Marlise Luskin:

Good morning to everybody. My name is Marlise Luskin. I’m at the Dana-Farber Cancer Institute at Boston, Massachusetts in the division of leukemia. We’re really happy to be having this discussion today about a diagnosis called blastic plasmacytoid dendritic cell neoplasm, which we’re going to break down and talk about what it is and how you diagnose and how you treat it. This is a discussion that I’m glad to have with colleagues, Dr Shimony and Dr LeBoeuf. Have you introduce yourselves?

Shai Shimony:

Hi, good morning. My name is Shai Shimony. I’m also part of the leukemia team here at Dana-Farber Cancer Institute and very happy to join this discussion today.

Nicole LeBoeuf:

And my name is Nicole LeBoeuf. I’m a dermatologist at Brigham and Women’s Hospital and at the Dana-Farber Cancer Institute in Boston and work exclusively in the Cancer Center trying to support the research efforts of folks like Drs Luskin and Shimony as well.

Marlise Luskin:

All right, well, let’s dive in. So this discussion is about a diagnosis called blastic plasmacytoid dendritic cell neoplasm, or BPDCN. And this is a mouthful of a name, and this is a diagnosis that is quite rare. And so we are really happy to kind of bring attention and awareness to this rare diagnosis because there’s a lot we can do for patients if we diagnosis them in a timely fashion. So let’s start off with what it is. So briefly, this is a rare leukemia that has features that are similar to both leukemias and lymphomas. So I always break it down for my patients. I said neoplasm means cancer. The cancer cell is a transformed dendritic cell, and that term, blastic plasmacytoids, describes that dendritic cell that has gone rogue and spread inappropriately through the body. And so a unique feature of this disease is that it can involve multiple parts of the body. Just like leukemias, it can involve the bone marrow and the blood, just like lymphomas it can involve lymph nodes and spleen. But a really unique feature of this diagnosis that is often presents with characteristic skin lesions and so patients come sometimes to the leukemia or the hematology clinic but often they come to us originally through an evaluation by a dermatologist. So, Nicole, maybe you could tell us a little bit about what you see when you first meet a patient and what might be a range of typical presentations

Nicole LeBoeuf:

Sure thing. I think one of the most interesting things about BPDCN in the skin is many patients present with these very characteristically deep, deep purple skin nodules. And they’re really a color like nothing else. Now, BPDCN can present with skin colored nodules or pink bumps that may be single lesion, multifocal a couple bumps, or it could be disseminated all over the body right at presentation. But this deep, purple color is really characteristic. So when you have a patient who has these sort of you know infiltrated bumps on their skin as dermatologists we often ask questions about whether we think it’s a B-cell lymphoma of the skin or a T-cell lymphoma of the skin but anytime we see that really really rich deep deep deep purple color like plum, plum purple color, it is almost always BPDCN. So you can have BPDCN that isn’t purple, but when it’s purple, I have yet to encounter a patient where it wasn’t BPDCN. So it’s really one of these diagnoses where an outside dermatologist or an oncologist will send in a patient for a, quote, “cutaneous lymphoma”, and I’ll see a picture of a purple, looks like a plum stuck on a head, and I immediately reach out to my team and say, I think I’ve got another BPDCN coming in because it’s almost pathognomonic when you see that deep, deep, deep purple plum color. So again, folks may come in with single lesion, you know, focal tumor. And oftentimes what we hear is that the skin lesions precede any systemic symptoms. So they have this bruise. They think they always say, oh, I bumped my head or I whacked my arm, and they sort of have come up with a story for how the bruise began. And then over weeks or months, it will thicken up. And then usually there’s a delay to when it does spread. There’s one interesting thing that we’ve been looking into in terms of the presentation on the skin and the pattern of spread. And that’s an observation we made that the way that it likes to spread in the skin is similar to a condition in dermatology called pityriasis rosea. And many physicians heard about this in medical school, the Christmas tree pattern on the back is the sort of diagnostic pattern of PR. And it turns out that BPDCN, when it disseminates diffusely, always spreads in this Langer’s Lines or Christmas tree pattern as well. So if you walk in a room and you see a person with a purple nodule anywhere and they have nodules or bumps in a Christmas tree pattern, it’s almost always BPDCN. And when it’s not, it’s AML. So it’s still concerning, but that purple nodule sort of pushes you into the BPDCN space. So that’s what we see clinically and that sort of guides how urgently we evaluate the patient or what we talk to our pathologists about in terms of our concerns.

