Revolution of Therapy in Acute Lymphoblastic Leukemia - Episode 3
Transcript: Anthony S. Stein, MD: So for an older patient over the age of 50 or 60, it’s been shown that these patients don’t tolerate the intensive chemotherapy, especially the full dose asparaginase. And it’s recommended, at least during the induction phase of treatment, to use vincristine and prednisone. If the patient gets a remission you may during consolidation use a lower dose of asparaginase, like 1000 units, instead of the standard dose of treatment. And then it’s better tolerated during consolidation and later during the induction phase. But obviously for the patient over the age of 60, our 5-year results are still very dismal, and we’ll discuss later what newer agents can be used to try to improve the outcome for these patients.
Bijal D. Shah, MD: Absolutely. I think one of the things that we’ve observed anecdotally, and I think it’s also been seen by other series, is an enrichment for patients with p53 mutations, as they get older. I wonder if that might be informing some of the poor outcomes we see in the elderly patient population beyond the simple question of comorbid conditions, or less functional reserve as we approach them with these intensive chemotherapeutic protocols.
Mark R. Litzow, MD: Bijal, at the beginning you mentioned the fit and the unfit patient. What criteria do you use to distinguish those? It’s a challenging area.
Bijal D. Shah, MD: It’s extraordinarily challenging. It’s like asking someone who’s never had alcohol to describe what it is to be drunk, or to convincingly describe that sensation without having experienced it.
I will say that there are some very easy clinical presentations when a patient comes in age 65 in a wheelchair, with their oxygen tank for their severe COPD [chronic obstructive pulmonary disease]. That becomes a very easy determination. What’s much harder for me is the 72-year-old who has a history of hypertension walking into my office with very little prior medical therapy. And I’m trying to decide, what is this person’s functional reserve? And we have experiences where we’ve approached them intensively. Again, pediatric inspired regimens in some cases. We tend to use the Dana-Farber [Cancer Institute] protocol that was developed. Or even hyper-CVAD [cyclophosphamide/vincristine/doxorubicin/dexamethasone], and they do well.
We have the exact opposite scenario. I recall vividly a gentleman. He lifted weights, he was in the military as a younger man, very fit. After 2 cycles of hyper-CVAD in his case, he wasn’t fit any more. And we could no longer proceed with that treatment approach. While it’s not an easy determination, it’s one that I also spend a lot of time talking to the patients about, one-on-one, explaining to them, particularly if I’m in a conundrum like this, a 72-year old with minimal medical comorbidities, describing what we’ve seen, and working with them to develop a treatment protocol that is going to be something we can use. The last thing I want to do is interrupt therapy because I think that comes with more in the way of harm than anything else.
Jae Park, MD: I think the fitness of the therapy also depends on the therapeutic options you have for the particular groups. So…somebody walking in, older, or in a wheelchair with an oxygen tank, no matter what the therapeutic options are, is probably not going to do very well with the therapy. But the fitness determination for the intense therapy, considering factors or if they had a less intensive effective therapy, then all of a sudden then in the 75-year-old, the 80-year-old we may be able to deliver a good therapy and then achieve a good outcome.
So I think as the therapy changes, which makes it even more difficult when you’re assessing it, but it has to be; there’s no objective measure but at the same time it has to be somewhat individualized in determining what therapeutic options do I have. And of those, what this patient’s going to actually be able to receive. And I think the finishing of a therapy is very important because it’s one thing to get into the response, which is a first step. But as you said, they have to finish the therapy for the goal is to cure, otherwise it will be palliation. Then you may have to make those tough decisions, what is the end goal, and what are able to deliver to the patients.
Bijal D. Shah, MD: I absolutely agree. To put it in perspective, we put 70-year-olds on CAR [chimeric antigen receptor] T therapy for ALL, and with great success, meaning with little in the way of complications.
Jae Park, MD: Exactly. I think it all depends, and then also the degree of [adverse] effects [that] you expect, too, and not everybody with a CAR T may get CRS [cytokine release syndrome]. And there are some patients that you may anticipate get a lower degree, and then we treat an 80-year-old person with a lymphoma with a CAR T, and then, because we go through all these calculations or estimations that the likelihood is this patient is going to get severe CRS, going to the ICU [intensive care unit]. It’s so low that you can actually justify using the effective therapy in this setting. So I absolutely agree that it depends on the specific therapy and anticipated [adverse] effects.
Mark R. Litzow, MD: I often think that fit and unfit are not fixed definitions. You just mentioned you can have a fit patient and turn them into an unfit patient. You can have a patient that’s unfit because of their disease presentation, and you can treat them, and if you’re successful and get them into remission, they become a fit patient, and that can change your subsequent approach. So you can’t necessarily say, OK, this patient’s getting low intensity therapy from here on. You’ve got to be flexible and take that into account depending on how they respond.
Bijal D. Shah, MD: Yes, we actually call them modified DFCI [Dana-Farber Cancer Institute] induction, because we almost never follow the protocol, by doing exactly what you said. Maybe starting off with a lower intensity approach with the induction, maybe more vincristine steroid-based. But if they do well and they tolerate it well, stepping up with the addition of pegylated asparaginase, as we move into the consolidation phase.
Anthony S. Stein, MD: We’ve also found that by capping the asparaginase dose and not going more than, I think it’s 3000 and two-fifths of asparaginase you can actually decrease the liver toxicity, pancreatitis, and also be wary that if you have a patient with diabetes, you may also want to do an ultrasound of the liver, their fatty changes. You may also want to adjust your asparaginase dose. And also for some other reason, Hispanic patients are also more sensitive to the asparaginase treatment as well.
Transcript Edited for Clarity