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Hairy Cell Leukemia Patient Forum

November 13, 2019

La Jolla, CA

Hosted by the Hairy Cell Leukemia Foundation with guest speaker Dr. Alan Saven, Scripps Clinic, La Jolla, CA

Transcript

The following is a transcript of the Presentation given by Dr. Saven followed by a Question and Answer session with the audience.

Presentation

Alan Saven: These are the typical features of hairy cell leukemia: the hair-like projections, and if you look at the nucleus, there is a lot of cytoplasm, which is the material surrounding the nucleus.

Hairy cell leukemia is a malignancy of B-cells and there are certain proteins that are expressed on the surface of hairy cells. These markers are 19, 20, 22, 11C, 25 or one of the 3. There are certain diseases that can mimic hairy cell leukemia and look very close to it. One is called marginal zone lymphoma.

Before there was flow cytometry there was something called the TRAP stain, but it is no longer really used because it is not specific for hairy cell leukemia. The bone marrow aspirate of hairy cell leukemia is said to have a fried egg appearance, because the nuclei have a rim around it, like the yolk of an egg and the white part. So it is called a fried egg appearance and it is pathognomonic of this illness, with or without the flow cytometry.

Often you can get the juice out of the bone marrow, because there is a lot of fibrosis that is often the scarred marrow.

Not every patient with hairy cell leukemia has the BRAF mutation. It is probably 80 or 90 percent of patients who express this mutation that drives the malignancy. It has diagnostic and therapeutic implications. One of you had mentioned that your father was on Vemurafenib; you would only use Vemurafenib on people who had the [BRAF] mutation, but most patients have that mutation.

You do not treat everybody with hairy cell leukemia; you generally treat people who have significant lowering of their blood count. So if you just did a bone marrow and found hairy cell, but the blood counts are good, there is no advantage to treating the patient.

No therapy in 2019 is curative. That means that like hyper-tension or diabetes, these are disorders that need to be managed, so you only have to manage it, if and when there is a problem associated with it. Generally people get treated if the neutrophil count is below 1,000 or a hemoglobin below 10 or platelets below 100,000.

If someone has a platelet count of 90,000 that has not changed over 10 years, I would not treat the patient. Generally, when your neutrophil count goes down, you are at risk of infection, if your hemoglobins are below 10, you get to be fatigued and if your platelet count is less than 100,000, then there is the risk of it going further down and the risk of bleeding. People do not really bleed until they hit below 20,000.

Much more rarely, and you would begin to question the diagnosis, is if the white count is very elevated. There are some variants of this disease in which the white count goes up, not down. Rarely, people can have a spleen the size of a pregnant woman and that can be very symptomatic. There are rare patients who have big lymph nodes in their neck and require therapy.

If you don't meet those kind of criteria, then the patient can just be observed and there is no detriment to the patient; they are not getting short-changed, no treatment has no side effect. So if the patient, either at first presentation or at relapse, has good blood count, I’d be inclined to observe him.

Alan Saven: There are 3 drugs approved to treat hairy cell leukemia as front-line treatment. These drugs are approved to treat refractory disease, but there are 3 drugs approved to treat hairy cell leukemia. You have probably all heard of Interferon. The disease that got it approved was actually hairy cell leukemia. It became a billion dollar drug to treat hepatitis, not hairy cell leukemia, but it's first approval was hairy cell leukemia.

Cladribine's first cousin is Pentostatin; they are similar but not identical drugs. Pentostatin is also known as deoxycoformycin. Then there is Cladribine. We do not use Interferon much to treat hairy cell leukemia anymore, because it does not have any ability to clear the bone marrow out. Most of the remissions [with Interferon] are partial, rather than complete, and people don't like self-injecting a medication for up to a year.

Pentostatin is given every other week, for 3 to 6 months of therapy. Pentostatin has a high complete remission rate. That means that if you look under the microscope, you won't see hairy cells. But, if you do special stains, in about 3 quarters of those complete remissions, you will see hairy cells. No one thinks that Pentostatin can actually cure hairy cell leukemia, but it does have a high overall response rate. It's a good drug; the spleen goes away, the bone marrow normalizes under light necropsy, and they have normal blood counts. It does take many months of therapy.

