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ASH 2020: Dr. Allan Discusses Front-Line Ibrutinib Treatment for High-Risk Chronic Lymphocytic Leukemia (CLL) Patients

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

In this video, Dr. John N. Allan, M.D., an Assistant Professor of Medicine at Weill Cornell Medicine and a CLL specialist at New York-Presbyterian/Columbia University Irving Medical Center, is interviewed by CLL Society Co-Founder and Chief Medical Officer, Dr. Brian Koffman, M.D., a retired family physician and CLL patient. This video was recorded at the 62nd Annual Meeting of the American Society of Hematology, held virtually in December 2020. 

Historically, before the introduction of targeted agents, patients who have the high-risk variants of deletion (17p) or a P53 mutation have been among the most difficult to treat. These patients are essentially refractory (do not respond) to the chemotherapy or chemoimmunotherapy treatments that were the only approved treatments for chronic lymphocytic leukemia before 2014 when ibrutinib (Imbruvica®) was approved. Remission rates among these high-risk patients were very low, and their disease progressed quickly. In some cases, deletion (17p) or P53 mutated patients saw their CLL become “angrier” after exposure to chemotherapy containing regimens, resulting in poor overall outcomes. 

Ibrutinib, a once-daily oral Bruton’s Tyrosine Kinase (BTK) inhibitor, is the only targeted therapy to demonstrate both a significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized phase III studies in both treatment-naïve (TN) and relapsed or refractory (R/R) CLL / SLL. 

Because there is a lack of long-term follow-up of patients with P53 aberrations, Investigators for this study pooled data from four early clinical trials to look at the long-term durability of response in this high-risk group. P53 “aberrations” include deletion (17p), in which a portion of chromosome 17 is missing, or the P53 gene is mutated. The P53 gene is located on chromosome 17. The P53 gene provides instructions for making a protein called tumor protein p53 (or TP53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way. 

Take-Aways 

  • This study looked at 89 patients with deletion (17p) or P53 mutations who were subjects in four Phase II or Phase III trials, including PCYC-1122eRESONATE-2ILLUMINATE, and ECOG-1912. These studies used ibrutinib as monotherapy or combined with one of the two approved Anti-CD20 monoclonal antibodies (rituximab or obinutuzumab.) 
  • The numbers available for this study are small because once ibrutinib showed superiority to chemoimmunotherapy (CIT), it became unethical to include these high-risk patients in a clinical trial in which they could be randomized to the CIT arm of the study.  
  • Fifty-five percent of chronic lymphocytic leukemia patients in this pooled analysis were deletion (17p), with the remaining forty-five percent having a P53 mutation. 
  • In the overall pooled CLL population, the 4-year PFS rate was 79%. For the 47 patients who had either del(17p) only or TP53 mutation only, median PFS was not reached. For the 11 patients who had both del(17p) and TP53 mutations, the median PFS was 42.8 months. 
  • In the overall pooled population, the 4-year OS rate was 88%  
  • Most patients (83/89) achieved a response resulting in an overall response rate (ORR) of 94%, including 39% who achieved a complete remission (CR). 
  • High-risk patients did not experience a different rate of adverse events compared to those with lesser risk factors. The adverse event rates declined over time with both groups with the highest rates of AEs occurring in the first year. 

Conclusions: 

Although patients with TP53 aberrations remain at risk for progression, first-line treatment with ibrutinib has meaningfully improved the poor prognosis in this high-risk population. 

To learn more about clinical trials in general, go to https://cllsociety.org/clinical-trials 

Thanks for reading this summary and viewing this interview.

Here is the published abstract itself: Long-Term Efficacy of First-Line Ibrutinib Treatment for Chronic Lymphocytic Leukemia (CLL) With 4 Years of Follow-Up in Patients With TP53 Aberrations (del(17p) or TP53 Mutation): A Pooled Analysis From 4 Clinical Trials. 

Stay strong; we are all in this together!

Thomas. E. Henry III, MBA, RPh, CPh

Thomas E. Henry III is a Registered Pharmacist and CLL Patient. He is President and Senior Consultant for Burlington Consulting Associates, a company that provides consulting services to health systems nationwide. Tom is a CLL Society Medical Advisory Board member and strives to educate other CLL patients through his blog https://www.cllpharmacist.com. He has a forty-two-year career as a licensed pharmacist and has served as Chief Pharmacy Officer at two Top-15 Comprehensive Cancer Centers, Moffitt (Tampa, FL) and Roswell Park Cancer Institute (Buffalo, NY).