Marlise Luskin:

Well, great. Thanks for that description. That was really crystal clear. You touched on a few things that I was hoping Dr Shimony could add to. So number one, the latency between an initial lesion and diagnosis and the common story that you sort of described of a bump on the head, a bruise, or I’ve heard bites or something that somebody thinks is in the realm of sort of a normal lesion that will disappear and the delay in diagnosis. And then also the range of presentations that patients have in terms of involvement of the skin versus other tissue compartments. Shai, could you talk about those two things?

Shai Shimony:

Yeah, sure. Gladly. So first, of course, completely agree with Nicole about the presentation, the bump and the delay. In our cohort when we looked on all our PDCN patients and often we see even three to four months. The median was around four months between the first symptom, the first bump on the head, the plum on the head, until the diagnosis is made because of delay either in the community or within local pathology that didn’t send the CD123 or because of this rarity of this disease. You need to think about it in order to diagnose it. Besides the skin that is, in 50% of cases, is the only organ involved at diagnosis, bone marrow is often involved as well. And we also see the lymphoid tissue, spleen. We tend to see sometimes an oropharyngeal involvement as well, if we’re talking about besides the skin and the bone marrow. So there’s also an oropharyngeal involvement. And CNS, the central nervous system, is also often involved. And this is something we just recently discovered in the last couple of years. So CNS, both at diagnosis and at relapse, is a major component when people are diagnosed with BPDCN.

Marlise Luskin:

That was great, Shai. Thanks so much. I think you alluded to something maybe that we can segue into about, you know, thinking about this diagnosis. And so..

Nicole LeBoeuf:

Marlise, could I add one quick thing about the oral? So it definitely affects the mucosa. So again, I think as dermatologists, we learn about gum lesions from AML. It’s sort of like the thing, the place to look. BPDCN definitively like makes these purple nodules, even on the gingiva. But we’ve seen it on the palate. We had a patient with throat symptoms like sore throat and had a big nodule in the posterior pharynx, but also other places. So we have patients with lesions on the cervix diagnosed as like dysfunctional uterine bleeding. Just the patient that we saw this week, a conjunctival, big old purple nodule within the conjunctiva. And these are areas that are important, not only at, you know, it’s maybe less important at the time of diagnosis because they have lesions everywhere and they’re diffuse disseminated disease. But it’s absolutely critical, we’re going to talk about follow-up later, but to understand where it goes, because if you don’t look in the eyes, look in the mouth, you know, look at the mucosal surfaces, you can miss the early relapse at the mucosal site first. So it’s oropharyngeal, but it’s also every mucosa. And so now our full skin exam is like full skin, lymph node and popping everything open when we see these folks.

Marlise Luskin:

Exactly. And that, you know, any physician can certainly do a full skin exam, but certainly our dermatology colleagues have some expertise in the sort of subtle findings that might be there. So I want to touch on two things first. You know, we’ve sort of talked a lot about the clinical presentation. I think we should mention before we go too much farther, sort of the classic demographic of this disease. I can maybe just sort of chime in here. There’s a very interesting sort of demographic in that the majority of patients that are diagnosed are men in their 60s and 70s. And there’s a strong male bias so that the majority of patients four or five to one are men. So if I look at my list of patients that I’ve treated with BPDCN, almost all of them are in this specific age range and gender demographic. So when we hear a story about a lesion with this sort of scenario that we discussed, particularly when they’re in that right demographic, we really think about this diagnosis. There is also an entity of pediatric BPDCN that’s even more rare. And in that case, there’s different biology, which we can get into in a little bit. But in that case, there’s not that male bias. It can happen in both boys and girls in the pediatric space. So you guys both, Shai, you mentioned this 123, and I know, Nicole, we’ve talked about this before. We’ve already talked about the involvement of both a hematologist and a dermatologist, but pathologists are really important. All of us have to be thinking of this diagnosis, a hematologist, a dermatologist, and a pathologist when they get a sample to the lab. So, Shai, do you think you would want to chime in a little bit about pathology? And then I’ll pass it to Nicole.