Initially we gave everybody a continuous infusion of Cladribine for seven days, because the in vitro studies said that you needed continuous exposure. Ultimately we tested various other ways to give the drug. This way has become the most popular now and it is the way I do it presently. We give it as a 2 hour infusion for 5 days. In diseases other than hairy cell leukemia, where people used to use Cladribine, they used to give it every 28 days, but for hairy cell leukemia you just need one cycle of drug. The results for the 5 day, 2 hour infusion were almost identical to the 7 day continuous infusion. I do not use it as a continuous infusion anymore. You can give the drug orally and you can even give it subcutaneously. It is approved in Europe to give it subcutaneously. This is not the way I have done it.

Everybody used to come to San Diego for the disease so we accumulated a large number of patients. Over the years, I probably treated 800 patients. You can see the complete remission rate is very high, 87 percent, with about a 10 percent impartial response rate. There are very rare patients who do not respond to cladribine. It’s not 100 percent, but it’s very impressive. Hairy cell leukemia was really changed by the advent of these kinds of drugs.

The responses are usually very durable, and it is better to clean out the bone marrow than not to clean out the bone marrow. So complete remitters do better than people who get partial remission. I had mentioned before, if you do special stains on the bone marrow, you can see that about a half to two-thirds of patients still have disease in their bone marrow. One of the mistakes that people make, who do not see a lot of this disease, is that the drug can work for up to a year after you stop the drug. If you do a bone marrow at 3 months, you can see the disease, but if you do a bone marrow at 6 months, you might not see it. Similarly at 6 months, you might not see it at 9 months and at 9 months you may not see it at 12 months.

Why the drug takes so long to work, is not well known, but hairy cell leukemia is a very slow growing form of leukemia. The mistake is to start making therapeutic interventions at 2 months or 3 months or even 4 months, because things will actually better over time. There is a popular program where they give you the 5 days of cladribine, at week 4 they do a bone marrow and if you have hairy cell leukemia they give you 8 doses of Rituxan. They show spectacular results. But, at 4 weeks it is very early after Cladribine, so if they did that bone marrow at 6 months, it might have been gone already. This has become a popular way to treat the disease.

The survival of hairy cell leukemia is almost that of a normal population. I put a paper out on it a couple of years ago looking at younger patients for this disease; with younger patients it tends to be a little more aggressive, but it is very similar to that of the general population. Especially now because there are more and more therapies.

Most people use Cladribine as frontline therapy. It was developed in the mid 80's and it has remained as the frontline therapy ever since. There are other ways to treat the disease now as well.

Up to 40 percent of patients who get the drug get a fever. We found very few infections in the patients. In the illness, we break the hairy cells up, that generates substances that cause fever. We spent a lot of time admitting patients for what's called neutropenic fever. That counts as a fever, but actually we got very few infections. Someone told us they got 10 shots of the filgrastim which is Neupogen. We did a study many years ago, where the Neupogen has very little or no benefit to the patients. It elevates the white count, but if you look at the clinical parameters of number of infections, number of patients admitted, number of antibiotic days, it actually doesn't do very much. Usually people use Neupogen for documented infections, to try to temporarily improve the white blood count, so that you can overcome infections. But, it is common to see a low white count after cladribine and it takes probably 4 to 6 weeks to normalize the count. In some patients, it can be very protracted months before the counts normalize. I don't regularly use the Neupogen; I use it in those patients who have documented infection.

So that is how we treat frontline people with hairy cell leukemia.

What about a patient who relapses after cladribine treatment? Men get hairy cell leukemia much more commonly than women, but women certainly get it. I don't know why. This is a 67 year old man. He had a big spleen and a very low blood count. We did a bone marrow, we did that thing called flow cytometry and we confirmed that he had hairy cell leukemia. At that time he had been given Cladribine previously. He had received it 2 years previously. So he relapses, his blood counts are bad again, we re-prove it and he has hairy cell leukemia. So what are his options now, because he has had Cladribine and Heparin? You can try Cladribine again. We don't generally recommend it if the first remission wasn't more than 2 years, because if it didn't work so great the first time, chances are it's not going to work so great the second time. There are only so many courses of Cladribine you can give, before you begin to damage normal marrow elements.

