Transcript
My name is Jacqueline Barrientos. I am associate professor at Hofstra School of Medicine in Long Island. I work at the CLL Research and Development program.
The topic that I spoke today is about hairy cell leukemia and how this is changing over the last couple of years. I essentially started off talking about, historically, we first started learning about this disease in the 1950s. In 2008, it was recognized that there were 2 different subtypes including classic hairy cell leukemia and variant hairy cell leukemia.
In 2011, the Italian group discovered that the vast majority of patients with hairy cell leukemia, the classic form, they carry a mutation of the BRAF, a gene mutation that is also found in patients with melanoma — in about half of them.
Essentially, over time, the therapy moved from it being splenectomy or taking out the spleen and interferon, which could achieve a good response rate, but not good complete remission rates to then the novel agents. When they came at the time, it was cladribine and pentostatin, 2 purine analogs, that showed not only very good response rates, but the people that were able to achieve a complete remission could go into remission for more than 10 years or higher.
In some people, even though it's not a cure, many of them behaved as if they had been cured. The problem with the disease is that, after those 10 years, people relapse. The second time around, the overall response rate is smaller and the complete remission rates go down. The time between therapies starts to shrink.
That's when we started to find that it's an orphan disease when people have relapsed refractory hairy cell leukemia. These patients that do relapse within the first 2 years are at high risk because those patients truly didn't respond to the original purine analog. For those patients, it would be best to use a drug such as regorafenib, which at this moment is not FDA approved for the treatment of hairy cell leukemia.
However, based on the data that has been published in The New England Journal by both the Italian and the American groups, we know that the drug works as monotherapy in patients with relapsed refractory disease or high-risk disease, so it's part of the NCCN Guidelines.
Another additional therapy option is participation in a clinical trial or using an alternative purine analog in combination with rituximab. If you relapse for a second time, two or more prior lines of therapies, then you can use another couple of drugs.
First of all, we always recommend to use a clinical trial or participate in a clinical trial or refer your patients for a clinical trial. After 2 lines of therapy, those are the patients that are the sickest. You need to refer them because we may have availability to drugs that are not currently commercially available.
We have a Hairy Cell Leukemia Consortium and centers of excellence. Our group is one of them. There are several groups across the nation. If the patient is fit, they would benefit from referral to one of these centers for a second opinion.
For second-line therapy or above, there's a new drug called moxetumomab. That drug is a toxin conjugate that targets CD22. The original monoclonal antibody was reported back in 2001, but it wasn't until 2018 that it was recently approved by the FDA particularly because it's difficult to have a large relapse refractory group of patients, one.
The other reason is because it also has some certain toxicities that need to be known by the providing physicians because it may cause harm to your patients. One of them is capillary leak syndrome. The other one is hemolytic uremic syndrome, HUS.
For both potential complications, there's several interventions that the company that manufactures the product usually recommends both to the patient and the physician. It does achieve, in many patients, a complete remission and also a good response rate.
Last but not least, vemurafenib was recently presented in combination with rituximab by Enrico Tiacci and his group from Italy at EHA in 2019. The response rate was spectacular in terms of complete remission achievement. 96% of the patients were able to achieve a complete remission with a combination strategy.
It brings us to this idea that maybe, in the future, we will be able to do a head-to-head comparison of a targeted agent in combination with a monoclonal antibody against chemotherapy or chemo-immunotherapy, just like we saw with CLL where ibrutinib in combination with rituximab was compared against 2 standards of care, FCR or BR in young and fit.
We saw that the patients receiving the targeted agents actually did better. We might be starting to see this soon. The group from Dr Jae Park in the United States is going to present his data on patients treated, front-line, with vemurafenib in combination with obinutuzumab for front-line, fixed-duration regimen at ASH this year.
If the results are good, maybe it will be a consolidation of what we think. Vemurafenib, in combination with a monoclonal antibody, may be able to achieve deeper responses and, hence, allow the patients to be in remission for a longer period of time.
We still haven't achieved a cure for this disease, but we're moving towards milder therapies that are safer and better tolerated and that do not require the patients to be on the drug forever. Dr Jae Park presented some data of people that stopped vemurafenib because it's a fixed-dose regimen. At the time of relapse, they reinitiated therapy with vemurafenib, and they responded really well.
It's very encouraging for our patients. I encourage physicians and patients to seek guidance at any time that they have any questions from the group of the Hairy Cell Leukemia Consortium. It's on the Web, and you can reach us. We, as a group, discuss difficult cases because we all want the best for our patients.