Shai Shimony:

Yeah, sure. So in the recent WHO classification, in order to diagnose BPDCN, you need to go with flow cytometry or immunohistochemistry to look for the 123 which is actually present in all BPDCNs. That’s the hallmark of that; other markers are that are common are CD4 and CD56 – this is why we call it CD123456. And in addition you need pDC markers like TCL1, TCF4 that are more specific. So in order to diagnose, you need a classical hallmark with pDC hallmarks and the absence of the classical myeloid or lymphoid lineage-defining markers like MPO or CD19 for B-cell ALL or CD3 for T-cell ALL.

Marlise Luskin:

Thank you, Shai. I know we interface a lot with hematopathologists, but particularly at large centers where there’s a specialization, the pathologist also first reading this as a dermatopathologist. Nicole, maybe comment on how you approach that.

Nicole LeBoeuf:

Yeah, so I think even beyond dermatopathology, there are many places where general pathologists are reading skin slides throughout the country. So we have a couple issues where we have delays into getting access to dermatologists in the first place. And then the patient shows up to the dermatologist, does the skin biopsy. And without the guidance to the pathologist in the community, the CD123 stain is just not often done. So, you know, our work in dermatology is actually to get out there and remind dermatologists that this disease exists, that 50% of the time it’s in the skin only first, like Shai told us. And when we put it on our requisition, we have to not just say like rule out lymphoma. We have to specifically say purple nodules, check CD123 for BPDCN. And so we articulate that very clearly here, even though our folks are usually thinking of it. But even at this institution where we have a tremendous BPDCN center where we’re thinking about it, we sometimes don’t get the stain done because things aren’t perfectly classic. So I think it’s on the dermatologist to really make sure they’re articulating leukemia cutis, rule out BPDCN when they see those plum nodules or AML versus BPDCN, or even just to know that it exists to really prod the pathologist. Because otherwise that delay, you know, a recent patient we saw had like a seven week delay because of the sequential immunohistochemical stains that were done before the diagnosis was made and they were referred in. So if everyone’s thinking about it, the diagnosis can be made very, very quickly. So it’s kind of on all of us to continue to push this forward. And I know, you know, it’s made a presence in the dermatology journals as well. So really on us to sort of ask for it.

Marlise Luskin:

…Due to some of your efforts. So thank you for that. You know, one of my favorite stories is that one of my recent patients, you know, lived in a part of the country that was a bit more rural and distance to specialists was a little bit more challenging. And his family medicine doctor like saw these lesions and kind of figured it out and did the biopsy herself and communicated with the local general pathologist and made a diagnosis really rapidly. And I gave her major, major props for that because it was really impressive to see. So building awareness across all specialties for this unique diagnosis is important. And that’s why we’re here today. Maybe just, you know, touch a little bit. We want to really move into how we treat patients and monitor them because that’s the most important for those of you at the bedside. But just to mention that Dr Shimony, in collaboration with Dr Andrew Lane at our center, who really has been leading research efforts, along with Nicole, who’s here with us today, have been really spending a lot of time sort of learning about the intricacies of the biology of this disease and really identifying some unique features. Certainly there’s things I find interesting, but maybe I’ll let Shai, maybe if you want to highlight anything in particular, and before we move on to taking care of the patient.

Shai Shimony:

Sure. So I think one very interesting point on the pathogenesis of that, of BPDCN, is the involvement between the bone marrow and the skin, not only in the presentation, but also in the level of pathogenesis. A model that was presented and studied and published in Nature recently by Dr Lane and colleagues showed that the pDCs actually have usually a TET2 mutation they acquire in the bone marrow which gives them an advantage. They migrate to the skin, they acquire through UV sun exposure, additional UV typical genetic mutations, either RAS or CDKN2A mutations, and then they might re-migrate to the bone marrow where they proliferate and promote the systemic disease. So this pattern of migration to the skin and re-migration through acquisition of a UV mutation is very unique. And we did not only see that in the biology level, we also looked on it in the clinical setting where we evaluated the relationship and the association between UV exposure and skin lesion in BPDCN patients and we found that patients with skin lesions had higher rates of TET2 mutations, whereas those without skin lesions have fewer TET2 mutations. So the clinical presentation really associates with the biology underneath. That’s one thing. And the other thing that we’ll maybe talk afterwards is the prognostic value of these, both mutations and clinical presentation that we found to be contributing to the prognosis of our patients.

Marlise Luskin:

Thank you, Shai. Nicole, anything you want to chime in there about the role of sun exposure and the biology?

Nicole LeBoeuf:

Yeah, so I think only that it’s just such a tremendous privilege and honor to work with our team here, with Dr Lane and you guys, because that discovery, I think, was made over years of collaboration and observation, right? I think the very first patient I saw with BPDCN had a purple plaque at his Mohs surgery site of his squamous cell carcinoma. So we kept seeing the same pattern. And so I don’t know that, you know, the men over 70 are the ones who are also getting skin cancer, right? So it’s the clinical observation and really acknowledging the zebra of a diagnosis and asking a million questions of these patients, where they live, where they grew up, where they spent more than five years, so that we were able to collect this data over a decade, not knowing what was going to come of it, but making these clinical observations and having really tremendous collaborators where, you know, I just give tissue to Dr Lane’s lab. The patients have been tremendous. The patients are so generous, right? Because it’s a rare diagnosis. And so having these really invested patients and these really invested investigators and then saying, this one looks different, the pattern is different, the timing is different, and having all those pieces over time and space and treatment is what I think allowed Dr Lane’s brilliance to come to this conclusion, and none of us would have been able to do it alone. So it’s just such an honor to work in such a great multidisciplinary team, and I think it highlights not only how we can help our patients, because I’m not sure we’ve made enough progress in improving prognosis and clinical care of these folks, right? We still have a ton of work to do in curing more folks, but we’ve made a lot of progress in starting to pick apart what the heck’s going on. So clinical observation leading to scientific discovery, I think is really such a … approach.

Marlise Luskin:

