Managing MRD-Positive Acute Lymphoblastic Leukemia

Richard M. Stone, MD: MRD [minimal residual disease]—we all measure it, but what do we do with it? We’ll start with Jae this time. We have a young adult with ALL [acute lymphoblastic leukemia]who is given the 10403, and their MRD by flow was 0.04% or a point even higher after the initial therapy. Do you say, “Oh my God, I’ve got to do something different”?

Jae Park, MD: If they’re MRD positive at the end of induction 1, 2, or 3 months or closer to that mark, or they have hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone], if they have detectable MRD—whether it’s 0.01% or closer around that—I do switch therapy. Because the data are clear: The continuation of the chemotherapy is unlikely to benefit.

Richard M. Stone, MD: Would you wait 3 cycles?

Jae Park, MD: I rarely switch therapy after 1 month. Perhaps with the CALGB induction 1—that’s how the trial was designed there—and our pediatric-inspired regimen we were using for 40- to 60 year-olds. We didn’t make the treatment decisions that would change until induction 2, which roughly falls on the 3-month mark; not after induction 1, but induction 2. I use the 3 months to complete and switch therapy to, in this case, blinatumomab for B-ALL [B-cell ALL] MRD positivity. I do switch therapy at that time and in conjunction with those we’re still working up the donor for a potential consolidative bone marrow transplant, especially for younger patients when they become MRD negative.

Richard M. Stone, MD: What will you tell them at 3 months MRD positive but otherwise OK?

Jae Park, MD: I would tell them that your disease is acting with the high-risk features with MRD positivity, with first chemotherapy refractoriness; the continuous chemotherapy is not going to reach the MRD negativity. The goal is to cure; we first have to cure MRD negativity. The best way to get there is blinatumomab in this setting. It’s unclear at this time whether blinatumomab continuation could be curative vs allogeneic bone marrow transplant.

Richard M. Stone, MD: Bijal, what would you do for a patient who’s MRD positive after getting chemotherapy?

Bijal Shah, MD: BLIN [blinatumomab] and transplant.

Richard M. Stone, MD: You tell them right then and there. How many seconds on blinatumomab [BLIN] do you give, Ryan?

Ryan D. Cassaday, MD: It usually ends up being 2 for practical purposes. I’m not sure more than 1 is necessary, particularly for patients who are going on to a stem cell transplant. From a practical perspective—whether it’s identifying the donor or confirming response, even though around 80% of patients will be MRD negative after 1 cycle based on the BLAST trial—our transplant program wants to confirm that they’re MRD negative before they kick into gear in terms of confirming the donor. The time that it takes to do that, I’m usually starting the second cycle of blinatumomab. They might finish that completely or get a couple of weeks into it before the conditioning starts.

Richard M. Stone, MD: Bijal, what do you do about chemoprophylaxis in people who are going to have fairly early transplants?

Bijal Shah, MD: The prophylaxis doesn’t stop. We’re giving 1 to 2 doses of intrathecal per cycle depending on where they are.

Richard M. Stone, MD:Let’s say they get a couple of cycles of hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]. They’ve probably gotten 4 doses of intrathecal. This hypothetical patient is going to need blinatumomab. Do you continue? How many total doses do you give before you do the transplant?

Bijal Shah, MD:I’ll give 1 per cycle. If they’ve already finished 2 cycles and their CNS [central nervous system] is negative on those 4 initial doses of intrathecal, we’ll go for 1 intrathecal with each subsequent one.

Richard M. Stone, MD: So you’ll have a total of about 6 before the transplant?

Bijal Shah, MD:That’s correct.

Richard M. Stone, MD: Jae, how do you view that?

Jae Park, MD: I do the same thing. Usually right before BLIN starts and right after BLIN finishes, there usually are about 2 cycles.

Transcript Edited for Clarity