DR LOVE: Where you are today about first-line therapy of CLL in the older and younger patient? I know it’s like a huge question, but I’m just — I ask a lot of people about that, and interesting how there’s a diversity of thought about it. How do you approach these patients?

DR SEHN: Yes. So in Canada, where I am, obviously things rely a little bit on funding. I think CLL is an entity which is in huge flux right now. And I think we are going to see a lot of changes in the management algorithm, where people probably try to trend away from the high-intensity, highly toxic up-front therapy. And these novel targeted agents undoubtedly are going to be making their way more typically into the front-line setting.

Right now, though, I think, for the average patient who presents with CLL who is still a candidate for purine analogs, I think a purine analog-based therapy is still probably the front-line choice for most patients, so FCR or, in my own clinic, we typically use FR as a front-line therapy.

One of the combinations that’s kind of challenging, that is the bendamustine and rituximab, which we know has been compared head to head against FCR and showed to be very effective, probably not as intense and as effective as FCR, but a much more tolerable regimen. And so I think in many patients, up-front bendamustine and rituximab is a very reasonable up-front standard of care.

Aside from that standard purine analog or bendamustine and rituximab chemotherapy, I think what we’re starting to get excited about are the novel agents like ibrutinib, so much lower toxicity level and certainly now become a mainstay of therapy in the relapsed setting, thinking about using a drug like ibrutinib up front in a more elderly patient where maybe you want to avoid chemotherapy.

In my own clinic, we have funding for ibrutinib up front for patients with 17p deletion, where we know that chemotherapy is not very effective and ibrutinib has now, I would say, become the standard of care up front for patients with 17p deletion. It’s much harder for us to access right now for elderly patients, but for an elderly patient who is not a candidate for chemotherapy and rituximab, I do think about using chlorambucil and obinutuzumab, which again has been shown to be a very effective combination for patients who are elderly and who you don’t want to treat with a more toxic regimen.

DR LOVE: One of the things I’ve heard from investigators, particularly in the younger patients, is the issue of short-term chemo for a long-term, nonmaintained remission, as opposed to having to take a drug — ie, ibrutinib — every day by mouth. Is that your thinking? Are you thinking that you’re curing people? Are you concerned — I’ve heard people express general concerns about people — in addition to the economic issues — I don't know — tolerability, toxicity issues with long-term ibrutinib. How do you really weigh that out right now, putting aside the reimbursement issues?

DR SEHN: It’s a real challenge. So we’re excited to have all these novel compounds available, but many of the novel targeted compounds are, as you mentioned, drugs that are meant to be taken for the long haul. So these are drugs that patients take until they have evidence of progression or some element of intolerability.

What we’re really looking forward to are the series of clinical trials that are underway that are going to be comparing, head to head in the up-front setting, ibrutinib against standard immunochemotherapy, because there are going to be tradeoffs in terms of toxicity, duration of therapy, cost, where I think we need to fully understand the risk-benefit ratio of all of those factors.

Right now, without comparative trials, I think you need to have this discussion with each patient and present to them the treatment options. And they need to be part of the decision-making process. Not too long ago, I sat down with a patient just like this, where the decision was, should the patient get treatment with fludarabine/rituximab, or should we consider ibrutinib? And this is a patient where funding was not an issue and it really came down to balancing the difference between the toxicities between the 2 regimens.

But what played on this patient’s mind the most is, he didn’t want to be on a drug indefinitely. He thought the idea of getting 6 months of treatment and being done with it was a very attractive concept. So without clinical trial data telling us that he’s going to do better in the long run from a drug like ibrutinib up front, he made the choice to go on the shorter course of chemotherapy and rituximab, knowing that he can always get ibrutinib in the second line if he needed it. And I think that was a very rational decision on his part.

But I think there are going to be choices to be made. And what we really need is data to point us in the right direction in terms of what’s going to be most beneficial for the patient. But until we have those comparative trials, I think it’s a matter of weighing in that risk-benefit ratio for each patient and bringing in their personal preferences. So what do the patients want? What’s their lifestyle? What is going to impact their lifestyle the most?

None of these drugs, unfortunately, come without toxicity. So even a drug like ibrutinib, which we feel to be generally well tolerated by most patients, still requires patients to take a daily pill. They can still have symptoms related to the drug, either GI symptoms or easy bruising, rashes, the risk of bleeding, the risk of atrial fibrillation. Nothing is without long-term risk.

And the other thing is, although now we’re starting to see data — I mean, some patients have been treated for beyond 5 years with ibrutinib, maybe getting close to 10 years now in the earlier trial patients. We still don’t have very, very long-term toxicity data on ibrutinib. And I think there’s a little bit of that unknown still related to these agents. What is the long-term cumulative toxicity of these drugs?

DR LOVE: This concept of short-term treatment and then long unmaintained remission, in your mind, does that also apply to, say, bendamustine/rituximab and obinutuzumab/chlorambucil? Same kind of thinking?

DR SEHN: I think it’s the same kind of thinking. So in all of these lymphomas where we don’t have an immediate cure, you’re going to be managing this patient over the course of their lifetime. And you’re not just interested in what’s the best thing you can do for this patient now, but what’s the best thing you can do for this patient for the rest of their lives, knowing that this treatment, it’s a marathon. It’s not a sprint.

We’re trying to keep this patient alive as long as possible, living well without knowing that they even have lymphoma in the best-case scenario — minimizing the toxicities associated with their treatment. And I think the issue of sequencing and competing toxicities, as we get more treatment options, those become much more relevant in our decision-making process.

Non-Hodgkin lymphoma (NHL), Hodgkin lymphoma and chronic lymphocytic leukemia (CLL)

Acute and chronic leukemias and myeloproliferative neoplasms

Multiple myeloma (MM)