That’s a great segue into let’s talk about treatment and then we’ll go back to prognosis. As you mentioned, we still have work to do, but fortunately we have had some progress. So, you know, so just to recap for BPDCN, think about it when you have particularly a male in their 60s and 70s, but of course, don’t rule it out with other demographics with a characteristic purple lesion. Think about it, send a biopsy to whatever pathologist you have available to you. Make sure that you highlight your concern and the need for that 123 stain. Once a diagnosis is made, make sure you sort of complete staging. Again, we look at all those tissue compartments. So we do a bone marrow biopsy. We check the blood. We do a baseline LP and look for any CNS involvement. That was another observation that’s been made over time that this disease involves the CNS. And if a patient has not already seen a dermatologist, particularly one with experience with BPDCN if possible, to get that full sort of baseline skin exam. So we sort of define where the disease is at the beginning, but when I tell patients, I say, this is just so us, also we do cross-sectional imaging, PET-CT or CT if possible. But I tell patients, you know, the disease is a systemic disease, even in those cases where we see just one spot on the arm or on the head, it might be just this tiny thing. I say, even though it’s tempting to just to try to remove it, like you might another type of skin cancer, we know that this is a systemic disease as Shai pointed out. So we need to treat these patients systemically. In terms of how we approach treatment, I always tell patients our first goal is to offer chemotherapy, some sort of medicine to try and get rid of all detectable BPDCN cells in all the tissue compartments, get that patient into a complete remission, and we’ll talk about that. And then for remission, we want to make that remission as durable as possible by either continuing treatment in a sort of maintenance fashion or in patients who are eligible, we do know that for patients who are eligible, the best chance of a cure is by applying allogeneic stem cell transplant in first remission. In terms of initial treatments, we’ve really historically not had anything. Given the rarity of the disease, we didn’t have specific treatments available for BPDCN. And over years, individual hematologists, oncologists, maybe you’ve seen one or just a couple cases in their career would give patients a treatment adapted from AML, acute myeloid leukemia, ALL, acute lymphoblastic leukemia, or lymphoma. And often patients would respond. We have relatively in the last few years, Dr Lane with Dr Taylor, who was at Memorial Sloan Kettering at the time, did a review of outcomes from patients and treated historically. And it was seen that patients who receive intensive ALL-style chemotherapy regimens did have the best outcomes. This may be due to the sensitivity of the disease to those drugs. It may also relate to the fact that ALL regimens do incorporate CNS prophylaxis, a tissue compartment that was not recognized but may have been treated by the ALL. Now, going forward, I tell patients we have expanded options, two to highlight. One is, of course, we would be remiss for not highlighting development of a drug called tagraxofusp, which is an anti-CD123 targeted agent. Remember, all BPDCN expresses 123, so it’s really targeted to these cells, and it’s conjugated to a diphtheria toxin. This is a really unique drug that Dr Lane and colleagues developed specifically for this disease, and it led to the first FDA approval for BPDCN. This drug is unique and also has a unique side effect called capillary leak syndrome, and this requires patients to be admitted to the hospital for the first round of treatment for close monitoring and management with specific guidelines that are outlined by the protocol or by the package insert. This is a drug that can be given safely to most patients, but they need to be selected appropriately to minimize their risk for life-threatening or fatal capillary leak syndrome, including having sufficient cardiopulmonary function and normal ejection fraction and having a baseline albumin that is sufficient. That’s a really important option for many patients. Another really important new option for patients is a drug called venetoclax, a BCL-2 inhibitor. This drug has been developed for chronic lymphocytic leukemia, lymphomas, and notably acute myeloid leukemia, or AML. And this drug was being developed for sort of closely related but different diagnoses in our hematology space, but we were familiar with the drug. And Dr Lane, again, in the lab using samples from our generous patients, really identified the sensitivity of BPDCN to venetoclax. And so we have now had experience treating patients with this drug by itself and in combination with a hypomethylating agent, another drug that’s used in AML. And that combination has been an effective option for patients and also a very well-tolerated option for patients that may not have as robust organ function, again, in this older population. Of course, we’re always trying to make things better and there are ongoing clinical trials. There’s interest in developing other CD123 targeted agents. I won’t go into details, but there have been some trials ongoing, and we hope that there will remain interest in our academic community and our pharma community as well to further pursue those. And then another sort of pursuit that we’ve undertaken here at Dana-Farber that we’re excited about is combining some of these effective treatments together. So we are actively recruiting to an ongoing trial combining azacitidine, a hypomethylating agent, venetoclax and tagraxofusp, that CD123 targeted agent. The trials ongoing, we’ll be looking forward to reporting it in the not too distant future, but I can say we’re certainly encouraged by the results. So that’s sort of an overview. Again, make the diagnosis and then sort of consider those treatment options for the patient whenever possible, given the rarity of this disease we do try to enroll patients in clinical trials. Patients generally, again, are very interested in having access to those trials and contributing to our knowledge. But of course, it’s not always an option for every patient. And then we select an ALL-type or an AML-type or a tagraxofusp-type chemo to get into remission and then consider allogeneic transplant in first remission for those who are eligible. Shai, any other comments for treatment that you’d like to highlight and then maybe segue perhaps into prognosis or risk verification?

