Blood 120(21):202

    Google Scholar 

  27. Jakubowiak A, Offidani M, Pegourie B et al (2015) A randomized phase II study of bortezomib (Btz)/dexamethasone (dex) with or without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Paper presented at: ASCO; June 2015; Chicago, Ill

    Google Scholar 

  28. Lonial S, Dimopoulos M, Palumbo A et al (2015) Elotuzumab therapy for relapsed or refractory multiple myeloma. New Engl J Med 373(7):621–631

    Article  CAS  PubMed  Google Scholar 

  29. Plesner T, Lokhorst H, Gimsing P, Nahi H, Lisby S, Richardson PG. (2012) Daratumumab, a CD38 monoclonal antibody in patients with multiple myeloma - data from a dose-escalation phase I/II study. ASH Annual Meeting Abstracts 120(21):73

    Google Scholar 

  30. Lokhorst HM, Plesner T, Gimsing P et al (2013) Phase I/II dose-escalation study of daratumumab in patients with relapsed or refractory multiple myeloma. ASCO Meeting Abstracts; 31(15_suppl):8512

    Google Scholar 

  31. Nijhof IS, Noort WA, Lammerts van Bueren J et al (2013) CD38-targeted immunochemotherapy of multiple myeloma: preclinical evidence for its combinatorial use in lenalidomide and bortezomib refractory/intolerant MM patients. 2013;122(21):277

    Google Scholar 

  32. Plesner T, Arkenau T, Lokhorst H et al (2013) Preliminary safety and efficacy data of daratumumab in combination with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma 122(21):1986

    Google Scholar 

  33. Lonial S, Weiss B, Usmani S et al (2015) Phase II study of daratumumab (DARA) monotherapy in patients with ≥ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). Paper presented at: ASCO; June 2015; Chicago,Ill

    Google Scholar 

  34. Deckert J, Wetzel MC, Bartle LM et al (2014) SAR650984, a novel humanized cd38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other cd38 + hematologic malignancies. Clin Cancer Res Official J Am Assoc Cancer Res 20(17):4574–4583

    Article  CAS  Google Scholar 

  35. Martin TG III, Strickland SA, Glenn M, Zheng W, Daskalakis N, Mikhael JR (2013) SAR650984, a CD38 monoclonal antibody in patients with selected CD38 + hematological malignancies- data from a dose-escalation phase I study. ASH Annu Meet Abs 122(21):284

    Google Scholar 

  36. Kumar SK, LaPlant B, Chng WJ et al (2015) Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood 125(3):443–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Niesvizky R, Badros AZ, Costa LJ et al (2015) Phase 1/2 study of CDK4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. Leukemia Lymphoma 1–21

    Google Scholar 

  38. Schmidt J, Braggio E, Kortuem KM et al (2013) Genome-wide studies in multiple myeloma identify XPO1/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276. Leukemia 27(12):2357–2365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365 Clifton Rd, Building C, Room 4004, Atlanta, GA, 30322, USA

    Sagar Lonial

Authors
  1. Sagar Lonial
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sagar Lonial .

Editor information

Editors and Affiliations

  1. Dept. of Medical Oncolgy/Hematology,, ASST-Spedali Civili di Brescia Dept. of Medical Oncolgy/Hematology,, Brescia, Brescia, Italy

    Aldo M. Roccaro

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Irene M. Ghobrial

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Lonial, S. (2016). Treatment of MM: Upcoming Novel Therapies. In: Roccaro, A., Ghobrial, I. (eds) Plasma Cell Dyscrasias. Cancer Treatment and Research, vol 169. Springer, Cham. https://doi.org/10.1007/978-3-319-40320-5_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-40320-5_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-40318-2

  • Online ISBN: 978-3-319-40320-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation