Kristie L. Kahl: Why is it important for patients to consider joining a clinical trial?
Dr. Robert Kreitman: When you join 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.
Kristie L. Kahl: How can patients learn more about clinical trials they may be eligible for?
Dr. Robert Kreitman: 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
Kristie L. Kahl: Are there certain questions that patients should ask their physicians?
Dr. Robert Kreitman: 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.
Kristie L. Kahl: Can you discuss how MRD is being evaluated in trials right now?
Dr. Robert Kreitman: 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.
Kristie L. Kahl: What are some clinical trials in progress that patients can consider?
Dr. Robert Kreitman: 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.
Kristie L. Kahl: What is your biggest piece of advice for a patient considering joining a clinical trial?
Dr. Robert Kreitman: 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.
Transcription edited for clarity.