Targeted Therapies in CLL – Therapeutic Next Steps

At the April 2015 CLL Patient Education and Empowerment meeting held in conjunction with the CLL Research Consortium meeting at UCSD in San Diego, Dr. William Wierda from MD Anderson Cancer Center wrapped up all the information provided previously about targeted therapies (BCL-2 inhibitors, kinase inhibitors, monoclonal antibodies and high-risk disease) to look towards the future.

Focusing on therapeutic next steps, he provided a comprehensive overview of overall treatment goals for CLL, specifically:

• Cure CLL
  • For eligible patients though allogeneic stem cell transplant
  • For patients with mutated IGVH, some patients have achieved extended remissions lasting over 10 years
• Achieve excellent disease control for most patients through treatment with BCR inhibitors and BCL-2 inhibitors
• Eliminate disease and treatment complications, such as:
  • Infection
  • Auto-immunity
  • 2^nd cancers
  • Secondary cancers (resulting from treatment with alkylating agents)

Dr. Wierda provided a comprehensive review of the current standards of care, considering age and chromosomal abnormalities determined by FISH:

• First-line therapy (for those whose symptoms determine therapy is warranted) for patients who are:
  • Fit and eligible for chemo-immunotherapy
  • Elderly (65 or older)
  • Have Del(17P)
• Treatments for active relapsed or refractory disease
• Richter’s Transformation
• Treatments for infections
  • Antibiotics
  • Growth factor support (for low neutrophils)
  • IVIG (for low IgG)
  • Complete remission (an intact immune system achieved through CR is a treatment for infection)

Dr. Wierda went on to conceptualize and strategize how research should go forward using clearly defined clinical objectives to treat various patient subgroups, such as:

• Elderly/frail
• Younger/fit
• IGHV-mutated (IGVH-M)
• IGHV-unmutated (IGVH-UM)

He wraps up his talk with a review of how the currently available drugs may be used in combinations, or in sequences as a strategy to achieving cure, as well as the roles of including promising new drugs (immune-modulating monoclonal antibodies, new mAbs, cell therapy, pleiotropic pathway modulators and vaccines) in those combinations.

In appreciation, Dr. Wierda closed by acknowledging that no treatment progress is possible without the courageous patient participation on clinical trials and clinical research.

Listen to Dr. Weirda’s thoughtful review of current and future strategies to achieve a cure for CLL

Betsy Dennison, RN  11/19/15