ASH 2017: Dr. Richard Furman on the importance of MCL-1 in CLL (chronic lymphocytic leukemia)
Combinations of potent medications are the future in CLL. At the American Society of Hematology (ASH) Annual Meeting and Exposition in snowy Atlanta, 2017, several promising combinations were discussed.
Dr. Matt Davids at Dana Farber Cancer Institute, Harvard Medical School has combined the most potent chemo-immunotherapy, FCR (fludarabine, cyclophosphamide, and rituximab) with the powerful novel agent ibrutinib in frontline therapy with remarkable results in chronic lymphocytic leukemia.
Take Aways:
- FCR on its own has high response rates frontline in CLL and has allowed some patients after 6 months of therapy to remain disease free for 15 years. It is reasonable to suggest that this small subset of patients have been cured of their CLL.
- FCR is best restricted to young fit patients due to its powerful suppression of the immune system and the bone marrow leading to infections, low blood counts and secondary cancers.
- FCR works best on patients who have favorable prognostic markers such as IGHV mutated and no adverse genetic markers. This is the group that tends to have the long deep remissions.
- FCR does not work well on patients with deletion 17p and should not be used on its own for these patients.
- Ibrutinib is a powerful novel oral drug with very high response rates as monotherapy frontline.
- Ibrutinib is not a form of chemotherapy, but rather targets BTK (Bruton’s tyrosine kinase), a pathway critical to the CLL cell’s survival and proliferation.
- Ibrutinib works for all patients whatever their prognostic markers, including deletion 17p.
- The combination of ibrutinib and FCR (iFCR) was used frontline in young fit patients in this clinical trial presented at ASH 2017.
- Overall response rate (ORR) was 100%.
- 82% of the patients were MRD- in the bone marrow (no evidence of any CLL cells looking at 10,000 leukocytes).
- Even 71% of the unmutated patients who usually do not do as well with FCR were MRD- in the marrow.
- Aggressive mandatory management of low blood counts with growth factors and prophylaxis for infections helped limit but not completely prevent serious side effects. There were no deaths in the trial. This is likely due the selection of young fit patients.
Here is the link to the abstract: https://ash.confex.com/ash/2017/webprogram/Paper101497.html
Conclusions:
The depth of response to iFCR is truly amazing and there is good reason to believe this combination will produce very durable response. MRD negativity in the bone marrow is likely a strong predictor of improved survival.
Could we achieve the same success with non-chemo combinations and avoid the risks and toxicities of chemotherapy?
Only time will tell, because what we patients really care about is the progression free survival (PFS) and overall survival (OS).
Enjoy the interview below, or read the transcript here.
Much more from ASH to come.
Brian Koffman, MD 12/19/17
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