Authored by Dr. Brian Koffman
The Bottom Line:
For most CLL (chronic lymphocytic leukemia) patients who have received six years of continuous ibrutinib treatment, the levels of residual disease decrease or remain stable for the subsequent 6-12 months after stopping ibrutinib.
Who Performed the Research and Where Was it Presented:
Andy Rawstron, PhD from Leeds, UK, and colleagues presented the results at iwCLL 2023 (international workshop on CLL) in Boston, MA.
Background:
Bruton’s tyrosine kinase inhibition (BTKi), including ibrutinib (IBR), has significantly improved progression-free survival (PFS) in CLL. Usually, IBR is typically given as continuous therapy. However, treatment resistance or side effects can develop. There is reason to hope that intermittent treatment may lower those issues. It is also encouraging to note that in those patients who stop IBR due to toxicity, the median PFS is about two years from discontinuation. What happens when treatment is discontinued in CLL patients who are continuing to do well on IBR is not known because it is not usually discontinued in those circumstances. This study was designed to assess the disease kinetics of disease after treatment is stopped in those who have been treated with IBR for six years and are still responding.
Methods and Participants:
The research looked at 172 participants treated with IBR in the FLAIR trial who had a baseline evaluation before May 3, 2017, to be followed for at least seven years (6 years of treatment and one year of follow-up).
Results:
- 112 participants stopped ibrutinib at the end of treatment (EoT) of 72 months.
- Disease dynamics were studied based on the level of residual CLL in the peripheral blood at EoT.
- 15/112 (12%) had achieved uMRD4 in the blood at EoT:
- All maintained uMRD4 in the blood at six months (10/15 evaluable) and 12 months (13/15 evaluable) after EoT.
- 41/112 (37%) had very low level of disease but not quite uMRD4 with 0.01-1% disease at EoT.
- At 12 months after EoT:
- 6/41 converted to uMRD4.
- 20/41 maintained 0.01-1% disease.
- 5/41 had disease levels increasing to >1% (2/5 with >10% disease) at 12 months after EoT.
- 40/112 (36%) had 1-10% disease at EoT:
- At 12 months after EoT:
- 1/40 converted to uMRD4.
- 7/40 decreased CLL cells to 0.01-1%.
- 14/40 maintained 1-10% disease.
- 8/40 developed >10% disease of which 1/8 showed progressive lymphadenopathy.
- 16/112 (14%) participants had >10% disease at EoT.
- At 12 months after EoT:
- 2/12 decreased CLL cells to 1-10%.
- 4/12 had stable >10% disease.
- 5 had evidence of disease progression at 12 months after EoT.
- Although disease progression was primarily seen in those with >10% disease at the end of treatment, the percent of CLL patients with stable disease over the year was the same in all groups regardless of the level of disease at EoT.
Conclusions:
In most CLL patients who have received six years of ibrutinib, the levels of residual disease decrease or remain stable for the subsequent 6-12 months after stopping ibrutinib. How much is real disease control off therapy and how much is due to redistribution of cells from the bloodstream to the lymph nodes and bone marrow will only be answered by longer follow-up. However, the pleasantly surprising stability of disease levels after treatment cessation supports the safety and advisability of testing an intermittent treatment strategy to determine whether this approach could potentially reduce treatment-emergent resistance and forces us to at least research and reassess the dogma of treating with BTKis until progression or intolerance.
Links and Resources:
Watch Dr. Brian Koffman’s monologue on the abstract:
Stay strong. We are all in this together.
Brian Koffman MDCM (retired), MS Ed
Co-Founder, Executive VP, and Chief Medical Officer
CLL Society
