 In simple terms, can you explain what hairy cell leukemia is?

 Hairy cell leukemia is a very unique, rare type of leukemia that is a cancer of a specific type of B cell, which is a mature B cell for reasons that we don't always understand. These B cells can acquire mutations that cause them to grow when they're not supposed to be growing and it may be actually be more than one mutation. And so what we find is that the hairy cells start to involve the bone marrow, spleen and possibly other parts of the body, and eventually can cause problems.

The complications of hairy cell leukemia are actually very similar to other types of similar lymphomas. It is important to emphasize that even though it's called a leukemia, it's actually a type of lymphoproliferative disorder. So, it is very important to differentiate exactly what type of lymphoproliferative disorder this is because it makes a huge impact on the type of treatment that is chosen.

Essentially, when we're trying to figure this out, although some patients may have hairy cells circulating in their bloodstream, that's not actually most common. Most of the time, if it's suspected that a person has a type of blood cancer, we do need to perform a bone marrow biopsy. So, we will look at the blood counts but it's very important to look at the bone marrow biopsy and see what's going on in there. And there are specific panels of tests that are run on the bone marrow that look at the appearance of the cells that are infiltrating the bone marrow, and also specific testing for the proteins that are on the surfaces of the cells, because, for hairy cell leukemia, it is a very unique profile of proteins on the outside of the cell that are detected. If a very specific combination of proteins are present it is very likely to be hairy cell leukemia and it helps to rule out other types of lymphoproliferative disorders; for example,splenic marginal zone lymphomas and others that can actually have hairy cell projections.

The way hairy cell leukemia gets its name is when, initially, scientists were looking at these cells under the microscope, they have these hair-like projections that are very unique and distinct but actually other lymphomas and lymphoproliferative disorders may have a similar appearance.

So once you have the information about what type of proteins are on the outside of the cell and also what mutations are present, because the majority if not all of patients with classical hairy cell leukemia will have BRAF V600E mutations. If the mutation is present and the right type of proteins are present, it's usually very clear that the diagnosis is hairy cell leukemia. There is

another type of hairy cell leukemia that is called variant hairy cell leukemia and it is really important to differentiate these two because the treatment is different variant hairy cell leukemia tends to behave more aggressively and you don't want to mix up the two. Variant hairy cell leukemia usually does not have a BRAF V600E mutation and it's also missing some of those proteins on the outside of the cell.

So, most of the time the diagnosis is pretty straightforward. If it turns out that the diagnosis is not straightforward that might be the time for actually a specialty pathologist such as a hematopathologist to review the case.

 What is the rate of hairy cell leukemia diagnoses in the US each year?

 Hairy cell leukemia makes up about 2% of all leukemias so it's pretty rare. There are only about 600 to 800 new cases of hairy cell leukemia diagnosed in the U.S. per year, although I will say, because the survival has improved so much over the past few decades, many more people are living with hairy cell leukemia than there were originally.

 What are the signs and symptoms of hairy cell leukemia?

Historically, most people, when they would present with hairy cell leukemia, would have a serious infection and come to the doctor's office or get admitted to the hospital with a serious infection and then be identified to have usually low blood counts and a large spleen. Those are two hallmarks of the disease. Nowadays, we're finding that people are diagnosed very early in the course of their illness because they go for their annual physical exam and routine blood work and are found to have low blood counts. That kind of starts the investigation as to what's going on. So, some people are diagnosed a little bit earlier in the course of their disease.

The symptoms of hairy cell leukemia may include, obviously, the symptoms of infection; abdominal discomfort; difficulty eating a full meal, which we call early satiety which indicates that the spleen is so large that it's starting to press on the stomach and cause problems;patients may have bleeding from low platelet counts; infections from low neutrophil counts;and also there is a sort of general immunocompromise that comes from a feature of classic hairy cell leukemia, which is low monocyte counts which, nobody really understands why that happens but it does increase the risk of infection. Some patients may just have overwhelming fatigue that takes them to their doctor's office for an evaluation.

 What is the rate of relapsed or refractory disease occurring?

 Unfortunately, we don't have a cure yet for hairy cell leukemia but some people will stay in remission for a very long time, sometimes over 10 years, depending on how good their remission was with their therapy. So, we sort of feel that about 40% of people will eventually relapse but that percent is probably higher in people who were diagnosed when they were very young, so they live longer with the disease and and may have an increased risk of relapsing just because they are living with it for a longer period of time.

 With the disease being on the rare side, why is there an urgent need for more research and more awareness?

Because this is a rare disease, there's a lot that we don't know about it. We don't have a cure for hairy cell leukemia, but we know that it's a highly treatable disease. When when this disease was first identified many years ago, there was not effective therapy and the average survival was about only four or five years. Since a few key clinical trials were performed, the average survival is now identical to unaffected persons. So people with hairy cell leukemia can have the same survival as if they did not have hairy cell leukemia. So that shows the impact of therapeutic clinical trials that can identify new treatments that can really have an impact on the natural history of the disease.

 What is the key thing patients with HCL should know about their disease?

 They should know that it is a serious illness. Many times, early on in their disease, they get diagnosed with hairy cell leukemia and people know that the outcomes with treatments now, in some cases, are very good. And so they get told that they have a “good leukemia” but from my perspective there is no good leukemia, especially when it's something that you'll be living with the rest of your life and can have plenty of complications, not just from treatment but from the disease itself. So I think it's important to find a doctor that you're comfortable with, somebody with some expertise in the disease to inform yourself about your disease and what are the important things.

I think understanding your own blood counts is very important and knowing how to interpret where you're at with your disease and what is your risk of complications because if you're someone that has a low neutrophil count from your treatment or just from the disease, you really need to go to the hospital. If you get a fever and there's certain key elements, that can be really critical for successful outcomes in hairy cell leukemia.

Organizations like the Hairy Cell Leukemia Foundation that can provide answers and connect with somebody that can help manage problems or side effects and also connect with other patients that can be sort of like peer mentors to help them through their disease and kind of give them some pointers on managing side effects and things like that can be very helpful, especially in a rare disease where you may never meet somebody else with it and outside of an organization that can bring you together. It can be a very isolating experience.

The Basics of Hairy Cell Leukemia

 What types of tests are conducted to determine an HCL diagnosis?

So, there are actuallyguidelines for this nowthat were published in 2016in combination with the Hairy CellLeukemia Foundation. Unfortunately almost all patients willneed a bone marrow biopsyat the time of their diagnosis. 

here's really not another way to getthe necessary information without doinga bone marrow biopsy.

In addition to that, it can be veryimportantto know the size of the spleen

This can be determined several differentways. Oneis with an ultrasound, which isa non-invasive way to get spleenmeasurements

but sometimes if we're concerned thatthere might be other involvement such aslymph nodes that are involved or otherparts of the body. We will recommend cat scans of the chest, abdomen and pelvis, and sometimesthe neckbecause it's very important to knowwhere you're starting from when you'repotentially going to be startingtreatment.

Are these tests similar if the disease has relapsed?

 Yes, and a lot of that will depend on symptoms. So, at the initial time of diagnosis, some people may not have any symptoms. For example, enlargement of the lymph nodes or other areas where the disease may be involved, for example, some people develop bone involvement later in the course of their disease that is not present at diagnosis, and so sometimes the investigations that are used depend on symptoms and physical exam findings. So if the doctor is finding enlargement of the lymph nodes on the physical exam they usually will order a cat scan to evaluate that further or if the patient is having symptoms in a specific area, picking the best diagnostic test for that area. So it may be very different, actually, at the time of relapse than it is initially at the time of diagnosis.

 What is minimal residual disease, or MRD, and how does it play a role in hairy cell leukemia?

MRD is disease that is still detectable after the completion of treatment and usually that means that when the pathologist looks under the microscope, they don't see hairy cell leukemia but when they do more specific tests such as specific types of staining or, for example, flow cytometry where you can run the bone marrow or blood through a machine and see if those cells are present. That tells us that the patient has not achieved a complete remission. There are still some cells present.

What we know now in hairy cell leukemia from previous work that's been done by Dr. Kreitmanand others is that when a person still has hairy cell leukemia when they finish treatment, their disease is more likely to come back in a shorter period of time. And so sometimes that can be very important information when you know that somebody has had a complete response and they have no detectable minimal residual disease at the end of treatment, they're likely to stay in remission a really long time.

I think, either way, whether it's present or not, it's very important and helpful information for both the patient and the doctor when you're trying to decide how to follow up when the patient needs to be seen again.

Ultimately, I think there will be clinical trials using agents directed at eradicating minimal residual disease. So that may be an opportunity for clinical trial participation.

 Well I'm happy to say that if we do our job correctly, which is managing things at the time of diagnosis well and making sure that infections are well treated and we've tried to minimize complications, patients with hairy cell leukemia should have a survival similar to if they did not have hairy cell leukemia. So I think that is one of the reasons why we sort of urgently feel that it's important to get hairy cell leukemia patients connected with good information, providers that can help guide therapy especially when an unanticipated complication occurs because we really want people to have that benefit of extended survival that we can see now with modern therapies.

What is the best way for a patient to make sure that they're seeing somebody who is a specialist in this disease?

 So there's not that many people who specialize in hairy cell leukemia, so the easiest way to get connected with one of those providers is to go to the Hairy cell Leukemia Foundation website, which is 

, and there is a list of Centers of Excellence on that website. It lists the providers that are treating hairy cell leukemia at each

Center of Excellence and tells you where they are in the country. Typically at a Center of Excellence, you'll have not only somebody who is doing research in hairy cell leukemia and treating patients but you'll also get the benefit of the expert hematopathology because typically at the Center of Excellence there's also a pathologist specializing in the diagnosis of hairy cell leukemia. So it can be very helpful especially if there's any question about the diagnosis to have an expert in hematopathology review.

Why is it key to make sure we’re optimizing the interaction between a patient and their health care provider?

It is really important because I think that the patient may not always know when they need to be seen. For example, what sometimes are expected symptoms are unexpected. I think it is important to have a very good relationship with that provider and also the team of providers. Usually we have other people that we work with, like nurse practitioners. This is a disease that you need a lot of education around, particularly understanding your own blood counts and when to call with symptoms or side effects. I think just having that comfort level and trust between the patient and providers really improves outcomes because things don't get delayed when there's a problem.

 How can patients become informed about their diagnosis to be their own best advocate?

 Forums like this, watching videos informing yourself. The Hair Cell Leukemia Foundation has a list of available clinical trials and also some results of other clinical trials that have been completed. It also has a frequently asked questions section where people can kind of scroll through and see what questions have been submitted and what the responses were. There are a lot of patient specific organizations such as the Leukemia and Lymphoma society, which will have information both generally about leukemia and also more specifically about hairy cell leukemia, because it is a rare disease that can be harder to find information. Also being very active and checking some of the social networks; I know that there are some groups on Facebook that are hairy cell leukemia patient groups. Getting connected with patient advocacy groups can be really helpful just to get more resources around management of the disease and also to feel more connected to your hairy cell community definitely.

What is the caregiver’s role in a hairy cell leukemia diagnosis?

We know from a lot of different types of hematological malignancies that having a good caregiver is really important for optimizing patient outcomes because there are definitely times when patients don't feel like taking their medications or feel like going to that doctor's appointment or feel like going for a walk. The caregiver can help be there to be the cheerleader and just kind of make sure that things stay on track because it does get having a chronic illness, and that's really what hairy cell leukemia is. It is a chronic illness that this person is going to be living with the rest of their life and so these are things that we don't really think about when it's starting. But years down the line, people can sometimes get tired of dealing with a chronic illness so the caregiver can be there to really make sure that patient is staying on track with what they're supposed to be doing and providing emotional support.

It's very common for people with hairy cell leukemia to receive messages that this is a “good” leukemia and I think that that causes patients sometimes to not want to complain or make too much of it. So, the caregiver can help to reiterate that this is and can be a serious problem that needs to be taken care of. You don't want to minimize it, even though it's very treatable. Not paying attention to it could cause a big problem.

 What is your biggest piece of advice for a newly diagnosed patient?

 My biggest piece of advice would be to find either somebody with a lot of expertise in the disease to help take care of you or to connect an expert with your own doctor. Most of us in the hairy cell leukemia community are happy to talk with other doctors just to help, especially if there are difficult questions or problems with treatment decisions to help those providers to optimize the care and for the patients to not be afraid to reach out and get additional help because some very busy oncologists may have only seen one or two cases of hairy cell leukemia in their career. A lot has changed in the treatment landscape and there are also a lot of pitfalls when you start treatment. For example, watching out for infections. So either finding an expert to take care of you or helping your own doctor to connect with an expert to discuss things early on is probably one of the most helpful things that you can do to get the best care that you can.

Seeking a Hairy Cell Leukemia Specialist

Why is it important for patients to consider joining a clinical trial?

you're generally being treated byexperts inin the disease because when you do a clinical trial, particularly in hairy cell leukemia, you need several more than one or two patients. As many patients know, their doctor might tell them that they've had very few patients they've treated with hairy cell leukemia. But when you do a clinical trial you're treated by someone who sees lots of patients with hairy cell leukemia. That’s really important. You get better care when you're on a clinical trial. You're also given access to drugs that are sometimes not accessible to patients who are not on a clinical trial. That’s important as well. You get more follow-up. You might have to get your blood drawn more, you might have to go to the clinic more and nowadays fortunately they're having telemedicine. You have more clinic visits in clinical trials but most patients that have clinical trials are very happy that they that they did them. And now we have clinical trials in all different lines of treatment, both in newly diagnosed and relapsed hairy cell leukemia. Patients should be encouraged to take advantage.

One of the newly diagnosed hairy cell clinical trials that is now available is (Gazyva [obinutuzumab])- (Zelboraf [vemurafenib]) trial for newly diagnosed hairy cell leukemia. That’s being run out of Memorial Sloan Kettering Cancer Center in New York. That is one trial that is currently active. But there's many trials for patients in the second- and third-line setting.

 How can patients learn more about clinical trials they may be eligible for?

 A good way is the Hairy Cell Leukemia Foundation website, hairycellleukemia.org. The website has a part for patients with a list of clinical trials that are currently open. It’s a good way to find out who's doing them, get some links to getting more information. Also, not only our team, but other teams are very happy to take questions from patients to find out more about the clinical trials. Patients can speak with their doctors as well

 Are there certain questions that patients should ask their physicians?

It’s important to find out about the clinical trial and what the expected results are, how much participation is needed, how often they need to leave town to go get treated or get follow up, how long the clinical trial is, what expenses might be incurred by them. I think most patients are pleasantly surprised to find out that it's a very good opportunity, but it's certainly something that patients need to be informed about and certainly making sure that they're eligible for the trial.

One of the things that our group does a lot is to have blood and medical records sent in ahead of time. That way there's no surprises. Patients won't come and then find out at the last minute that they don't really have hairy cell or they have some other variant, if they’re going to be treated with a BRAF inhibitor. We make sure that they have the BRAF mutation ahead of time to make sure that they're eligible.

Can you discuss how MRD is being evaluated in trials right now?

 It's something that's changing fromyear to year. Back in the late 1990s, when minimal residual disease was first being considered, it was cells in the bone marrow biopsy that you could detect by what's called immunohistochemistry, by special antibody stains you could tell that there was collections of hairy cells in the bone marrow biopsy. And then we had more sensitive tests for MRD. You can do flow cytometry, which is where you have a liquid and you have a laser going into that liquid when you shoot it through a tiny capillary tube and you can tell certain antibodies, antigens and markers on these hairy cells. You can really define very accurately what type of disease it is and what type of markers the hairy cells have. It’s a very accurate and very sensitive test of minimal residual. Flow cytometry is most sensitive. There is also a test called polymerase chain reaction (PCR) where we can detect minimal residual disease. These tests are not quite as accurate and sensitive. That's being done in in many trials. Or you can do PCR looking for what's called immunoglobulin rearrangements, and that's being done in in other trials.

There’s a wide variety of different ways that you can detect MRD and I would say that the most common is still the old method, which is immunohistochemistry of the solid part of the bone marrow where we can detect minimal residual disease. One of the nice things about that approach is that it can be done in retrospect. If you have a patient who had a bone marrow years ago, you can go back to that bone marrow which is preserved in wax and you can make new unstained slides and you can stain those slides and you can look at the immunohistochemistry to check for minimal residual disease. So it's a popular method to test MRD in clinical trials.

 What are some clinical trials in progress that patients can consider?

 There’s several clinical trials. I mentioned the one in New York. That’s an interesting trial for first-line treatment of hairy cell because it doesn't use chemotherapy; it's a chemo-free first-line regimen which should get rid of minimal residual disease. So that's quite exciting.

There are small trials of the BRAF inhibitors. At the NIH, we’re starting the vemurafenib and dabrafenib combination. There is also the combination of (Braftovi [encorafenib] and (Mektovi [binimetinib]), which may have some differences in side effects and may have some advantages.

We have a trial that's open using binimetinib alone, targeting MEK. We’re combining (Rituxan [rituximab]) with a purine analog.

There are several trials open in the second-line treatment of hairy cell, where patients are getting a combination of cladribine plus rituximab, where the rituximab is either being given early up front on the first day of the cladribine or the rituximab is delayed at least six months later. That trial has a very high complete remission rate and a very high rate of elimination of minimal residual disease and it's used in second line.

Then there's a trial in the third-line meaning after several relapses using either bendamustine and rituximab or pentostatin and rituximab. These trials also have a very high rate of complete remission without MRD, but these trials with chemotherapy plus rituximab have toxicities. One of our favorite trials is the (Lumoxiti [moxetumomab pasudotox]) plus rituximab trial, and that's a chemo free treatment where the moxetumomab pasudotox has a capacity of causing complete remission without MRD. We’re adding the rituximab in order to increase the rate by which patients can achieve complete remission without MRD.

There’s also other trials being done with (Cotellic [cobimetinib]) and vemurafenib and rituximab.

We can look forward to other clinical trials being open in the future.

 What is your biggest piece of advice for a patient considering joining a clinical trial?

 Don’t rush into treatment. In general, hairy cell is an indolent disease. Sometimes the counts can drop. It can look like a pretty big drop. It can scare patients and they might say I've got to get right away. But then they get another blood count and it doesn't look as bad. So, I would encourage patients to take their time. If their doctor says we need to treat this tomorrow, I would say not so fast. Let’s really think about what we're doing, especially if you're going to be starting another chemotherapy drug which causes long-term cumulative toxicity. Think about some of the other options that may be less toxic, maybe more effective actually. That would be my major advice to patients, to take their time and really consider the many options that we're very fortunate to have these days.

