ASH 2018: Dr. Nicole Lamanna on combination therapies in CLL (chronic lymphocytic leukemia)

Dr. Nicole Lamanna of Columbia University Irving Medical Center is a leading CLL researcher who gives us her broad overview of the important CLL research presented at ASH (American Society of Hematology) Annual Meeting and Exhibition 2018 in San Diego.

Rather than detail all the individual abstracts as we have been doing and will continue to do in upcoming posts, I asked Dr. Lamanna to share her overall Gestalt on the progress reported at this ASH for chronic lymphocytic leukemia patients.

Take Aways:

• Only about 7 years ago at ASH 2011, also in San Diego, CLL therapy was being revolutionized with the introduction of new oral target therapies such as ibrutinib and idelalisib that block the B-cell receptor (BCR).
• Since then venetoclax that targets BCL-2, new monoclonal antibodies, and next generation BCR inhibitors have been approved or are in development.
• These drugs have improved survival for CLL patients, usually when used alone.
• Now at ASH 2018 and other hematology meetings the thrust of research in CLL is moving towards combination therapies using these novel agents that can be stopped after a certain period of time.
• There are multiple combinations in trials. A partial list includes:
  • Venetoclax with ibrutinib (CAPTIVATE and CLARITY)
  • Venetoclax with rituximab (MURANO)
  • Venetoclax with obinutuzumab (CLL14- not presented at ASH but recently announced)
  • FCR and ibrutinib
  • FCR and duvelisib
  • Venetoclax and duvelisib
  • Acalabrutinib, venetoclax, and obinutuzumab
  • Ublituximab (TG-11010), Umbralisib, and Pembrolizumab

• There are many other similar and several different trials and this is just a partial list but it represents a sea change in how CLL treatment is being investigated and how it will likely be treated in the future.
• The results in these trials are very encouraging across the board and in the case of the CLL14 trial led to the approval of venetoclax with obinutuzumab as frontline therapy.
• There are many unanswered questions:
  • What is the best combination or sequencing of drugs for different patient groups?
  • Is there still a role for chemo-immunotherapy such as FCR as part of these combinations?
  • When do we stop the drugs?
    • After a fixed period of time?
    • When we achieve U-MRD in the peripheral blood? I vote for this, but we need the proof.
    • When we achieve U-MRD in the bone marrow?
  • What options do we have if we relapse?

Please enjoy Dr. Lamanna’s interview from ASH 2018:

As she says: “It’s real time for a lot of hope.”