Naveen Pemmaraju, MD

James, what are your closing thoughts? Looking at the features of future directions for BPDCN [blastic plasmacytoid dendritic cell neoplasm] and related fields, what are your thoughts as you look at all these data?

To summarize, it keeps coming back to communication: talking to your colleagues, talking together, working together. One thing I’m always struck by is that a lot of times I get calls from folks in the community who see older, frail patients and look at them as not having options. It seems overwhelming to treat 1 of these frail, older patients. That’s completely true. Just like in AML, a lot of these therapies are tolerable in older patients. These are aggressive hematologic malignancies. If we don’t address them, they lead to a rapid decline in quality of life and quickly result in the patient’s death. The more work we can do together, both in the community and at large academic centers, the sooner we’re going to bring better treatments into this disease space for folks with this rare disease.

Wow. I want to thank both of you for an illuminating discussion. I hope the audience feels the same way. On behalf of my friends and colleagues, Dr Alejandro Gru and Dr James McCloskey, I’m Dr Naveen Pemmaraju. I thank the 

® team for their help in getting us all together with my friends to discuss the state of BPDCN, but also some glimpses into our thoughts for future directions for clinical care and research. We hope today’s program was valuable for everyone, and that you acquired some practical knowledge that you can put into your clinical practice now and into the future. With that, thank you to the 

™ team. We’ll sign off for now. Be well. Thank you all very much.

Videos

Closing out their discussion on the management of blastic plasmacytoid dendritic cell neoplasm, expert panelists look toward the future treatment paradigm.   

BPDCN: Future Directions in Care

Let’s move into the final portion of our discussion, which is looking to the future. You both nicely summarized for us what’s going on in the pathology lab and in the clinic. I put together a few slides for our discussion. One of the most promising aspects of BPDCN [blastic plasmacytoid dendritic cell neoplasm] is building on the success of the CD123 fields with the tagraxofusp agent. What’s really exciting, which I’m helping to co-lead, is the IMGN632 program. It has a name now, pivekimab sunirine.

In the relapsed/refractory BPDCN setting, as we showed at ASH [American Society of Hematology Annual Meeting] a year or 2 ago, this next-generation CD123 antibody-drug conjugate is showing some nice safety and efficacy results early on in the relapsed/refractory setting. This is a sample of the first 29 patients treated, ages 72 with a median of up to 82 years. James mentioned the median age of the prior experiences, so it’s in line with that. The majority were men, as we’ve come to expect. You can see the skin, bone marrow, lymph node involvement, and prior therapies shown here. Almost half the patients had prior tagraxofusp.

With this novel antibody-drug conjugate, in this experience, we saw no capillary leak syndrome. That’s a notable thing compared with the prior experience. There were no drug-related discontinuations or deaths in these first 29 patients during the induction period. Among the common adverse events, they were fairly manageable with some thrombocytopenia, neutropenic fevers, and hyperglycemia—approximately 10% each. As you think about the new agent, it’s an IV [intravenous] drug given every 3 weeks, as 1 dose every 3 weeks, and it can be administered in the outpatient setting.

The efficacy results are shown here. This is a very heavily pretreated group of patients, but you do see a 29% to 30% overall response rate. This was granted the BTD, or breakthrough therapy designation, for the relapsed/refractory cohort. Based on these very promising results, the study is open enrolling in the frontline setting in United States and Europe, known as the CADENZA study. I’m the lead PI [principal investigator] for this, and this is active and enrolling in the United States and Europe, giving patients another option for their BPDCN therapy.

In addition, CAR [chimeric antigen receptor] T-cells [therapy] is starting to take over every field, with lymphoma leading the way, but many of our other fields are markedly far behind in terms of developing therapies. That’s suggested in laboratory and phase 1 testing only. There are CD123 CAR T cells being developed across the world. Usually, they involve both AML [acute myeloid leukemia] and BPDCN. Some are BPDCN specific, but the concept is targeting CD123. Can you get cell kill in the BPDCN without affecting the normal hematopoietic stem cell compartment? That’s the problem and issue with CD123 therapy.

