We have discussed the ECOG-ACRIN trial in the past on the website in several posts, including an interview with its principal investigator, Dr. Tait Shanafelt.
It is arguably the most important research presented at the ASH (American Society of Hematology) 2018 Annual Meeting and Congress and deserves revisiting.
Dr. Neil Kay of Mayo Clinic, Rochester, MN, a co-investigator and I discuss why this paper has received so much attention and why it is so important.
- This was a large Phase III trial for frontline CLL patients < 70 years old who needed treatment and were not 17p deleted.
- It compared the gold standard chemo-immunotherapy (CIT) of fludarabine, cyclophosphamide and rituximab (FCR) to Ibrutinib and rituximab (IR).
- 529 patients were accrued between January 31, 2014 and June 9, 2016. 354 patients were assigned to ibrutinib and rituximab (IR) and 175 to FCR.
- IR was superior to FCR for both progression free survival (PFS) and overall survival (OS).
- IR was superior to FCR regardless of age, gender, disease stage, or the presence or absence of 11q deletion.
- IR was also superior to FCR for IGVH unmutated patients but not IGVH mutated patients, the group of CLL patients with whom we know that FCR is most likely to give the best and most durable results.
The trial is so important that we keep returning to see if there is more information that we can squeeze out of the data. Dr. Kay does have a different take on a few items, most notably whether the addition of rituximab adds oomph to ibrutinib when used in this group of patients frontline.
The bottom line for me remains that when we have such a big and well- designed trial that proves patients under 70 years old both live longer and progress later with an ibrutinib based therapy compared to the best CIT, namely FCR, there is no longer any good rationale to treat CLL with chemo-immunotherapy, with the possible rare exception of the younger healthy IGVH mutated patients. And even that is questionable.
Here is my ASH 2018 interview with Dr. Kay.
Here is the http://www.bloodjournal.org/content/132/Suppl_1/LBA-4 if you want to read the original research.
Here is my interview with the lead author, Dr. Shanafelt on the same trial.
Here is a European perspective on this research from my ASH 2018 interview with Dr. Stephan Stilgenbauer.
Here is my commentary on the news coverage around it with a link to the CNN coverage and the New England Journal of Medicine publication.
I told you this was a big deal.
Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.