Multiple Myeloma: KOL Insight [2018]

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Publication Date:
June 2018
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How do the multitude of emerging combination regimens stack up in MM?

The treatment of multiple myeloma (MM) is rapidly evolving and the range of combination therapies is set to diversify with triplet and quadruple regimens being increasingly used. With Celgene’s Revlimid entrenched in multiple settings, what threats and opportunities lie ahead? Could Revlimid’s dominance in the maintenance setting following ASCT be challenged by Darzalex (Genmab/Janssen Biotech) or Ninlaro (Takeda)? Takeda/Janssen’s Velcade is well established in both frontline and relapsed settings, but could its positioning be usurped by Amgen’s Kyprolis or Ninlaro? And how do KOLs see the roles of the mAbs Darzalex (Genmab/Janssen Biotech), Empliciti (AbbVie/BMS) and Sanofi/Immunogen’s isatuximab developing? Moreover, will the current excitement surrounding Bluebird Bio/Celgene’s CAR-T cell therapies translate into clinical success?

Twelve of the world’s leading KOLs from the US and Europe offer candid insights on seven marketed therapies and seven Phase II/III drugs.

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Top takeaways

  • How is the first-line treatment of MM expected to evolve? With a number of companies investing in multiple combination regimens, who could emerge victorious?
  • Monoclonal antibodies represent the newest class of therapies to be approved for MM. How are these products changing the treatment paradigm?To what extent are they currently used and what is their potential?
  • Celgene’s Revlimid is firmly entrenched in multiple settings. But what threats and opportunities lie ahead?
  • Takeda/Janssen’s Velcade is well established in both frontline and relapsed settings.  But could next-generation proteasome inhibitors, Amgen’s Kyprolis or Takeda’s Ninlaro, challenge the status quo?
  • CAR-T therapies have been touted as potentially ‘game changing’ for MM. But do KOL anticipate thattheir therapeutic benefit will live up to expectations, and outweigh safety and cost concerns?
  • Immunomodulatory agents Revlimid and Pomalyst/Imnovid are pillars of MM therapy. How do KOLs see the use of these agents evolving in the future treatment paradigm?
  • AbbVie/Genentech’s Bcl-2 inhibitor, venetoclax, demonstrates potent activity in a subgroup of patients with a well-defined genetic abnormality. How optimistic are KOLs with regard to the first potential targeted therapy in MM?
  • The FDA has granted Karyopharm’s SINE therapy, selinexor, Fast Track designation. How do KOLs perceive this first-in-class product, based on interim results from the Phase IIb STORM study?
  • Smoldering multiple myeloma is currently not a target for pharmaceutical intervention.  With a Phase III study currently ongoing, how do KOLs view the potential for Genmab/Janssen’s Darzalex to be used in this setting?
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“There are a lot of studies using proteasome inhibitors, IMiDs and mAbs upfront. These studies are in progress and in the next one to two years, we'll have the results and we’ll have market authorisation. For sure, the treatment will change.”
US Key Opinion Leader

“The use of CAR-T cells in the late/advanced stage of MM in patients who are refractory to everything, achieved a complete response and even minimal residual disease. This is critical. This will probably dramatically change the landscape of treatment for myeloma.” 
US Key Opinion Leader

“Darzalex and isatuximab were basically neck and neck at the very origin. The makers of Darzalex proved unequivocally how to bring a drug to market and have shut out isatuximab from the whole of the market.”
US Key Opinion Leader

Sample of therapies covered

Marketed Therapies

  • Revlimid (lenalidomide; Celgene)
  • Pomalyst/Imnovid (pomalidomide; Celgene)
  • Kyprolis (carfilzomib; Onyx [Amgen])
  • Ninlaro (ixazomib; Takeda)
  • Darzalex (daratumumab; Genmab/Janssen Biotech)
  • Empliciti (elotuzumab; AbbVie/BMS)
  • Farydak (panobinostat; Novartis)

Phase III Therapies

  • Isatuximab (Sanofi/ImmunoGen)
  • Venetoclax (Venclexta/Venclyxto; AbbVie/Genentech)
  • Plitidepsin (Aplidin; PharmaMar)
  • Selinexor (KPT-330; Karyopharm Therapeutics)
  • Opdivo (nivolumab; Bristol-Myers Squibb)
  • JNJ-63723283 (Janssen)

Phase II Therapies

  • CAR-T cell therapies (e.g. bb 2121 and bb 21217; Bluebird Bio/Celgene)

KOLs interviewed

KOLs from North America

  • Kenneth C. Anderson, Kraft Family Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA
  • Carol Ann Huff, Associate Professor of Medicine and Oncology, Director, Myeloma Program, Division of Hematologic Malignancies, Johns Hopkins University School of Medicine, Baltimore, MD
  • Joseph Mikhael, Chief Medical Officer, International Myeloma Foundation Adjunct Professor, Arizona State University, College of Health Solutions, North Hollywood, CA
  • Roger Pearse, Associate Professor of Medicine, Weill Cornell Medical College, New York, NY
  • Paul G. Richardson, Professor of Medicine, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
  • Ravi Vij, Professor of Medicine, Oncology Division, Washington University Medical School, St. Louis, MO

KOLs from Europe

  • Joan Blade, Professor of Medicine, University of Torino, Piemont, Turin, Italy
  • Mario Boccadoro, Professor of Medicine, University of Torino, Piemont, Turin, Italy
  • Thierry Facon, Professor of Medicine, Lille University Hospital, Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France
  • Heinz Ludwig, Professor/Director of the Wilhelminen Cancer Research Institute, Department of Medicine, Center for Oncology, Haematology and Palliative Care, Wilhelminen Hospital, Vienna, Austria
  • María-Victoria Mateos, Professor of Medicine, Hospital Universitario de Salamanca, Salamanca, Spain
  • Philippe Moreau, Professor of Clinical Haematology/Head of Haematology Department, University Hospital Hotel Dieu, Nantes, France

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