Multiple groups are trying for combination therapies. Our group, Dana-Farber [Cancer Institute], and City of Hope have opened a doublet and now a triplet trial with CD123 if you can believe it. [The trial for the combination] tagraxofusp, venetoclax BCL2, and azacitidine, is open and enrolling in frontline and relapsed/refractory BPDCN. It’s usually centered on older patients and those unable to get cytotoxic chemotherapy, but you have to be able to get this triplet.

As James mentioned, with the occurrence of CNS [central nervous system] disease, we’re doing lumbar puncture [LP] in all our patients. It’s changed the way we look at BPDCN, think about it, and think about it at relapse. In the publication our group put out last year, I was surprised to see that we reported 22% CSF [cerebral spinal fluid] positive at some point during their BPDCN course. This is a retrospective analysis. The number is higher if you’re systematically looking for it. What we’ve done is adopt an ALL [acute lymphoblastic leukemia] Burkitt-type model for LP. In AML, only 3% to 5% of patients have CNS involvement. Here it’s much higher, so we need to be thinking about that and incorporating it into our therapies.

At The [University of Texas] MD Anderson [Cancer Center], a lot of our clinical trials for BPDCN are up and running. We’re trying to put all these concepts together and move toward a more total-therapy, triplet-therapy approach. Alejandro mentioned multiple myeloma and some of these other aggressive hematologic malignancies that have moved from a more acute emergent presentation to a more chronic disease over time. This is 1 clinical trial that’s trying to put everything together: hyper-CVAD [cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone], CD123, venetoclax, lumbar punctures, getting correlative testing, and maybe eliminating stem cell transplant in the future.

I have 1 last important concept to bring to our audience. As rare as BPDCN is, it often appears with another hematologic malignancy, most commonly MDS [myelodysplastic syndrome] and CMML [chronic myeolomonocytic leukemia], but I’ve seen cases of MPNs [myeloproliferative neoplasms] and T-cell ALL. While you’re distinguishing them, remember that you could have more than 1. You could have 2 diagnoses at the same time, so that may alter what you do.

The last concept is that we’re trying to distinguish BPDCN from AML. Our colleagues from [Memorial] Sloan Kettering [Cancer Center], led by Ross Levine and Wenbin Xiao, showed that there’s a small entity between BPDCN and AML. They termed it PDC [plasmacytoid dendritic cell]–AML. That’s quite compelling. Usually 3% to 5% of cases are associated with 

 mutation, which may lead to an upregulated PDC. They did have more skin lesions and worse overall survival, and CD123-targeted therapy may help. Alejandro, maybe you can comment on the elucidation of these in-between entities. Where do you think the field is going?

This is an excellent part. I had a case of this 2 weeks ago. I was talking to your colleague, and I said, “Let me email Naveen and tell him about it.” It’s a peculiar entity because the blasts have the same morphology. These cases have an interesting phenotype. They’re often CD123-positive, CD4-positive, with the same level of brightness and intensity you see in BPDCN. Interestingly, a lot of times they’re CD56-negative. In this case they lack CD56 expression. They have myeloblast markers like CD34. It’s not common to see in BPDCN, but it could happen. It’s not a diagnosis of exclusion.

The last thing is that there are very interesting data. I haven’t seen the numbers, but they were published in a paper in 

 2 years ago. It looks like these cases are TCF4 positive. As you know, because you were part of the paper, which looked at TCF4 expression across a spectrum of hematologic myeloid and lymphoid malignancies, it appeared from the study that all cases of AML were negative for TCF4. Perhaps this might be the sole exception. I love what you mentioned about how this might be an in-between entity because it has TCF4 expression. Our case was diffusely positive for TCF4, but it had an unusual phenotype. It had 

 mutation, and about 10% or 20% of these cases have either trisomy 12 or trisomy 13. That’s also an accompanying feature that you see. This is an entity in which we’re going to study more and separate from BPDCN if there is a true separation. The older literature mentioned that 

 mutations aren’t very common in BPDCN. 

 is a coexisting mutation in this entity, but 

 appears to be much less frequent. This is a unique and intriguing entity, and we need to learn more about it.

Shared insight on a number of novel therapies and treatment modalities being investigated in patients with blastic plasmacytoid dendritic cell neoplasm. 

Emerging Therapies in BPDCN 

I guess the question for us is this: we have a field and clinical trials going, but I still think the problem a lot of times is travel, cost—these kinds of barriers. You and I have spoken about this many times. You passionately care about this. I find you to be a great advocate for patients. James, do we need a national dedication to a rare disease like this? What’s the solution?

It’s a real challenge. In our institution [Hackensack University Medical Center]—we probably all feel this—we’re pushed to open trials we can accrue to, especially in the current environment, because we have limited staffing. As someone leading a division, it’s hard to say I’m going to open a trial with 2 people and that we’ll be happy about it if we’re participating with multiple other sites. First, the important thing is communication. The last person I had met with you in Texas. She went to Harvard [Medical School] and met the folks there. At the end of the day, everyone had a slightly different take. She ended up getting standard care with us. It was a lot for her because this is a challenging conversation. Inpatients can often feel overwhelmed. Not everyone can make it to Texas. In their 70s, a lot of patients don’t want to spend their time traveling. They want to be close to home.

The most important thing is communication. We’re lucky in this field because we have a lot of people who pick up the phone and answer emails. When there are questions, we’re all available to answer them. Sometimes that communication might connect that patient with a trial, or it might be thinking outside the box and talking about something that’s off-label but might fit better with that patient’s goals for their quality of life and their objectives in terms of their own personal care.

What you say flows nicely into this next question, which we’ll ask Dr Gru to lead us on. You’ve both emphasized this multidisciplinary approach, and I think we all hold the pathology team above dermatology and hematology. General pathology is the highest and most important member of this team. Without a diagnosis, you can’t start anything, you can’t have a treatment, and you can’t have awareness. Alejandro, you built a nice program at your institution [University of Virginia School of Medicine]. I want you to comment on this. How does it work with dermatopathology? Talking to the dermatologist and the clinician, how do you coordinate things in these complex cases?

This is critical. Communication is the most important thing for these cases. When I work with my fellows, we get a case of possible leukemia cutis or 1 of these entities, someone might come in healthy, without any other symptoms. I had a patient who had just 1 little lesion on the face that looked like a basal cell carcinoma. You explain to your colleagues, you call the team and the clinician, “Listen, this patient has the equivalent of a new diagnosis of leukemia.” This patient needs to be seen right away, needs to go to a hospital right away, or needs to be seen by hematologists right away. While you’re working on your biopsy, you need to make sure you have all the right markers. Some of these markers aren’t available in all community dermatopathology labs. Some markers might be more esoteric. If you ever think about this, either consider doing these markers or sending to another referral center that might have the extra tools that you want to work with.

This disease is going to require aggressive treatment, and many times chemotherapy. Share this case with the hematopathologist who has the expertise from leukemia, who has expertise in AML [acute myeloid leukemia] and lymphoblastic leukemias. You want to make sure you have a strong interaction, you work as a team, you interact thoughts, and you have a rapid diagnosis so you can direct a patient correctly.

Once I had a case where a biopsy was sent to me with a patient who had an isolated lesion of reactive plasmacytoid infiltrate. Somebody thought they had reactive plasma cells on the skin or evidence of myeloma on the skin. Myeloma isn’t necessarily an extreme urgency like this is. With these patients, most are going to have leukemic involvement by the time that diagnosis is made. It’s critical that you communicate, especially when you’re talking about clinicians, dermatologists, or family practitioners who often do biopsies. You need to emphasize the rush need to have this patient seen by a hematologist, by an expert physician who has experience, to make sure the right work-up is done and that this is done in a timely basis.

If you remember the literature on some presentations, there was a significant delay between the first time the patient presents to the clinic and the time when a final diagnosis is made, of sometimes 4 months. These patients don’t have the luxury of having months. In a lot of these patients, if they don’t get referred promptly, they’re going to die from the disease. It’s critical that communication is the key word, in terms of the management of these patients.

This is awesome. It flows nicely into the next topic, which is that the other key members of our multidisciplinary group and are the stem cell transplant folks. James, we know transplant is a curative modality in many aggressive malignancies, such as BPDCN [blastic plasmacytoid dendritic cell neoplasm]. I regularly transplant patients, but a lot of our patients are old or frail. This is 1 example of our own data set. The median age was 39 or 40 years old. We’re transplanting patients in their 70s routinely. You and I are advocates of stem cell transplant when we believe it’s curative, but there are barriers. How are you thinking about transplant in BPDCN these days, James?

It’s a goal for all our patients. It’s important to keep that in mind because it affects what we’re doing at the beginning. As someone who doesn’t do transplant, I always like drive this home to my transplanter. I think, “Give them the CR [complete remission], and we’ll take it from there.” But that’s not the answer. Not all CRs are created the same. We want a good-quality CR. We want to take a person through that and get them into CR in a shape so they can go to the transplant to tolerate that well.

That’s part of our job: to start working on that promptly, looking at our options for transplant and preserving their performance status. As we arrive at the door of transplant, we’re reassessing where we are. Just as we’ve seen in many other diseases, the quality of the remission is important as we start to plan transplant and the likelihood that it translates to help our patients. It ends up becoming a personal decision for many of our older patients. What’s the benefit of the transplant? What’s the trade-off in terms of toxicity? What might they sacrifice for that small benefit in some patient populations?

Comprehensive insight on the sequencing of agents in BPDCN management, followed by considerations for use of stem cell transplant in this setting.

Sequencing Therapy in BPDCN in the Second Line and Beyond 

Great discussion thus far. Let’s go to our third, and I believe our final, case for this program. This is going to be a little bit more of a real-world situation here. We have a progressive disease situation. This is a 57-year-old man who has confirmed BPDCN [blastic plasmacytoid dendritic cell neoplasm], very good ECOG [Eastern Cooperative Oncology Group] performance status of 1. In this case, [he] received yet another different regiment, an AML [acute myeloid leukemia]-based standard 3 plus 7 regimen, as a frontline approach. Initially, while he did achieve a complete remission, a CR1 [first complete remission], this was found to be only less than 6 months so it was deemed to be an important case of an early-relapsing patient.

This patient presents to you in clinic with good performance status, good discussion, and not a whole long list of standard therapies. You discuss certain options such as tagraxofusp, clinical trials, further chemotherapy, venetoclax, hypomethylating agents, all the things that we talked about. The first question for Dr [Alejandro] Gru is actually an important question that I was looking forward to asking you. Sometimes we notice our patients with BPDCN will respond in one compartment but progress in another. [For example,] a bone marrow response but the skin is coming off, or the skin response but a lymph node is growing, and the biopsy is clearly showing BPDCN.¼ What are your thoughts, what are you thinking about? Are these different sanctuary sites? Is this the same disease? Is it spread out all over the place? How come if it responds in one area, Alejandro, it doesn’t in the other? What are your thoughts there?

This is a very interesting and a very peculiar question that keeps us awake all night trying to understand why this happened. What is interesting is, I think there’s been some molecular data that if you look at different sanctuaries, you’re going to see a somewhat similar base of molecular alterations at the genetic level, looking at copy number changes or looking at mutational profile. When they start on the skin and they progress into the bone marrow subsequently, sometimes you see the acquisition of new copy number changes, new mutations, etc., that were not seen before.