Shai Shimony:

I think this is an excellent review. I would just maybe add that the remissions that we achieve usually with BPDCN are very short. We also see it in our data in others as well. So, the process of trying to find a donor for those who are eligible for transplant should be as early as possible. And once they get into the remission, trying to get this immunotherapy or transplant working because at least in our data, the remissions are around two or three months – the median is two or three months, which is very short. And one other thing to remind about post-remission relapse, if they occur, they usually occur similar to that first presentation. So if patients usually presented with skin lesions – you should always look for skin lesions when you evaluate, skin and mucosa lesions – but those who presented with skin lesions usually tend to present at relapse with skin lesions and vice versa those who present with only systemic disease usually present with cytopenias and bone marrow involvement rather than skin involvement.

Marlise Luskin:

And I think another fact that you’ve shown, Shai, is that patients who have a skin-only disease tend to, in the range of the durability of remission, those patients tend to have a better prognosis than patients who have more involvement of the body with multiple tissue compartments. It doesn’t mean that you shouldn’t treat those patients aggressively because we know over time the disease will progress, but they do seem, you know, identifying patients early and getting them on treatment does seem to improve their prognosis.

Nicole LeBoeuf:

One thing –

Marlise Luskin:

I was going to say, Nicole, let us know what do you think about how you stay involved with the team over time and detecting relapses and early relapses?

Nicole LeBoeuf:

So even before the relapse situation, is determining complete response. In our cutaneous lymphoma and cutaneous T-cell lymphoma world, the clinical presentation is so different. If I were to think of a more common diagnosis that BPDCN resembles a little bit, maybe your PTCLs with some skin involvement, where it’s deep. What we see in these folks is that our chemo regimens work great. Things melt away fast. The big purple plum regresses quickly. And then you’re left with this brown hyperpigmented patch on the skin. So most of the time, the skin doesn’t look normal. And you want to go into transplant with an absolute minimal disease or no disease, right? We truly want a complete response for patients to have the greatest likelihood of a good outcome. And that’s basically true across all our diseases that we transplant for. But for BPDCN, you’re looking at a brown patch, and there’s no way to know with your eye if it’s truly gone or if there’s MRD. And so, again, in most of hematology, oncology, there’s no paradigm for this, right? You do bone marrow biopsies or you do a PET scan or you have your plan in place for how you assess for residual disease based on the malignancy. In BPDCN, we oftentimes need to do that biopsy. So in the clinical trials, our mSWATs are this tool, this modified severity-weighted assessment tool we use for cutaneous T-cell lymphoma clinical trials to sort of measure how much skin disease you have and whether it goes away. Your mSWAT doesn’t go to zero if you have anything on your skin. So we’d had all these patients who had active disease, but really it was just post-inflammatory hyperpigmentation. And so we biopsied them to prove whether they were CR or not CR. And we were often surprised that even in patients where they looked like they had a complete clinical response, there were still a few CD123-positive cells in that skin. And so you may need to treat a little longer than you think, or you may need to do that biopsy or get someone to do that skin biopsy for you as part of your evaluation for true, complete clinical response, or you might miss it. And those may be the people we’re going to work on figuring that out. Those may be the people who have that early relapse post-transplant. And so quickly after transplant, again, it’s not just a skin exam where you’re like, lift up your shirt, get naked, put them in a gown. If you don’t have access to a dermatologist, put them in a gown, put them under the light. And you’re literally, I tell them, I’m like, I’m sorry, I’m giving you a little massage because those nodules can appear under the skin before they look purple. And so it’s looking in that pattern on the back. It’s feeling everybody. It’s, you know, I’m showing you. Literally, when you feel their lymph nodes, you guys have your plan for your lymph node exam. My lymph node exam happens and then I like rub down their arm and make sure you tell them why because otherwise it’s very awkward and weird. But it’s a clinical visual inspection and palpation to look for these nodules that they may not know, especially on the back in that Christmas tree pattern. I don’t know how many times a patient comes in and they think they’ve relapsed with their one spot that they can see. And then I look at their back and it is covered in subtle, palpable subcutaneous nodules and Langer’s lines. So that’s really where the dermatologist can come into play. And again, I just tell our team to make sure they’re scheduled with our team regularly. And we will help you before and after because it is a burden and a bit of an expertise and you guys have to keep all of the other organs in check.