Joining a Hairy Cell Leukemia Clinical Trial

When a patient gets diagnosed with hairy cell leukemia for the first time but doesn't need to be treated, that's called watch-and-wait. You just watch and you wait until the counts get bad enough or the spleen maybe gets big enough that causes symptoms and there's an indication for treatment. It’s rare – less then 10%, probably 5% of patients can escape treatment for their whole lives. It’s not quite as common as some other chronic diseases where you can avoid ever being treated but, in general, we don't jump into treatment until there are indications for treatment.

Generally, the normal blood counts have to be low, at least one of them, or the spleen has to be enlarged and painful. There are some other indications for treatment that can be used but those are the main ones.

Can you discuss other standards of care for treatment?

The most popular first-line treatment for hairy cell leukemia is single agent cladribine, and an equally good first-line treatment is pentostatin – these are purine analog chemotherapy drugs. They do have toxicities, but they're remarkably well tolerated. They can cause a range of different side effects: stem cell damage, neuropathies, nerve damage, normal blood counts to go down even lower than they were to begin with and that can cause fevers. Generally speaking, if patients start out with very low neutrophil counts the neutrophil count can go down very low with treatment. With either of these treatments, cladribine or pentostatin, patients have to be very careful to let their doctors know or come into the emergency room if they have fever because that means low neutrophil count and that means their infection-fighting ability is very low and it could there could be serious consequences if you don't get antibiotics. So that tends to be more common in patients who present with low neutrophil counts, but we see even patients with normal neutrophil counts when they start, can go down very low with even the first treatment with cladribine or pentostatin. So you have to careful about that. Pentostatin is given every other week for three months, up to six months sometimes. That’s a little bit more gradual, a more gentle treatment. Cladribine is generally given once a day for five doses or continuously for seven days. So it's a little bit more treatment packed into the first week and so we may see more side effects in terms of the bone marrow suppression, the low blood counts during that or just after that time, and it can take a month or more for the normal blood counts to come up.

What is the standard of care in the relapsed/refractory setting?

 Patients are being treated with the same treatment as first-line treatment, however, they can combine it with (Rituxan [rituximab]), which is a CD20 monoclonal antibody that binds to CD20 and it gets the cells to commit suicide or get the immune system to kill the hairy cells and it works very well with the chemotherapy. It has some synergy, that means that two things that are used to treat work together to produce a very good response. We know that happens because rituximab makes the cells more sensitive to the chemotherapy. So, general speaking, if patients have had more than a two-year complete remission to the first-line treatment then one is more likely to be able to get away with the first-line treatment that they had before or maybe the alternative. In other words,if they started with cladribine they could get pentostatin the second time or vice versa. If, generally speaking, they got less than a two-year remission or they got a partial response, which means they didn't get a complete remission at all, then you'd be more likely to combine the purine analog treatment with rituximab.

I should say that there is new information from a randomized trial that if you give the cladribine

and rituximab together in first-line treatment then the results are extremely good. Not only do you have a higher complete remission rate but you eliminate minimal residual disease (MRD). Minimal residual disease is traces of hairy cells that are left behind by chemotherapy and they cause relapse over time, and given enough time they will grow into a relapse and patients will have to get treated again. So, if we can get rid of the MRD, then we can potentially prevent patients from relapsing.

So there is some new information that if you treat with cladribine and rituximab together early on for first-line treatment, you can eliminate the minimal residual disease. Over many years, median or average time of follow-up, around six-and-a-half years, very few if any of these patients need more treatment or they have no minimal residual disease. Their counts are excellent and if you compare that to a group of patients that were treated a long time ago with cladribine and then you wait for many years to relapse, about 28% of patients will relapse over about six years or so. This is being used more and more, but it’s not part of the official guidelines because the official guidelines in 2020 came out before the randomized trial was reported. But it's something that people are using more and more.

A group at MD Anderson, previous to that trial, studied cladribine followed a month later by rituximab, and also found a 100% complete response rate and also a good removal of minimal residual disease. There is some controversy now about whether this should be part of the first-line treatment of hairy cell leukemia.