This slide looks at 207 patients, the upfront treatment. We had a 95 percent complete remission rate, then they relapse, got more Cladribine, relapsed, got more Cladribine, relapsed and got more Cladribine. Over time, the complete remission rate decreases and the durability of the response decreases over time. But if the person had the drug today and relapsed 10 years from now, I would probably give it again because it has been 10 years. But if the patient relapsed at 18 months, I would probably try something different. So you can use the same drug again depending on the durability of the response.

Same history of Pentostatin; you can treat again with Pentostatin. There isn't that much data available, only small numbers of patients. If you give the Pentostatin again, the remission rate generally falls, as does the durability. Cladribine and Pentostatin are not identical drugs, they are similar drugs. I published on some patients who had received the Pentostatin before and then the Cladribine, and you can see that some people will respond to Cladribine but don't respond to Pentostatin.

The newer way to treat hairy cell leukemia: There is what's called a monoclonal antibody, so it's a protein directed at the surface of the hairy cell. Rituxan is the most ubiquitous monoclonal antibody. They sell 8 billion dollars a year of Rituxan, not to treat hairy cell leukemia, because it is used to treat lymphomas and things such as neurologic disorders and all sorts of disorders.

It is an immunosuppressant drug. It has activity in hairy cell leukemia, because hairy cell leukemia expresses CD20. Hairy cell leukemia also expresses CD22, and some of you have received Lumoxiti (moxetumomab), which is a monoclonal antibody against CD20 with a pseudomonas toxin attached to it. We will get into the side effects of that later.

Because most hairy cell patients express the BRAF mutation, there is a BRAF inhibitor called Vemurafenib that was developed to treat malignant melanoma, which luckily you don't have. But they both have the same mutation, so Vemurafenib is often used to treat hairy cell leukemia. It isn't FDA approved for this indication.

In California there is a law, if you can show 2 journal articles with peer review, they have to approve it. So I haven't had any difficulty in getting Vemurafenib for refractory patients. I've never used it frontline and I don't plan on using it presently.

Vemurafenib inhibits this mutation and sometimes you use Vemurafenib with other drugs in combination, like in malignant melanoma, because some of the hairy cells will bypass the narrowing and you have to use, what is called MEK inhibitors as well. Sometimes 2 drugs are better than 1.

I have a young man in his early 30s and he's been getting Vemurafenib and Trametinib because he didn't respond very well to the Vemurafenib and when I added the second drug, it actually cleared his bone marrow. There aren't many publications using Vemurafenib in combination with other drugs. Some people combine it with Rituxan.

Alan Saven: Rituxan is often used, either alone or in combination with other drugs. Hairy cell leukemia has bright expression of it. If you stain the bone marrow of patients you can see that hairy cells have bright expression of CD20. A long time ago, we published some patients with using single agent Rituxan; we didn't get very spectacular results. In Texas, they used 8 doses, whereas we used 4 and they got much better results. It is a reasonable way to treat people, because it is very well tolerated and it's not really chemotherapy. It’s a monoclonal antibody protein. It has some single agent activity and some people have used it to try eradicate what's called Minimal Residual Disease.

There are some physicians who think that's important in hairy cell leukemia and there are some people who remain on the fence. So whether it's important to clean up the bone marrow or not, remains to be seen. Some people have non-randomized data, saying they can have very long lasting remissions if you get MRD negativity.

I don't know what MRD means in this particular disease. The more aggressive lymphoma, it means a lot, in acute leukemia, it means a lot. I think MRD is a research tool. I haven't generally treated people for MRD negativity.

There are publications that come from M.D. Anderson in which they give the 5 days of cladribine and then at week 4, they give the 8 doses of Rituxan and they get spectacular results. You get spectacular results from cladribine alone. Kreitman has a study in which he gives the 5 days of cladribine and then on day 1 of the cladribine you begin the Rituxan instead of waiting the 4 weeks. You get 8 doses of the Rituxan and then again you get spectacular results. I think some of you around the table have read his publications and you want to get it. What the Rituxan adds to the cladribine, I am not quite so sure. His results are very good. So I am willing to do it, because there's peer reviews leverage.

Lumoxiti - this was the publication in the New England Journal of Medicine, in which they did lipid anti-CD22 antibody and then attached the pseudomonas toxin to it. The antibody attaches to the cell, it gets internalized, then breaks open the cell. An international study looking at heavily pre-treated patients got the drug approved; it was the study that Dr. Kreitman headed.

