Intriguing CLL Data From 2021 Conferences

EP: 1.Major Breakthroughs in Treating Chronic Lymphocytic Leukemia

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EP: 2.Intriguing CLL Data From 2021 Conferences

EP: 3.Noncovalent BTK Inhibitors for Chronic Lymphocytic Leukemia

EP: 4.Approved BTK Inhibitors for Chronic Lymphocytic Leukemia

EP: 5.BTK Inhibitors in the Presence of 17p Deletions or TP53 Mutation in CLL

EP: 6.Combination Therapies for Chronic Lymphocytic Leukemia

EP: 7.Adverse Effects of Concern When Treating Chronic Lymphocytic Leukemia

EP: 8.Novel Mechanisms of Action in Chronic Lymphocytic Leukemia

EP: 9.Ongoing Trials of Combination Therapy for Treating CLL

EP: 10.Importance of Clinical Trial Enrollment for CLL

EP: 11.Looking Toward the New Trends in CLL

EP: 12.Potential Approvals of CLL Combination Therapies in 2022

Susan M. O’Brien, MD: We [saw] some long-term follow-up from some important trials this year [during] spring meetings. One of them was the long-term follow-up of RESONATE-2 [NCT01722487], which was the trial that compared ibrutinib [Imbruvica] to chlorambucil for frontline use in CLL [chronic lymphocytic leukemia]. That trial now has a 7-year follow-up [period] and quite amazingly, ibrutinib did not [reach] a median progression-free survival [PFS] yet, meaning that the median has still not been reached. At 6.5 years, the PFS [rate] was about 61%. This is impressive given the fact that with ibrutinib, or really any of the BTK [Bruton tyrosine kinase inhibitors] inhibitors, we’re not generally talking about a high CR [complete response] rate, we’re not talking about high rates of MRD [minimal residual disease] undetectability, and yet we have these incredibly durable remissions as long as we do continue the therapy.

We got 4-year follow-up on the acalabrutinib [Calquence] frontline trial [ELEVATE-TN; NCT02475681] that led to the approval of acalabrutinib as a frontline therapy. That was a 3-arm trial of chlorambucil- obinutuzumab [Gazyva] versus acalabrutinib alone versus acalabrutinib-obinutuzumab. In that arm, the obinutuzumab was front loaded and stopped after 6 cycles, and then acalabrutinib continued indefinitely just as we do with all the BTK inhibitors. We already knew from the 2-year follow-up, not surprisingly, acalabrutinib either alone or with antibody was better than chlorambucil-obinutuzumab, but what was interesting [at] about the 4-year follow-up was that the 2 acalabrutinib arms appeared to be splitting quite a bit. When we look back at the 2-year data, they were slightly split, but pretty much the same. Now we see a big difference in favor of using the antibody with acalabrutinib. I personally have never used an antibody with acalabrutinib, but that data might make me reconsider.

Then another very important trial was the GLOW trial [NCT03462719] in terms of the potential registration of ibrutinib and venetoclax [Venclexta]. Another trial that we got 4-year follow-up on was the trial that led to venetoclax’s approval as frontline therapy. That was venetoclax plus obinutuzumab, where the obinutuzumab was given for 6 months and venetoclax was stopped after 12 months and compared with chlorambucil and obinutuzumab, one of the differences here being that this is a finite therapy trial as opposed to the ones with the BTK inhibitors. What we saw is data at 4 years [indicating] there was no median progression-free survival, but the PFS [rate] was about 87%. Keep in mind that that’s 3 years off therapy. Really nice, durable remissions with the possibility of stopping therapy.