iwCLL 2021 | Refining standard treatment approaches for CLL
Paolo Ghia, MD, PhD, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy, discusses strategies to refine standard treatment approaches for chronic lymphocytic leukemia (CLL), outlining key studies of interest. Dr Ghia explains that the new genetic classification based on immunoglobulin and p53 gene mutation status has replaced previous standards. Strategies are now shifting to a more personalized approach, taking into account a patient’s genetic aberrations, age, fitness and comorbidities. Dr Ghia explains that Bruton’s tyrosine kinase (BTK) inhibitors are now standard of care for patients with p53 mutations and that fixed-duration venetoclax plus obinutuzumab combination therapy is currently considered as the most effective treatment for patients with mutant immunoglobulin genes. Continuous therapy with BTK inhibitors is recommended for patients with no mutations in either of these two genes. This interview took place at the 19th International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Biennial Meeting, held virtually in 2021.
Transcript (edited for clarity)
Here at the iwCLL meeting I had the possibility to speak about, discuss about the standards in CLL, and how we should refine our CLL management and treatment in the light of the new [inaudible] treatment that we have. And indeed, I think that it’s really a very dynamic period.
So, I think that the message that I tried to deliver that we don’t have any more standards. Meaning that in the recent past, we had the FCR, fludarabine, cyclophosphamide and rituximab for the young, fit patients; we had chlorambucil-based treatment for the elderly, unfit; and we had bendamustine-based treatment for those in between...
Here at the iwCLL meeting I had the possibility to speak about, discuss about the standards in CLL, and how we should refine our CLL management and treatment in the light of the new [inaudible] treatment that we have. And indeed, I think that it’s really a very dynamic period.
So, I think that the message that I tried to deliver that we don’t have any more standards. Meaning that in the recent past, we had the FCR, fludarabine, cyclophosphamide and rituximab for the young, fit patients; we had chlorambucil-based treatment for the elderly, unfit; and we had bendamustine-based treatment for those in between. So, all that are still fit. This is not anymore the case, because now thanks to the studies and thanks to the genetic certification based on p53 abnormalities and immunoglobulin gene status, now we can really stratify the patient based on this feature, plus the fitness of the patient, the age of the patient, but also for example, the comorbidities and the possibility to tolerate the new treatment.
So, all this together makes it that we don’t have any more standard, and we are looking for new standards, which will probably be very selective, very personalized based on this information that we will gather about each single patient.
We may say that nowadays we have a standard, which is the continuous BTKi treatment for patients with p53 aberration, because at the moment, it’s the one that has the longest follow up with the best, probably, efficacy in the long run. We might say that for the younger or for all patients with mutated immunoglobulin genes, we can really forget immuno-chemotherapy and use a fixed-duration like venetoclax plus obinutuzumab. But in-between, it’s really a decision of all patients where we know that the continuous treatment with BTKi for unmutated patient, for example, is very beneficial with the now seven years follow up, and not immediate PFS not yet reached.
But on the other side of this, the issue of the continued treatment versus a fixed-duration treatment which might be preferred by the patients. And now we know that we have indeed in this category of patients with venetoclax plus obinutuzumab, we have a median PFS that has been reached, but it’s close to five years.
So, I think that it’s a very dynamic field. We don’t have standards. We are looking for standards, but any standard will be somehow overruled, overcome by a new standard that we come up, and that thanks to the research that is continually improving the management of our patients.
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