I will say this is very interesting because we had a recent case where the patient had bone marrow disease and had skin involvement, both showing a similar BPDCN-like phenotype. Interestingly, there were some peculiar differences in the molecular landscape. There were some differences in the copy number changes, one has more copy number alterations than the others. So it is critical, and what you say is actually true, that it is very likely that perhaps different compartments might show evolution of different levels and might gain or lose certain alterations that make the tumor more suitable to grow in that environment but not in the other. Perhaps the chemotherapy, or targeted therapy, can actually target well in one area, but not necessarily well in the other. [The disease] might acquire subsequent alterations that make it less responsive to that. I think that’s an area that it’s so difficult to evaluate given the rarity of the disease. It’s so critical to have enough cases where you analyze biopsies at different time points in life, and trying to understand why there is progression in one place and not in the other. But I think that’s a fascinating question, and that is something that is really going to help to direct treatment to these patients.

That’s awesome. It’s exactly the scenario we face. I didn’t put it in the description, but that’s exactly what happened, there was some progression and mixed response. We had a discussion, and the decision was discussed [if it should be] clinical trials, again with the IMGN632, which now known as pivekimab sunirine. The patient opted for standard of care, [and] in that case, there’s only one left, tagraxofusp, which the patient did not yet have in the front line.

Centering discussion on the third patient case, panelists review second-line therapy options for those who relapse with blastic plasmacytoid dendritic cell neoplasm.

Patient Case 3: A 57-Year-Old Man With Relapsed BPDCN

Gentlemen, let’s move into case number 2. Very exciting discussion so far, I’m actually learning quite a bit from both of you. This is a 22-year-old female. She presents with bulky lymphadenopathy and some skin lesions. They’re maculopapular in nature, across the face and trunk. Initially, it was thought to be that maybe she was going to have ALL [acute lymphocytic leukemia] or lymphoma, but then bone marrow shows 48% blasts. CD123-positive 456, and one of the new markers, TCL1, and TCF4 all positive. I can tell you this patient had classic newly diagnosed BPDCN [blastic plasmacytoid dendritic cell neoplasm]. Interestingly, because it was a young female, BPDCN was not on the radar, thinking that it should be an older male disease. As both of you mentioned, awareness is the key.

So young female, BPDCN diagnosis. I wanted to turn it to Dr [Alejandro] Gru again. I really think this is important, what you both said, about the awareness model and algorithms. Dr Gru, you get so many cases. How is somebody supposed to think about a rare disease when it’s not even the right demographic? What are your thoughts on that? How do we train our fellows and our staff to recognize this?

I think those are excellent questions, and you’ve made some excellent points. In a young patient that has perhaps multiple skin lesions, multiple skin nodules, the first thing that is going to come to mind¼if I’m thinking about someone who has blasts in the bone marrow, it’s going to be a lymphoblastic leukemia. That is usually going to be the most common diagnosis we’re going to find. Just a few weeks ago I had a child where the skin biopsy was the first time that he was diagnosed with the B cell-ALL, and then we immediately have to send the patient to the ER [emergency room] to have him further evaluated. So understanding that this disease is not restricted to adults: There are 2 main peaks. There is a peak that happens between the age of 70 and 80 years of age, but there is also a peak that happens in younger patients. Sometimes you can even see patients who are less than 10 years of age. So that’s number 1.

Number 2, it is important to understand that some of the immature markers that you see in lymphoblastic leukemia, that sometimes present on the skin, can also be seen in BPDCN. For example, TdT, which is a prototypic marker seen in lymphoblastic leukemia—either B- or T-cell lineage—is seen in a proportion of cases of BPDCN. About 30% to 40% of cases. It’s interesting, if you look at the literature, perhaps those might even be cases that do better prognostically than conventional BPDCN cases. So it is important to have that in mind.

Another thing that is also interesting is that some cases of BPDCN do not have that classic blastic morphology that you see with more common acute myeloid leukemias [AML] or acute lymphoblastic leukemias, where we would have blasts that are intermediate size and have fine chromatin, but actually they will have an immunoblastic appearance. And this is a variant that is rarely seen here in the United States, but it was actually described by the Japanese team. They have this immunoblastic morphology resembling a diffused large B-cell lymphoma, and these cases have a MYC translocation similar to what you see in other entities, similar to if you saw B-cell lymphoma or Burkitt lymphoma. So I think it is critical when you have a young patient with multiple skin lesions, something that look like blasts, that you go over your differential, thinking about the most common things, which is the lymphoblastic leukemia lymphoma, but also still keep this rare disease in your differential to make sure you do an accurate immunophenotypic evaluation in the biopsy.

