Managing MRD-Negative Acute Lymphoblastic Leukemia

Richard M. Stone, MD: Let’s talk about MRD [minimal residual disease]-negative patients and if there any MRD-negative patients that you would think of transplanting in first remission.

Jae Park, MD: The one group of patients is those with KMT2A or an MLL 0-range ALL [acute lymphoblastic leukemia]. Even if they become MRD-negative we worry, so I’d send them to transplant. Hypodiploid [ALL] is the other [group of patients] that I do [a transplant]. TP53 and the Ph [Philadelphia chromosome]-like [patients] are the ones I’m struggling with. But with TP53, there is data from [The University of Texas] MD Anderson [Cancer Center] [that] hyper-CVAD [cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone] may not be as bad of a marker for frontline hyper-CVAD in the Ph-like [patients] when they become MRD negative. These are the 2 situations that I usually do send them to transplant, especially if they’re younger because the data is less clear and long-term follow-up is better with a transplant.

Richard M. Stone, MD: Let’s discuss T-cell patients and whether or not to send them to transplant.

Bijal Shah, MD: In general, I send the early T-cell patients to transplant and those who have persistent MRD.

Richard M. Stone, MD: When seeing a patient with B-cell ALL walk in the door, what are the factors that go into deciding whether to transplant?

Ryan D. Cassaday, MD: My usual approach is to not recommend a transplant in first remission unless they have some feature about their disease that has demonstrated to be high risk. With Ph-positive patients, typically I’m recommending a transplant in first remission. KMT2A rearranged patients I’m recommending transplant in first remission, and ETP early T-cell precursor also. Those 3 are the ones if a patient is eligible for transplant, are the ones that I’m sending, irrespective of how early or how deep a remission they’re in.

The others, it ends up being more than an MRD-based decision. The other high-risk groups, like the hypodiploid, which is not a common situation in adults, and high prevalence of TP53 mutations in that subgroup. While it’s hard to extrapolate this data, there were back-to-back studies published in the Journal of Clinical Oncology a couple of years ago that showed no clear benefit from those patients undergoing transplant in first remission. However, those were pediatric studies. The assumption that transplant is going to absolve all sins and work across subtypes is not true. There are biological subtypes where it isn’t effective and maybe that’s one of them. Beyond those handfuls of situations, those are the ones that I’m generally not recommending transplant unless they have persistent MRD.

Bijal Shah, MD: I would automatically transplant a Philadelphia chromosome-like ALL patient, even if they’re MRD-negative. The CRLF2s have a high propensity for relapse down the line. The big challenge is, what is MRD-negative? It’s with the sensitivity of the tools that we have in hand, we can get down to 1x10-4 with good flow, 1 x 10-6 with NGS [next-generation sequencing], but there are 6 logs below that that we’re not going to see. My experience has been that these CRLF2s, even when we get them MRD-negative, have a strong propensity for relapse.

We wish we could succeed in transplanting almost everybody, but there are a whole host of psychosocial reasons why they don’t make it to the transplant. We’re probably transplanting around 20% or 30% of the patients that we see. We will succeed in curing around 35% of adults with ALL, and hopefully, we can do better by incorporating multimodality therapy. I consider allogeneic transplant to be part of that.

Jae Park, MD: The Ph-like, not all patients, are going to get transplanted. The one thing is that pediatric regimen, I think the age groups with asparaginase-regimen the cure rate hopefully, at least the CALGB data shows a little bit higher. Depending on the frontline regimen that you may be using … response in terms of transplant. I certainly don’t transplant as many. The majority don’t get transplanted because luckily the majority are able to get MRD-negative with their front-line regimen—just over 50% or so depending on the regimen. So I think they would just count the MRD negativity rate and I think you end up being, well, it’s a minority but still by 30% to 40% of it belong to the high-risk category. Either because they are MRD-positive or because they are presenting with a KMT2A [mutation] or other high-risk. Those are the ones we are considering for transplant, and of those not everybody makes it. They first have to convert and we would like to get to MRD negativity before sending to transplant.

Richard M. Stone, MD: There is a risk of not being able to get a relapsed patient into another remission, to consign everybody to transplant in first remission is a big deal. It’s a disease of younger adults where some of the results with the pediatric-inspired therapy, both from Dana-Farber Cancer Institute and the CALGB [Cancer and Leukemia Group B] study. Most of those patients don’t get transplanted. I tend to reserve it for beyond first remission, but if you miss the boat, you may miss the boat forever. It’s also tough to see somebody succumb to a first remission allogeneic transplant or have major toxicities, which can occur.

Transcript Edited for Clarity