After sharing key takeaways on the management of BPDCN, expert hematologist-oncologists highlight unmet needs and forecast evolutions in care.
Bhumika Patel, MD: Dr Leblanc, what are some key takeaway points? What would you tell our audience about this because we’re going to be working together to make sure we take care of our patients from the community to the academic centers? What key takeaway analyses would you give physicians and our health care workers?
Thomas Leblanc, MD: I think as our discussion highlights here today, some of the most important things this paper tells us are that first, tagraxofusp has a very high overall response rate, about 75% or so, and that the complete response rate is also quite high, a bit over 50% generally, in first-line treatment. And so, this is the new standard-of-care first-line therapy for overwhelmingly most patients with blastic plasmacytoid dendritic cell neoplasm [BPDCN]. Also, the tolerability profile of this therapy is quite good, as we were more recently discussing. The challenge is you have to know about the nuances of capillary leak syndrome, what that looks like, how to address it, and to follow what’s in those NCCN [National Comprehensive Cancer Network] guidelines about good supportive care if you’re going to safely give this therapy. Otherwise, even with this highly effective therapy, it still should be viewed for most patients as a bridging therapy to a curative-intent allogeneic stem cell transplant, which really is the only chance for most patients with this disease to have a durable remission, a chance at a cure and long-term survival.
Dr Patel, as you think about this therapy and this rare disease, and managing it in the community setting, what are some of the clinical pearls you would offer up to community colleagues who are thinking about using tagraxofusp?
Bhumika Patel, MD: No. 1, I would make sure they’re getting a good history and physical on these patients, appropriate biopsies if the concern is a primary skin involvement, along with bone marrow biopsy imaging as needed. But when in doubt, if you see as you were saying, a rash that’s purplish-looking, that looks atypical, you see nodules, and you’re concerned about it, get a good biopsy. Make sure you’re talking to your academic colleagues like Dr Leblanc and saying; “Hey, I’m going to send a patient over to your guys. I just want to make sure,” if I’m concerned before initiating therapy. Then if I’m able to give the therapy tagraxofusp at my center, I would work with Dr Leblanc closely to make sure I’m following not only the NCCN guidelines but also working closely to make sure that once the diagnosis is confirmed, treatment is going as planned. I’m making sure these patients are admitted, approved for therapy, and watching for adverse effects. And if there are any concerns or questions, I would discuss them with my academic colleagues, pathologists, and dermatologists to make sure these patients are getting good care, as we’re moving along. I would say those are my takeaways.
I previously worked at an academic center, and I would say, coming to Greenville, South Carolina, I’ve been able to blend both of the worlds together, the academic side and the community side, where I would say a diagnosis is crucial prior to initiation of therapy. So a diagnosis and making sure that when in doubt, ask for help. There’s no harm in that, in making sure. There are a lot of colleagues who are willing to give you help and make sure you’re taking great care of these patients and even referring them over to them. But most people are open to discussing these cases, so I think that would be a big takeaway. And if the patient is fit, use tagraxofusp up front, and start working on their transplant eligibility up front, so you can get their tissue typing and can make sure that once they’re in CR1 [first complete response], you take these patients to transplant if they’re a candidate for it. I would say those are the key takeaways from all of my community colleagues and academic colleagues I work with.
Thomas Leblanc, MD: And remembering that CNS [central nervous system] disease is pretty common here, so let’s also underscore that patients getting this therapy need to have regular lumbar punctures. And even if there’s no disease there, which there often won’t be at the beginning, they need prophylactic intrathecal [IT] chemotherapy, just like we would do with acute lymphoblastic leukemia [ALL] kinds of treatment.
Bhumika Patel, MD: Right, because we don’t know yet if tagraxofusp crosses the blood-brain barrier. So to Dr Leblanc’s point, make sure that’s incorporated, IT chemotherapy, with all your patients because the highest chance of relapse is in the CNS, so we want to stay ahead of the game for these patients.
Thomas Leblanc, MD: One other thing I wanted to mention that I forgot to bring up earlier is, there’s a pretty decent incidence of other hematologic malignancies in patients who have BPDCN. I have some of these patients in my practice who present with skin lesions. You do the biopsy, you find BPDCN. And then to stage them, you do a bone marrow evaluation, and you’re looking for BPDCN there. You maybe don’t find it, but you find something else like primary myelofibrosis, or CMML [chronic myelomonocytic leukemia], or maybe something that looks more like MDS [myelodysplastic syndrome], or some other myeloid malignancy. It’s not entirely understood why, but that is something that happens with this disease, and that complicates how to treat these folks as well. Those would be cases where you really want to partner with somebody at an academic center who can help you figure out what the right treatment plan may be, because there are so few data about these unusual situations. But that happens more commonly with this disease interestingly, for reasons we don’t understand.
Bhumika Patel, MD: Just to add to that, outside of the NCCN, there are North American consensus guidelines that have just been released by [Naveen] Pemmaraju, [MD,] and colleagues in Blood. I think it’s a great resource for community physicians, academic physicians to use on how you should be evaluating these patients. And to Dr Leblanc’s point, [make the] diagnosis up front, making sure there are no coexisting myeloid neoplasms with BPDCN, because there are categories of AML [acute myeloid leukemia] that have plasmacytoid features too, which is different from BPDCN. You want to make sure you get a good diagnosis, and make sure you get that upfront IT chemotherapy. Clinical trials are another aspect to look at too because if you do have an option of clinical trials, in the upfront setting or in the relapsed/refractory setting, you want to consider those as you work with your academic colleagues.
Thomas Leblanc, MD: To wrap things up, let’s underscore that there unfortunately are many unmet needs still in the BPDCN space. Although tagraxofusp is a really exciting new advance and the new standard first-line therapy that gets more people to be bridged to transplant as we talked about, it doesn’t work forever. It doesn’t work for everyone. It doesn’t work as well in patients who are more heavily pretreated with relapsed or refractory disease, and it’s not a curative therapy. So the big unmet need is that we need more treatments that will work in people who’ve already had tagraxofusp, more treatments that will work without a lot of toxicity, the way we see horrible toxicity with the acute leukemia kinds of therapies, without as much efficacy as we would want. And ideally, we need therapies that can get rid of this disease without forcing us to send people to an allogeneic stem cell transplant, which has a high morbidity and mortality rate associated with it even at the best of centers.
Bhumika Patel, MD: I agree with Dr Leblanc. We are going to have to keep investigating BPDCN and look at alternative agents. I think that’s where clinical trials are going to be imperative. MRD [minimal residual disease] evaluation has not been established in BPDCN yet as it has been in ALL, so I think there is more to come. We’ll have to look at MRD testing, and see in patients who are not able to go to transplant, if they’re MRD-negative, how long can they remain on therapy, and how do we evaluate that? I think there is a lot more to come from all the excellent academic centers where there are BPDCN centers of excellence. The data are going to be exciting to see what’s to come, and there are a lot of trials with Dr Pemmaraju’s group and Dana-Farber [Cancer Institute] that are going to help us better address the unmet needs of these patients.
Thomas Leblanc, MD: Thanks so much for having this discussion with us, Dr Patel. I learned a lot, and I enjoyed talking with you. And thanks, everyone, for listening in. I hope this is helpful for your practice.
Transcript edited for clarity.