Now, I want to back up and say that after that, if patients have a very poor response to their first course of cladribine, there is a drug called a BRAF inhibitor that could be used in the second-line and that's called (Zelboraf [vemurafenib]) and that's recognized as a legitimate second-line treatment, or in other words after the first relapse, that can be used providing the complete response to the first-line chemotherapy was less than two years or if patients had no complete remission. But in order to use this drug, you have to demonstrate that you have the BRAF V600E mutation…This mutation was discovered by a group in Italy in 2011 in hairy cell leukemia. It was shown in a trial in 2015 to be very effective in relapsed hairy cell leukemia. This is a recognized treatment in the second-line and it's certainly one of the treatments that is recognized in the third-line and beyond, that means relapsed several times. Vemurafenib has been combined with rituximab and it has much better complete remission rate. It eliminates the minimal residual disease as well, so about two-thirds of the patients have no evidence of minimal residual disease. But we don't have long-term data on it.

The other treatment that was just approved in 2018 for relapsed hairy cell leukemia is a drug called (Lumoxiti [moxetumomab pasudotox]). This is a drug that is very different than chemotherapy. It is made out of an antibody that binds to CD22, which is on the surface of hairy cells. It goes inside and then the toxin kills the cell and this drug is quite unusual in that it can eliminate minimal residual disease and cause complete remission as a single agent, and it's not chemotherapy. It doesn't cause chemotherapy toxicities. The problem with this drug is that you have to be careful when giving it. It kills cells that it gets inside so it pokes holes in the blood vessels and it makes the blood vessels leaky so patients have to drink lots of water when they're taking it…It’s very well tolerated. If you don't hydrate well that drug could cause some kidney damage and so you have to be very careful.

There’s another recommended drug in the third-line and beyond, (Imbruvica [ibrutinib]). Ibrutinib is a great drug. It's approved for chronic lymphocytic leukemia and mantle cell lymphoma and some other hematologic tumors. But in hairy cell leukemia, it works very slowly but surely. We’re waiting for a full report of a clinical trial. It has some excellent effects and one of the advantages of this drug is that it you don't need the BRAF mutation and sometimes it's very helpful even in patients who don't have the BRAF mutation.

…Lumoxiti is a drug which was specifically approved for hairy cell leukemia. There are insurance companies that will pay for ibrutinib and rituximab, but generally speaking these drugs were not approved for hairy cell leukemia. Whereas lumoxiti is a drug that works especially for hairy cell leukemia, so it is approved for hairy cell leukemia.

 What do patients with hairy cell leukemia have to look forward to?

 There's so many more treatments now. They can look forward to having treatments that work very well – not only that work but can be given orally for those patients who want to avoid getting IV treatments. Intravenous treatments allows patients to get out and avoid having to go back to the doctor. We find that the oral treatments by themselves tend to spare the minimal residual disease. The patients will continue to have minimal residual disease which means that if you stop the oral drugs, the disease will come back. Although sometimes it takes more than a year for the for the disease to come back. If a patient really wants to have a treatment that makes it so the patient will not need any treatment in the future and, therefore, not have any side effects from treatment, then you really need a treatment that can eliminate the minimal residual disease.

Those treatments include moxetumomab pasudotox as a single agent and vemurafenib plus rituximab can do that. Although we don't have long-term data on that combination. One thing we do have long-term data on is the cladribine plus rituximab given in the first-line, but we also have data on other purine analogs like pentostatin…that can give very high complete remission rates without minimal residual disease. There is a lot more that we know now that has not been published and will be published soon. Those kinds of combinations with the rituximab generally offer the possibility of elimination of minimal residual disease. Many patients are happy not having the minimal residual disease eliminated but being able to be treated chronically with treatments that they can tolerate, providing they can tolerate them well, including the ibrutinib and the BRAF and MEK inhibitors.

Expanding the Horizon for Hairy Cell Leukemia

New content coming soon, please check back later.