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iwCLL 2021 | The optimum approach to frontline treatment of CLL in 2021

Barbara Eichhorst, MD, of the University Hospital Cologne, Cologne, Germany, outlines the current optimum approach for the treatment of patients with chronic lymphocytic leukemia (CLL), and discusses how this may evolve in the future. In particular, Dr Eichhorst focuses on the use of targeted therapies such as Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors like venetoclax, and their use in combination. Dr Eichhorst talks on the advantages and disadvantages of the combinations, highlighting the use of BTK inhibitors with continuous administration or fixed-duration of BCL-2 inhibitors. Finally, Dr Eichhorst comments on the Phase III CLL17 trial (NCT04608318), which is comparing ibrutinib monotherapy to fixed-duration venetoclax plus obinutuzumab or fixed-duration ibrutinib plus venetoclax in patients with previously untreated CLL. This interview took place at the 19th International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Biennial Meeting, held virtually in 2021.

Transcript (edited for clarity)

In 2021 in CLL in many countries where the targeted drugs as BTK inhibitors, as well as BCL-2 inhibitors are approved and also reimbursed, we have for patients, particularly with high-risk features, including patients with TP53 mutation operation, as well as patients with unmutated IgHV status, the choice between continuous duration treatment with the BTK inhibitor versus time limited treatment with the BCL-2 inhibitor in combination with the CD20 antibody...

In 2021 in CLL in many countries where the targeted drugs as BTK inhibitors, as well as BCL-2 inhibitors are approved and also reimbursed, we have for patients, particularly with high-risk features, including patients with TP53 mutation operation, as well as patients with unmutated IgHV status, the choice between continuous duration treatment with the BTK inhibitor versus time limited treatment with the BCL-2 inhibitor in combination with the CD20 antibody.

There are different pros and cons for each of these therapies. And I think that’s the task right now for every physician to discuss with the patient, which of those two treatment options is the optimal one. Depending not only on the risk factors where we see maybe some disadvantage with respect to shorter time to relapse with time limited treatment, but having the option of free treatment there, on the other hand. And on the other hand, also the choice between continuous treatment, therefore commutative side effects on the one hand side, with continuous BTK inhibitors on the other side for these substances.

The very good handling with only few physician contacts while we have the ramp up period with the BCL-2 inhibitors and at the beginning of there for many contacts with the physician. And therefore also more frequent visits at the hospital. So, this might play particularly a role in patients who have not so easy access to the next hematologists or to the next center.

With respect to other criteria which of these treatments really were more efficacious and which was the best one, we did have to admit, we don’t know yet. And particularly now with the upcoming double combination of BTK inhibitors plus venetoclax giving us time limited therapy. The question is also here open: once this combination is approved is this better than continuous treatment with BTK inhibitor or BCL-2 inhibitor plus CD20 antibody? This discussion will be addressed in the CLL17 trial by the German Study Group. But I think we will need a couple of years until we have the answers on this trial, as well as maybe from other trials as from the UK group.

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Disclosures

Barbara Eichhorst, MD, has participated in consultancy and/or advisory boards with Janssen, Roche, Novartis, AbbVie, Gilead, Celgene, ArQule, AstraZeneca, Oxford Biomedica (UK), MSD and Miltenyi; has received speaker’s bureau from Janssen, Gilead, Roche, AbbVie, Novartis, Celgene, AstraZeneca, Adaptive Biotechnologies and Hexal; has received research funding from Janssen, Gilead, Roche, AbbVie, BeiGene and Astra Zeneca; and ha received travel, accommodation and/or expenses from Janssen, Roche, Novartis, AbbVie, Gilead and Celgene.

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