Their primary endpoint was that these people could normalize their counts for 6 months or greater. They found that in about 30 percent of patients, you could get durable normalization of counts. Overall if you take all the various patients, you get a 75 percent response rate. Lumoxiti is a very important addition to the therapeutic options for patients with hairy cell leukemia. It has some side effects that are unique to it. First of all you have to drink a lot of water, which for some patients is hard work. I think it's 1 glass of water per hour for the first 8 to 10 days.

Then it can also cause what is called Hemolytic Uremic Syndrome. It's rare, but can occur and then there’s Capillary Leak Syndrome, escaping of water through the capillaries. Results [with Lumoxiti] are very good, because this was a very refractory group of patients with hairy cell leukemia. I think to enter this study you had to have received cladribine before, so the response rate with Lumoxiti was very good.

Vemurafenib is a very important addition to the arsenal for hairy cell patients. It is a very novel way to treat this disease; you have to have the [BRAF] mutation. For elderly folks, despite the reduction in the dose, it's still a difficult drug, you can get a lot of skin reactions, skin cancers, loss of appetite. For those patients who received other drugs, it’s oral therapy, outpatient therapy and a very important therapeutic advance for refractory and relapsed patients.

As I said before, when you inhibit, you only inhibit one mutation, if there's other mutations, then hairy cells can escape, so maybe in the future people will use other drugs in combination with Vemurafenib, a drug to combat that sort of resistance.

Alan Saven: People have combined various modalities. Some people believe you should add Rituxan to the Vemurafenib, like you can do it with Cladribine. Some people have used the drug that's very popular to treat low grade lymphoma which is called Bendamustine, with or without Rituxan. Then at the recent meeting in Rome, there is some data saying that Ibrutinib may have a role in treating patients with refractory disease. I'm not sure necessarily the insurance company is going to pay for this drug for hairy cell leukemia, but it is something that you can try. I don't know if it will ever be approved to treat hairy cell leukemia.

There's more to hairy cell leukemia than just low blood counts. People can get weird infections. I saw a patient recently who had been seen at the university. He had cryptococcus, he presented with headache, they found his blood counts were low, did the bone marrow and they found that he had hairy cell leukemia. When someone is actively infected, you don't want to use Cladribine, you don't want to use Pentostatin, you want to treat the infection and actually Vemurafenib would be a very good way to treat this disease in someone actively infected. He got Vemurafenib. Vemurafenib doesn't always clean out the bone marrow, but at the end of his 6 months of treatment he still had hairy cells and then I gave him the Cladribine. His cryptococcus had been well treated.

There are a number of patients who have picked up weird infections and it's not just about the low neutrophil count, there's more to the immunocompromised with hairy cell leukemia than just the neutrophil count.

You could get a whole lecture just on how you treat actively infected patients. Neupogen can be used to bring up the white count if Vemurafenib doesn’t cause neurological impairment. Interferon used to be the treatment of choice, historically people would have their spleens taken out. And for those people who have had their spleens taken out, they may go decades before their hairy cell leukemia needs to be treated. But the drug to avoid to avoid is the Cladribine and Pentostatin because they are very immunocompromising.

One of the questions has always been, do patients with hairy cell leukemia live for very long periods of time? Do they get second malignancies? They do get second malignancies, higher than the general population, but that risk is still very small. You can see it with Cladribine, you can see it with Pentostatin and you can even see it with Interferon. The risk is still very small. There's not much you can do to prevent the second malignancies, obviously you should get your colonoscopies when you're supposed to, make sure you get a dermatological exam annually and you shouldn’t smoke. But you shouldn't be smoking anyway.

It's probably more related to the disease, because patients with CLL also have increased second malignancies, but patients with hairy cell leukemia do as well.

I will be happy to answer any questions that I haven't answered already.

Question and answer

Audience member: I got confused about the BRAF mutation, is it too late to try and find out what my BRAF mutation is?

Alan Saven: No, I think you can do it on archival material. You could go back to the hematologist and say, “you know that bone marrow I had? Then do some of that BRAF stain with it.” But if you are doing well and you don't need any treatment, it's sort of academic. Ask for the BRAF mutation stain, because if you're positive it opens up a therapeutic opportunity.

Audience member: Okay so, my BRAF is negative.

Alan Saven: The fact that you're BRAF negative doesn't mean you haven't got hairy cell leukemia. But I wouldn't try these kinds of drugs.