Marlise Luskin:

Your organ is the biggest though, right, Nicole?

Nicole LeBoeuf:

Yeah, it is. But honestly, this is truly a situation where teamwork is the best path forward because, you know, I’m like, I think I feel a spleen and the counts are plummeting. There’s nothing on the skin yet, but it’s coming kind of thing and vice versa. So I think that’s where we work together best.

Marlise Luskin:

You know, and I think we could talk for hours about presentation and biology. And, you know, I’m sure there’s things that I’ll have regretted not highlighting here. You know, certainly, you know, our group, we’re proud of the work our group has done, though we certainly have colleagues around the world who have also made discoveries. Go look at the literature, message any of us, and we’ll direct you. But I think I’d love to sort of end on this sort of concept of collaboration. You know, I think you can take that in multiple ways. I think even at a place like ours, which is a relatively large oncology center, and we have a BPDCN interest and focus, we get to work together as a local team—the hematologist-oncologists, our researchers, our dermatologists, our pathologists—and not here on this call today, but certainly our unsung heroes are the folks we work with in the clinical space, our physician assistants and nurse practitioners, who help us take care of the patients. These treatments are so complex, getting people through all the testing they need, getting them their medication, some of the oral medications require approval, how to take it, all the supportive care of the treatments. This is, you know, our nurses, our nurse navigators, our NPs and PAs, you know, they make us look good. You know, we get to come up here and talk about cool things. And we think, you know, we’re delighted to have this invitation, but we couldn’t do it without all of them. So that’s really important, particularly because a lot of these patients, because of the rarity of the disease, are coming from far away. Often they’re relocating or driving long distances to access our expertise. And that adds an additional burden for patients. They’re often in an unfamiliar environment. Driving into Boston, it’s like going to the moon for some people—and for those of us who live there. But, you know, this is really an area where patients benefit from that. And then the collaboration with our colleagues in other hematology/oncology centers. You know, we collaborate. You know, sometimes a patient will come to see us and we give it as much expertise as we can. But they just say, you know, I have to get treated closer to home. You know, we collaborate with those oncologists to sort of identify the best way forward. Maybe the patient is able to come every couple of months to have that reassessment and that guidance. So, you know, working with our referring and collaborating physicians to help you with this really rare disease. If you’ve never seen it before, why would you know these things? And we want to make sure that both by our publications and our resources like this one that we help our colleagues, but we also love direct interaction and direct consultations. So I thought I’d highlight that. And Nicole, I don’t know if you want to mention anything there in your clinic as well.

Nicole LeBoeuf:

Yeah, no, just again, I fully acknowledge that we have an access problem to dermatology out there in the world. And so finding your local friend and having them on speed dial for the rare instance of something like this is really important and will continue to work to advocate for that on our end. And I would be completely incapable of everything without my nursing and my nurse practitioner and PA team. So I agree wholeheartedly. It’s a true team effort from the minute the patient calls.

Marlise Luskin:

I think there’s been a lot of patient advocacy as well, and we shouldn’t forget the patients and their families as part of that team. This is a disease that’s really rare, but it’s a little bit more common than was once thought. More recognition. We’re identifying these patients. We are helping them. I think, as I mentioned, some of these improved diagnostics, venetoclax, tagraxofusp, hopefully more treatments in the future, recognizing things like the need to treat the CNS, other trials that are ongoing. We are moving the needle, but we do need everybody’s help. For those of us who went into medicine because they love patients, love helping them, love thinking about ways to make things better, this is truly a labor of love, and it reminds us why we do our job every day. So we really enjoyed the opportunity to talk about this. And I think those are my closing thoughts. And I know everybody in this group welcomes anybody who’s watching this video to reach out to us with any specific questions and help with your patients. So thank you, Nicole and Shai, for joining me and helping me lead the talk.

Thank you.

Marlise Luskin: Research funding to the institution (AbbVie, Novartis); Advisory Boards (Novartis, Pfizer, Kite, Jazz)