Approaches to Treatment of Ph- ALL

Ibrahim Aldoss, MD: Are your treatment goals different based on age and Ph-negative ALL [acute lymphoblastic leukemia]? And typically, if we're still talking about AYA (adolescent and young adult) versus older adults, or even with the AYA, there's always debate about what the upper age limit is for AYA pediatric regimens. For younger adults, we tend to give pediatric regimens because clearly there is a higher chance of cure with these regimens compared to adult regimens. One of the main barriers for pediatric regimens in older patients or AYA is asparaginase toxicity; clearly there's correlation between asparaginase toxicity and increased age. With other drugs like vincristine, frequently patients suffer from peripheral neuropathy when they are in their 40s and 50s compared with someone in their 20s or younger. There are some limits. What we usually do is try to offer this pediatric regimen up to age 50, sometimes even age 54. And to mitigate some of the adverse effect of asparaginase, we tend to reduce the dose of asparaginase rather than giving 2000 international units per meter squared (iU/m2, we try to reduce the dose to 1000 international units per meter squared as the pharmacokinetics data show actually this dose is adequate and inhibition as per gene can give you results for patients treated with these regimens. And it seems toxicity is better when you use a reduced dose. But as I say, the problem is that even with reducing the dose is the increase associated with more toxicity, so we see more interruption, more discontinuation of these regimens compared to younger patients. And even when patients receive similar pediatric regimens, we see the prognosis is not as good as someone who's younger than 18 years old. There is still a difference even by using these modern pediatric regimens in younger adults with ALL. Is that your approach too, James?

James K. McCloskey, MD: Yes. It's very similar. I agree that particularly when we consider the pediatric-inspired regimens, the asparaginase is, of all the agents, the one that often causes us a lot of issues and is more likely to cause unpredictable issues, so clotting and bleeding are always a concern. For us, our upper age limit for our pediatric-inspired regimen is really 40 years. That's where we draw the cutoff. We have pushed it up higher than that. And we often find even between the ages of 35 and 40, as you mentioned, we have a lot of difficulty maintaining treatment tensity. For all these patients, our goal is always to cure them if possible. And one big difference for us is that anyone in our center who achieved an MRD [minimal residual disease] negative remission by cycle 1 of consolidation with a pediatric-inspired regimen, we don't recommend transplant for those patients. That is a big bridge, whereas for patients who are older, we will often discuss and highly consider a transplant irrespective of their MRD status. That's certainly one difference as they proceed on through induction and consolidation.

Ibrahim Aldoss, MD: Yes. We have the same approach. When we see the patient is treated with less curative regimens and they're unable to tolerate the curative agents in the regimen, we tend to recommend transplant. Even if they achieve early MRD, we consider transplant, and it depends on various factors. But a newly evolving thing with older patients, since they don't handle chemotherapy well, is the introduction of these novel agents early like blinatumomab, inotuzumab, this may actually change the outcomes of these patients. But, again, the study's still early, and we have to have a longer follow-up to see if we can avoid transplant and the complications of the transplant if these drugs are introduced early in the regimen.

Transcript Edited for Clarity