I should also tell you that some people get the stain done on the outside and then I request the blots and I do the stain here and it's positive. Sometimes you have to do it more than once, because you might miss it.

Audience member: [My doctor] asked for PCR, he did a PCR, it was negative.

Alan Saven: PCR is just a way of amplifying DNA. Maybe you're BRAF negative, but I'm not sure we know the prognostics and the figures of that.

The fact that you are BRAF negative, if you truly are negative, would mean that there's no point in giving you Vemurafenib.

Audience member: What is the wait and watch?

Alan Saven: The thing is, when you initiate therapy, you wait for the neutrophil count to get below 1,000 or hemoglobin's below 10 or platelets below 100,000.

Audience member: I get colds a lot.

Alan Saven: Everybody gets coughs and colds. We are talking about pneumonia, unusual infections. If you have a cough or a cold, I would recheck [platelets] in a couple of months and if it’s still down, then a decision needs to be made.

We used a hundred as the entry point. But, if someone was stable at 80,000 and it had been stable for 10 years, then I probably wouldn't initiate therapy. But if you were newly diagnosed with 80,000, then I would be inclined to do a bone marrow to prove it is hairy cell leukemia and then give you a therapeutic recommendation.

Audience member: Curious if a fungal infection in the armpit is a common thing?

Alan Saven: Well it's common in everyone to get an infection in your armpits. I don't think it's a hairy cell manifestation.

Audience member: How about hair growth. Have you heard anything about hair growth?

Alan Saven: No HCL doesn't cause hair growth. Not so lucky.

Audience member: Do you see any future with gene editing like CRISPR?

Alan Saven: Those technologies will work when there is more homogeneity of an illness. There are certain diseases in which you know what the genetic abnormality is and you can try to correct it. For example there is a disease called CML, chronic myeloid leukemia, in which all the patients have the same mutation, called the Philadelphia chromosome. There are ways of trying to edit what is a single mutation. When people have done genetic analyses of hairy cell leukemia, there is great heterogeneity. That would be less applicable to try to correct the DNA.

Why HCL is more common in certain population groups is an enigma. The population group of the greatest frequency is elderly Ashkenazi Jews, and I have no idea why. But I don't think CRISPR technology would be useful.

Audience member: What criteria do you use for determining which approach for second line therapy. Are certain patients more prone to success with Lumoxiti?

Alan Saven: I don't use Lumoxiti as second line therapy.

What I would do is say how long was your first remission. If your first remission was very brief, I would try something else. If the first remission was very long, then I would probably go back to the same treatment. At relapse I would probably combine it with Rituxan. So if they never got Rituxan at the first treatment, I probably combine it with treatment that I gave at relapse. If they failed 2 courses of a purine nucleoside analogue, I think Lumoxiti is a good choice. I actually personally do not have much experience with Lumoxiti.

Audience member: So what is the median of response with cladribine alone?

Alan Saven: About 4 to 5 years.

Audience member: The Cladribine and Rituxan are supposed to be good for both classic and variant type?

Alan Saven: The definition of variant isn't necessarily BRAF negative. It's a subject of vigorous debate, if that should or shouldn't be part of the definition of classic hairy cell leukemia

Audience member: Because I have all the markers for the classic.

Alan Saven: There are other diseases that can have it to, that's why I don't want to render an opinion until I've seen the slide. Steady marginal zone lymphoma can also give you some of those same markers and the test would be BRAF negative. If I look at the slides and I thought you had hairy cell leukemia and you were BRAF negative, I would probably use the purine nucleoloside analogue and then I'd add Rituxan.

Audience member: Did I understand you correctly when you said that somebody who has had a splenectomy, if they were to get more aggressive you wouldn't treat it?

Alan Saven: No I wouldn't treat them. I would just wait until as long as they could go and you may never require additional therapy. Actually 10 percent of patients with hairy cell leukemia never require any therapy.

In those people that have been splenectomized, I would follow their blood counts either annually or every 6 months. If their blood count deteriorated, then I would consider therapy.

Audience member: How many people go back and have to go through remission. [The patient] was told maybe in 3 months he might have to go through the whole situation again.

Alan Saven: I would like to give cladribine within 2 years of first treatment.

