ONCAlert | Upfront Therapy for mRCC

Case 1: Ibrutinib in CLL

Targeted Oncology
Published Online:1:00 PM, Tue January 28, 2020


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Anthony Mato, MD, MSCE: Last question for this particular case. Anybody want to tackle just defining if we’re considering chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab [FCR], what’s the genetic profile, the molecular profile that that patient should have? Just so we’re clear, if someone is going to get FCR, what are we, what’s ideal?

Sameer A. Parikh, MBBS: It would be a young patient, typically less than 65 years of age, who has mutated IGVH genes, and a low risk fluorescence in situ hybridization FISH]  profile such as deletion 13q or trisomy 12 or a negative FISH, and an absence of a TP53 mutation on a next-generation sequencing study.  

Shuo Ma, MD, PhD: So based on the ECOG study, even the immunochemotherapy for that particular group of patients is not inferior to ibrutinib, but it’s also not superior. The progression-free survival were no different. I guess for those group of patients you could consider either-or. For the rest of the patients, ibrutinib has outperformed immuno chemotherapy combination. Right? So, but that’s a definition.

I also want to bring back this patient’s particular profile and mention something that’s interesting.  Remember this patient has an IGVH unmutated status, and it has 11q deletion. We know that from conventional immunochemotherapy studies, a patient with IGVH unmutated status tends to have a worse treatment outcome compared to those with mutated patients.

When patients were treated with ibrutinib, the subgroup analysis from the RESONATE-2 study, which I mentioned first, that’s the ibrutinib single agent versus chlorambucil. If you just look at a patient who were treated with ibrutinib and look at a subgroup analysis of those patients who had mutated versus unmutated IGVH, there’s actually virtually no difference in their progression-free survival. It looks like the ibrutinib has been able to negate the negative effect of the IGVH unmutated status.

For 11q deletion patients, even more interesting. For patients who were treated with ibrutinib, we know that 11q deletion patients when they’re treated with chlorambucil they tend to do worse compared to those patients who don’t have 11q deletion. That is the opposite when they were treated with ibrutinib. So those patients with 11q deletion seemed to have a better progression-free survival compared with those patients who had, who does not have the 11q deletion when they’re treated with ibrutinib. So those adverse prognostic factors may not no longer be adverse when the patient were treated with ibrutinib-based therapy.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Anthony Mato, MD, MSCE: Last question for this particular case. Anybody want to tackle just defining if we’re considering chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab [FCR], what’s the genetic profile, the molecular profile that that patient should have? Just so we’re clear, if someone is going to get FCR, what are we, what’s ideal?

Sameer A. Parikh, MBBS: It would be a young patient, typically less than 65 years of age, who has mutated IGVH genes, and a low risk fluorescence in situ hybridization FISH]  profile such as deletion 13q or trisomy 12 or a negative FISH, and an absence of a TP53 mutation on a next-generation sequencing study.  

Shuo Ma, MD, PhD: So based on the ECOG study, even the immunochemotherapy for that particular group of patients is not inferior to ibrutinib, but it’s also not superior. The progression-free survival were no different. I guess for those group of patients you could consider either-or. For the rest of the patients, ibrutinib has outperformed immuno chemotherapy combination. Right? So, but that’s a definition.

I also want to bring back this patient’s particular profile and mention something that’s interesting.  Remember this patient has an IGVH unmutated status, and it has 11q deletion. We know that from conventional immunochemotherapy studies, a patient with IGVH unmutated status tends to have a worse treatment outcome compared to those with mutated patients.

When patients were treated with ibrutinib, the subgroup analysis from the RESONATE-2 study, which I mentioned first, that’s the ibrutinib single agent versus chlorambucil. If you just look at a patient who were treated with ibrutinib and look at a subgroup analysis of those patients who had mutated versus unmutated IGVH, there’s actually virtually no difference in their progression-free survival. It looks like the ibrutinib has been able to negate the negative effect of the IGVH unmutated status.

For 11q deletion patients, even more interesting. For patients who were treated with ibrutinib, we know that 11q deletion patients when they’re treated with chlorambucil they tend to do worse compared to those patients who don’t have 11q deletion. That is the opposite when they were treated with ibrutinib. So those patients with 11q deletion seemed to have a better progression-free survival compared with those patients who had, who does not have the 11q deletion when they’re treated with ibrutinib. So those adverse prognostic factors may not no longer be adverse when the patient were treated with ibrutinib-based therapy.

Transcript edited for clarity.
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