Therapy Trends KOL Insight: Multiple Myeloma [2019]

How will the multitude of emerging combination regimens pan out in MM?

Multiple myeloma treatment is rapidly evolving and the range of combination regimens is set to diversify. Janssen’s Darzalex has already proven a major success story, but what further opportunities await and how will BMS’ Empliciti and Sanofi’s isatuximab fit in? With Celgene’s Revlimid now considered a gold standard of care, and its follow-on agent Pomalyst/Imnovid gaining traction in the first-relapse setting, KOLs discuss the potential future growth and positioning of these IMiDs. Clarity is also offered on the evolving roles of the proteasome inhibitors Kyprolis (carfilzomib; Amgen) and Ninlaro (ixazomib; Takeda). Moreover, could the current excitement surrounding BCMA targeting agents translate to success for CAR-T therapy, BiTEs or ADCs?

Twelve of the world’s foremost KOLs from the US and EU offer candid insights on six marketed therapies and eight pipeline drugs.

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• The table of contents >
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• Review an extract from the report - 1 drug profile >

• With Darzalex and Empliciti already approved for myeloma and isatuximab in late stage development, what differentiates these mAbs and how will they compete with each other?
• As the first and only available orally administered proteasome inhibitor, how does Ninlaro fit within the current treatment paradigm? And how do KOLs perceive this therapy in comparison with established PI therapies Velcade and Kyprolis?
• Phase III ALCYONE, MAIA and CASSIOPEIA trails are investigating Darzalex in combination with other agents in the front-line setting. How do KOLs view these trials and their potential to shape the future outlook for Darzalex?
• In the US, fast-track review of selinexor has been revoked as a result of adverse events, giving the FDA more time to review the data. How concerned are KOLs regarding selinexor’s toxicity profile and what impact is this expected to have on the likely success of the product?
• Legend/Janssen, bluebird bio/Celgene, GlaxoSmithKline and Amgen are all developing anti-BMCA approaches to the treatment of myeloma. How do KOLs view the relative merits of CAR-T therapy, BiTEs and ADCs and where could they play a role?
• AbbVie/Genentech’s Bcl-2 inhibitor, venetoclax, demonstrates potent activity in t(11;14) translocated MM. But how optimistic are KOLs regarding its future in MM given the serious safety concerns that emerged from the BELLINI trial?

“We're still riding that wave of daratumumab everywhere, adding daratumumab upfront, adding daratumumab in smoldering, and then likely in the next three to five years we need something post-daratumumab, because those patients are not being cured.”
US Key Opinion Leader

“BiTE is much simpler than CAR-T cells, we don’t need to wait weeks to obtain the drugs, and it’s cheaper. There is some toxicity, but that is also the case with CAR-T. So, will the future be BiTE or CAR-T cells? We don't really know, but I believe that this approach will have a future.” 
US Key Opinion Leader

Marketed Therapies

• Revlimid (lenalidomide; Celgene)
• Pomalyst/Imnovid (pomalidomide; Celgene)
• Kyprolis (carfilzomib; Amgen)
• Ninlaro (ixazomib; Takeda)
• Darzalex (daratumumab; Janssen)
• Empliciti (elotuzumab; BMS)

Preregistration/Phase III Therapies

• Isatuximab (Sanofi)
• Selinexor (Karyopharm)
• Venetoclax (Venclexta/Venclyxto; AbbVie/Genentech)
  

Phase I/II Therapies

• CAR-T cell therapies (bb 2121 and bb 21217; Bluebird Bio/Celgene)
• JNJ-68284528 (LCAR-B38M; Legend/Janssen)
• GSK2857916 (GSK)
• AMG 420  (Amgen)

KOLs from North America

• Irene Ghobrial, Professor of Medicine, Dana Farber Cancer Institute, Boston, MA
• Carol Ann Huff, Associate Professor of Oncology, Director, Myeloma Program, Division of Hematologic Malignancies, Johns Hopkins University School of Medicine, Baltimore, MD
• Joseph Mikhael, Professor at the Translational Genomics Research Institute (TGen) and Chief Medical Officer of the International Myeloma Foundation, Phoenix, AZ
• Roger Pearse, Associate Professor of Medicine, Weill Cornell Medical College, New York, NY
• Paul G. Richardson, Professor of Hematology, Harvard Medical School, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA
• Ravi Vij, Professor of Medicine, Oncology Division, Washington University School of Medicine, St. Louis, MO

KOLs from Europe

• Mario Boccadoro, Professor of Haematology, University of Torino, Piemont, Turin, Italy
• 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
• Alberto Rocci, Consultant Haematologist at Manchester Royal Infirmary, Honorary Senior Lecturer at the University of Manchester, Manchester, UK
• Philippe Rodon, Associate Professor of Oncology, Centre Hospitalier Périgueux, Périgueux, France
• Anonymous KOL, Assistant Professor of Medicine (Hematology and Oncology) at a major university hospital, Germany

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