Wonderful. So building on those nice comments you laid out for us, the diagnosis was confirmed as BPDCN. Now, turning to James, the team was unable to acquire the CD123 agent for various reasons. The patient was dutifully treated with hyper-CVAD-based chemotherapy and got her LPs [lumbar punctures] done. She also achieved complete remission after the part A and part B. Just to remind people, methotrexate–Ara-C (cytarabine) is the part B, as you and I are well aware. Now the question for you is shown here. We’ve had 2 nice cases, an older fit person, a younger fit person. Two pretty different programs, both achieving CR [complete remission]. Here’s the million-dollar question for you and me, James. How do you choose between an older and a newer regimen? There’s not going to be any randomized control data in these small groups. What are you doing in your practice? Is it basically individual situations, tumor bulk, age, are you trying to get to a transplant? What are your thoughts on that?

It truly is incredibly challenging. I think we’re all fortunate for the work that you’ve done, because some of your retrospective data looking at the outcomes of patients have been helpful. First and foremost, we should point out that this is a young woman who, honestly, was not well represented by the patients who enrolled on to the clinical data we have with Elzonris (tagraxofusp). The median age there was around 72 in the first 3 cohorts. The youngest patient was really in their 40s. So she’s a challenging patient. We don’t have a lot of concrete data to go upon. But some of the retrospective data out of [The University of Texas] MD Anderson [Cancer Center] have really shown that these younger patients, as you alluded to earlier, do seem to be more chemotherapy-sensitive. Additionally, these are patients who typically tolerate multi-agent chemotherapy at the full dose.

For us, I think, this is a lady who has bulky lymphadenopathy. Certainly, there is an appeal, in my opinion, in getting drugs that really penetrate the CNS [central nervous system] as well. Especially if we think of this as a reservoir for possible relapse. So these young patients, while there is still some gray area in terms of the best treatment, are folks whom we might look at as more suitable for multi-agent chemotherapy as a bridge to transplant.

Wonderful. This brings us to that question about toxicities, as you nicely mentioned. That’s certainly a part of what we think about. You may have a patient with some mild or major cardiopulmonary abnormalities or albumin issues. That may steer you away from the CD123 therapy. Bulky lymphadenopathy may be a concept of you wanting immediate tumor debulking in an emergent situation. Proliferative white count, maybe that steers you towards cytotoxic. I really love that.¼[And] just to remind people, I am admitting patients for hyper-CVAD-based chemotherapy for induction and really for the subsequent cycles. As you would do in a high-risk ALL. Watch out for tumor lysis syndrome, watch out for infections and sepsis, watch out for myelosuppression. So here it was cytotoxic effects. Also, what’s the performance status [PS] going to be, James, heading into the stem cell transplant? One of the advantages with the tagraxofusp has been people maintaining their PS. Have a good team, follow those labs, inpatient and outpatient, closely. Any fever, go to the emergency room. Good ALL, AML management in that setting is important.

Expert panelists review the case of a 22-year-old woman diagnosed with BPDCN and consider the role of first-line chemotherapy in this setting.

Patient Case 2: A 22-Year-Old Woman With BPDCN 

From the clinical standpoint, and I’ll answer this for us, what do you do about the capillary leak syndrome? How do you determine what to do? Dr McCloskey was giving us a really nice overview, and is exactly right. You look at the performance status [PS] or the fitness. With the tagraxofusp agent, the baseline albumin does matter, and there is guidance for the numbers. It’s what we used in the clinical trials. You want to look at the cardiopulmonary status, the ECOG PS, and the albumin. If you have availability of tagraxofusp, as you can see, it’s an FDA-approved agent. But a lot of patients are older, unfit, or you don’t have availability, cost, or access.

