Professor Michael Hallek leads the collaborative CLL German research group from his clinic in Cologne. Among other contributions, the research he led helped established FCR (fludarabine, cyclophosphamide and rituximab) as the “gold standard” therapy for young fit CLL patients with no deletion 17p and functioning TP53, giving us the first therapy that showed it could prolong life for CLL patients.
Now the treatment paradigm is changing and changing fast.
Dr. Hallek outlines two powerful trends in CLL therapy and tackles the questions of the future of chemo-immunotherapy (CIT) for chronic lymphocytic leukemia.
- Papers at ASH 2018 proved that monotherapy with ibrutinib (I) or ibrutinib in combination with rituximab have better progression free survival outcomes for all elderly CLL patients to BR (bendamustine and rituximab (R)) and is also superior to FCR for nearly all young fit patients with the exception of those with the best prognostics, specifically those with the favorable mutated IGHV (immunoglobulin variable heavy chain variable) and no other poor markers.
- For those few favorable mutated patients the outcomes are similar for both BR and the two ibrutinib treatment groups.
- These powerful and somewhat surprising positive results coupled the seven-year ibrutinib data from Dr. Byrd and other research argue strongly for simple single agents as the favored frontline therapy for CLL patients.
- The other big trend at ASH 2018 was combinations of multiple different novel agents such as I plus venetoclax (V) or V plus R or even triplets (V+I + obinutuzumab).
- These offer the promise of being able to stop therapy after a finite time that could potentially provide the following advantages:
- Avoiding continued exposure that eventually might lead to resistance.
- Significant cost savings for patients and health systems.
- Emotional relief from needing to treat our cancer daily.
In my interview at ASH 2018 in San Diego, CA, Dr. Hallek and I debated whether this ASH heralded the end of CIT for nearly all patients. We disagreed.
But we did agree that in the wonderful “battle” between the strong results of chemo free mono and combo therapies for CLL, the future belongs to novel combinations of fixed duration.
ASH showed that the role of CIT is shrinking in CLL. Both therapies with a single novel drug such as ibrutinib and combination of novel drugs offer strong results. Today, we have some very good choices. Tomorrow we should have even more data to help us decide. Whether the best path forward is combinations or sequential use of the great drugs we have will only be worked out with research through clinical trials.
Here is our interview:
Here are links to the two abstracts he referenced. Soon we will be posting our interviews with the lead investigators.
The one on FCR versus Ibrutinib (and rituximab) can be read here:
A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy Vs. Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL): A Trial of the ECOG-ACRIN Cancer
The one on BR versus ibrutinib with or without rituximab can be read here:
Ibrutinib Alone or in Combination with Rituximab Produces Superior Progression Free Survival (PFS) Compared with Bendamustine Plus Rituximab in Untreated Older Patients with Chronic Lymphocytic Leukemia (CLL): Results of Alliance North American Intergroup
These trials are practice changing and we will be revisiting them often.
We are all in this together
Chief Medical Officer and Executive VP, CLL Society