I would probably wait, check the count every week or every other week until the count has normalized and then I actually don't repeat bone marrow. Wait and see if his count is normalized, then I just follow him.

I use this analogy: it's like a chocolate factory, if you enjoy the chocolate you need to go back and look at the factory. Some people routinely go to follow up bone marrow, they get stuck with information that they feel compelled to act upon. That is the most common thing I see, is that people who have got treatment, someone decides to do a bone marrow at month 6, still finds hairy cells and then feel inclined that they have to treat it.

I don't treat it. If the blood count looked good, you don't have to keep looking at the factory. If the blood count has deteriorated, different story.

Also with a clinical study, to know how effective a drug is, you have to go and see how deep the remissions are. Generally the deeper the remission the longer the effect will last. For hairy cell leukemia I'm not sure that is necessarily true. If it’s not broken, don't try to fix it.

Audience member: Would you do bone marrow biopsy at the end? I was treated in April of this year and my numbers have recovered well.

Alan Saven: I wouldn't do a bone marrow as long as your blood counts are fine. There are some people who would do it and then they would give you some additional therapies. I think that is a mistake. People always want to be very aggressive with younger people with illnesses. I'm not sure they necessarily benefit from them.

Audience member: I'm in the military and we have to provide a summary to show that I can continue with my service, can you still give that summary that I am in remission if my blood counts are recovered without doing the bone marrow.

Alan Saven: Yes we call it a hematological remission.

Audience member: We're dealing with a secondary malignancy with my husband. He's already talked to you about it, it’s prostate cancer and it's not necessarily related.

Alan Saven: It could be.

We get patients with hairy cell leukemia, they tend to have an increased tendency of second malignancies, compared to normal people. Prostate cancer is a common problem and it's more common in elderly males than younger males. It's hard to say if it's related. It is a separate problem that has to be dealt with.

It's hard to know if it's a disease or the treatment of the disease. It’s impossible to sort these things out.

Audience member: Would you expect any more combinations in the future, such as different drugs. What do you think?

Alan Saven: Sounds like Rituxan with the Cladribine has been popularized. As frontline therapy, I am not sure that it necessarily improves that which Cladribine does alone.

You can get deeper remission, but deeper remission may come at a price. I don't know. For example, a single course of Cladribine will lower your T-cells into the AIDS range for 6 to 9 months. That is T-cell depletion. When you then add Rituxan to it, you are then going to deplete the B-cells and the T-cells. I don't know what the long-term consequence of that is. There may be no consequence or there may be consequence.

Audience member: If I have the markers for classic hairy cell, I could not have a variant.

Alan Saven: There are things that can mimic hairy cell leukemia, and the fact that you are BRAF negative may not necessarily change the fact that you have hairy cell leukemia. But I don't want to offer you medical advice without seeing your slides.

Audience member: Are there any recommended treatments for fatigue?

Alan Saven: It’s hard to know what's disease and what's life. But if you have disabling fatigue, and you have extensive marrow involvement, we could discuss what we could and couldn't do. But I’d be hard pressed to use fatigue alone as a reason to treat you. I don't know what other medications you're taking. I'm sure hairy cell leukemia causes fatigue, but fatigue is ubiquitous. So it's hard to separate the two.

Audience member: On a recent webinar we talked about shingles

Alan Saven: At some point, you should get the new shingles vaccine.

Audience member: [Question asked about massage and chiropractic therapy.] My doctor's concerned about my bones, saying “I don't want [the chiropractors] popping your back".

Alan Saven: Probably your doctor's giving you good advice. I'm not sure you should be seeing a chiropractor. But massage should be fine.

Audience member: My husband’s doctor wants him to do the shingles virus injection.

Alan Saven: I think it's good advice. Shingles is a nasty aliment, some people get it very bad, very painful. Hairy cell leukemia patients getmore infections than other patients. I think that's probably a good idea for old people, and especially patients with hairy cell leukemia. Don't get the live vaccine. There's a protein vaccine. It's called Shingrix.

Audience member: Can we get all the vaccines?

Alan Saven: Any dead vaccine I think is okay. There are various live vaccines that I would be nervous about, depending on your proximity to treatment.

Audience member: But dead vaccines are okay?

Alan Saven: They should be fine.

Audience member: My father is going through fourth or fifth treatment.