So [our group] and other groups, have used ALL [acute lymphocytic leukemia]-based regimens such as the hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, and dexamethasone]…regimen, and add venetoclax if you have it. Older, unfit [patients will get a] hypomethylator plus venetoclax, so azacitidine or decitabine. Other groups around the world have used lymphoma regimens, or AML [acute myeloid leukemia] regimens. There have been some varied approaches. In the pediatric setting, which I’m starting to have more experience with because we’re getting calls from all over the world, it does appear to be a slightly different disease in some of these children than the adults. As usual, they seem to be a bit more chemotherapy-sensitive. So again, you can use the tagraxofusp agent, which is approved in that setting, hyper-CVAD, ALL-based regimens, and then as James nicely mentioned, allotransplant in CR1 [first complete remission] if your patient is fit. That is just to put it out there, that there are other strategies. Then there are lumbar punctures for central nervous system disease, and maybe a consideration of maintenance after.

I think we’ve talked about this already, but I want to get your take. One question to ask on the tagraxofusp, SL-401, or Elzonris, James I’ll ask you, what are your impressions 3 or 4 years later? We have this drug, we have a feel now, and we have discussions like this. What do you think, what’s the future for BPDCN [blastic plasmacytoid dendritic cell neoplasm] and this drug?

I think this is an exciting new agent in this field. More than anything, having a drug that’s specifically approved for this disease, the only drug approved in this disease, has raised awareness. I think that’s one of the reasons a lot of people are highlighting it and talking about it, because we treat it differently now. Not everyone gets induction therapy with multiagent chemotherapy.

In this older patient population we saw in this study, which really represents your day-to-day patient with BPDCN, these are impressive CR rates, and they appear durable for some patients. Most of these patients are going to relapse, but they do appear to be CR rates that look superior to what we’ve seen historically with chemotherapy in older patients. Again, particularly in these elderly patients, it can be hard for those patients to tolerate full-dose hyper-CVAD. So I think there are a lot of other exciting therapies in development. As we start to borrow from drugs approved in AML that might have even more favorable toxicity profiles for elderly patients, that will be an exciting option. Figuring out how to maintain these patients in a remission once we get it is key.

That’s great. The final question for this case, I’ll address for us, which is are there other adverse events? We mentioned the capillary leak syndrome: potentially fatal, black box warning, 18% to 20%, you need to know about that. The second and third issue are usually all restricted to cycle 1. On the study and in the real world, we do see thrombocytopenia in about half the cases, and increased in LFTs [liver function test] levels, AST [aspartate transaminase] and ALT [alanine transaminase] in particular. Usually its restricted to cycle 1, the first 3 to 5 doses, and then very rarely after that do you see any of these toxicities. Interestingly, we do not see very much neutropenia or neutropenic fevers, so it’s not a cytotoxic agent with hair falling out, or a lot of nausea and vomiting. That’s important.

I usually do admit patients. I admit them for the first cycle for sure, you have to do that. Watch out for the capillary leak, albumin. I also usually end up admitting most patients for subsequent cycles. Of course, you can do this as an outpatient treatment. Watch that albumin. Then you don’t have to do all 5 doses, days 1 through 5, in a row. It’s built in that you can take a break. Look to see if there’s too much weight, then you can do diuresis. I think these are important. I’m proud to tell you that what’s on the package label insert is basically what we did on the trial, so maybe have a pharmacist and a health care team following the patient with you.

Closing out their discussion on the first patient case of BPDCN, panelists consider which factors best inform the optimal selection of frontline therapy. 

Naveen Pemmaraju, MD | Authors

Articles

BPDCN: Future Directions in Care

Emerging Therapies in BPDCN

Sequencing Therapy in BPDCN in the Second Line and Beyond

Patient Case 3: A 57-Year-Old Man With Relapsed BPDCN

Patient Case 2: A 22-Year-Old Woman With BPDCN

Factors in Selecting Optimal First-Line Therapy for BPDCN