DR BROWN: So this is a 65-year-old gentleman in excellent health with no significant medical problems who I had met probably 2 years prior to the time he came to need treatment. And we’d identified that he had unmutated higher-risk IgHV and trisomy 12. And he progressed steadily toward treatment and ultimately required it based on anemia, developing thrombocytopenia and lymphadenopathy.

DR LOVE: So Hagop, what would you be thinking about for this 65-year-old man?

DR KANTARJIAN: So today I divide the patients into 2 categories, the ones who are either FISH-positive for 17p, 11 or unmutated. And those we know that we cannot cure them with FCR therapy. And those in the future could be moved into the B-cell receptor inhibitor combinations. But if this patient had a mutated somatic hypermutation together with a negative FISH status for 17 and 11, I would probably have gone for FCR, because FCR is 3 days times 6, sometimes times 3, so a total of 9 or 18 days. And now we have 14-year follow-ups that show that about 60% of the patients are in a plateau phase. And this is about 30% to 40% of the patients. So this is what one might consider in this patient.

This guy is 65, unmutated. I would still consider FCR. Some people would go for bendamustine/rituximab. But I want to highlight the study at ASH, which compared FCR to BR and, even though there was no survival difference, there was a significant difference in the incidence of MRD negativity and in the disease-free survival. So a 65-year-old man, even though he’s unmutated, I would probably go with FCR up front.

DR LOVE: I want to get Jennifer’s thoughts about that presentation at ASH. But suppose he were 75?

DR KANTARJIAN: Seventy-five, I would probably look at the BCR receptor inhibitor, front-line therapy, something like ibrutinib with rituximab or others.

DR LOVE: Interesting. In general, Jennifer, how are you approaching a patient like this, and what about as they get older?

DR BROWN: Right. So outside a trial setting, I would favor FCR for the 65-year-old perfectly well patient. And again, that was supported by the CLL10 study that was reported at ASH that Hagop referred to. The study was mildly marred by the fact that the BR arm had a disproportionately greater number of patients over 65 as well as a higher rate of unmutated IgH patients, therefore making the arms not perfectly balanced. That being said, the fact that FCR doubled the likelihood of being negative for residual disease in the bone marrow and peripheral blood, I found it very impressive results compared to the results of BR. And this was reflected in it meeting its primary endpoint of a significantly greater progression-free survival.

DR LOVE: And again, as you go up in age, 75, 80, 85, how do you think it through?

DR BROWN: Right. So 75, I’m not considering FCR anymore. I would try to put the patient on a clinical trial of a B-cell receptor pathway inhibitor in all likelihood. In the absence of such trial, I would consider a bendamustine/rituximab regimen or an obinutuzumab/chlorambucil regimen. I don’t think we have data to address those 2 regimens comparatively.

DR LOVE: So can you talk about what happened with this patient?

DR BROWN: Right. So this patient I was viewing as an FCR candidate patient. And we had a clinical trial with FC with obinutuzumab. And so he was very interested in that trial and enrolled. And the initiation of the therapy involved a 100-mg dose on day 1, as is typical for obinutuzumab, and he did fine in clinic, had just the mild Grade 1-type infusion reaction, went home and developed a low-grade fever, chills. He said that literally he felt he could watch his lymph nodes shrink under his eyes over a couple of hours. And he felt okay, stayed home, didn’t even call that night.

Came back in the following morning. His white count, which had been 80,000, was 4, and he actually also had Grade 4 transaminitis, which was not something we were expecting, had not been reported with the drug. But since then, it has been reported in some context and was seen in this study. That mandated that he be removed from the study.

DR LOVE: What happened after that?

DR BROWN: So I gave him a little while to — he actually did develop some neutropenia from the 100 mg of obinutuzumab, maintained his response. And then about 4 weeks later after he had recovered from that, I treated him with FCR off study and he achieved an MRD-negative complete remission.

Chronic Lymphocytic Leukemia (CLL)

Chronic Myeloid Leukemia (CML)

Acute Myeloid Leukemia (AML) and Acute Promyelocytic Leukemia (APL)

Myelodysplastic Syndromes (MDS)

Acute Lymphocytic Leukemia (ALL)