Alan Saven: Lumoxiti is something that I would use for someone who's gone through all the approved medication and clearly isn't responding. It's not something I'd use early on.

Audience member: There are a lot of trials going on, combining vemurafenib.

Alan Saven: I think if you participate in a trial great, if you don’t participate in the trial, I would use Vemurafenib alone.

Audience member: And there's one using Obinutuzumab, which is being tested as a front line therapy.

Alan Saven: Ibrutinib is sort of very similar to Rituximab. It's a new and improved Rituximab.

Audience member: Do you have a personal view on one versus the other?

Alan Saven: Rituximab is much better tolerated. Ibrutinib can show infectious complications. But if the data comes out very strong, then it would be worth those things.

Audience member: Can onset Diabetes type 2 change to type 1, because of hairy cell?

Alan Saven: No.

Audience member: Do bone marrow biopsies cause continued back pain?

Alan Saven: No, it shouldn't, unless this was done by someone who doesn’t know what they’re doing.

Audience member: Is weight gain a side effect of Cladribine?

Alan Saven: No. I think what happens is that you have untreated disease or are symptomatic; the spleen pushes on the stomach. When the disease is in remission, the spleen shrinks, increasing the appetite, and when you eat more, you gain weight. I think people often have big spleens pushing on their stomach. There's a medical term called satiety. They get full very easily from a big spleen.

I tell people not to eat certain things. This hasn't been studied in hairy cell leukemia, but it has been studied in acute leukemia. And people who had a regular diet, with whole fruits and vegetables, did just as well with infections as people who were in a bubble. It makes no difference.

Life is short. Enjoy every day.

There are no dietary restrictions. Obviously, you should have a healthy diet, for cardiovascular reason, but not in terms of hairy cell leukemia.

Audience member: If you’re treated with moxe and relapse later, could you be treated with moxe again?

Alan Saven: I think you can; I don't know what the magical remission duration is. So I think if you have a good remission duration, there's no reason why you couldn’t receive it again.

I wouldn't give it to you if you had a toxic experience. But, if it had gone successfully with a good remission duration, go ahead.

Audience member: Do you see any other immunotoxins developed in the future for hairy cell leukemia?

Alan Saven: I think there'll be immunotoxins that are probably developed for other illnesses that can apply to hairy cell leukemia. Hairy cell leukemia is not a common malignancy, so I doubt that it will be developed For hairy cell leukemia.

With most illnesses you don't get five different therapies and treatment that has stood the test of time. But you’ve got a rare illness, and if you’re not doing well, maybe you should try getting connected with people who have some experience treating the disease.

I think everybody's confident in treating frontline and number two. For number three and onwards, you have to make sure the diagnosis is correct. Cladribine doesn't only work in hairy cell leukemia, it works in all the low-grade lymphomas. And whenever we put people on clinical trials, we get the slides so we can make sure the diagnosis was correct. Probably the error rate is about five to 10 percent. People think that it’s hairy cell leukemia and it's not. And vice versa.

So, the first thing's to get the diagnosis correct

Audience member: So, in hairy cell leukemia, is it considered the CLL.

Alan Saven: No, it's part of the low grade non-hodgkin’s lymphomas, it's a low-grade lymphoma.

Audience member: [Question about what causes hairy cell leukemia.]

Alan Saven: There is no good theory as to what causes hairy cell leukemia. With most malignancies, you can trace it back to the cell; as far as we know with HCL, there's no good theory as to what causes it. In fact, no one knows what the normal counterpart is of the hairy cell.

Audience member: Do you ever go back to Cladribine?

Alan Saven: Yes, especially if they do well the first time and if they exhausted existing therapies, you can go back.

Audience member: Hairy cell leukemia isn't hereditary, right?

Alan Saven: Your chance is no greater than my children. That said, I've seen a brother and a brother, and I've seen a father and a son. But that's very unusual. But I think, statistically, your chance is not greater than the general population.

Audience member: How could I build up my platelet count?

Alan Saven: You can't build it up yourself. You're not going to exercise your way out of it. You can’t change your diet, how much sun you get exposed to. Whatever's causing it needs to be treated.

Audience member: A bone marrow transplant, or something like that?

Alan Saven: Bone marrow transplants aren't usually done in hairy cell leukemia. There are some cases, but that was ancient literature before there were all of these effective therapies.

This transcript has been edited for clarity.