Managing Hairy Cell Leukemia in the COVID Era
Covid-19 and HCL
People with Hairy Cell Leukemia (HCL) may be more at risk for serious illness from COVID-19. This is due in part to the medications routinely used in HCL treatment. Cladribine and pentostatin are the two most commonly prescribed chemotherapies for HCL, however, they are known to be immunosuppressive. These medications have a direct impact on B-cells and T-cells, making it harder for the body to respond to specific infections.
If treatment is not required immediately after diagnosis, it is best to employ the watch and wait strategy, during which time patients should make every effort to get the appropriate vaccinations and recommended boosters. If treatment is required, physicians should consider avoiding cladribine and pentostatin and instead consider alternative therapies such as vemurafenib and other BRAF inhibitors. The treatment for HCL is very individualized, and lifestyle and patient goals should be considered as well as COVID-19. Years ago, Dr. Harvey Golomb from University of Chicago concluded that approximately 10% of patients who are newly diagnosed with HCL do not require immediate treatment and their doctors should watch and manage their symptoms. Treatment should be considered if the neutrophil count is less than a thousand, the platelets are less than a hundred thousand, or the hemoglobin is less than 10. If levels are only slightly off, patients’ doctors may monitor their symptoms and blood counts.
Some patients may opt to aggressively treat their HCL with rituximab in combination with cladribine as a first line of treatment. This is an effective combination for treating HCL, however, rituximab suppresses the body’s ability to form antibodies and antibody responses for approximately six months to a year. Low antibodies can reduce the effectiveness of the COVID-19 vaccine. As a result, doctors from HCL Centers of Excellence encourage newly diagnosed patients to receive the COVID-19 vaccine before starting HCL treatment.
Patients currently following a treatment regimen should be tested for antibodies after receiving the vaccine. If patients are shown to have a medium or low antibody level, they often respond well to an additional vaccine dose. Patients may not respond to the COVID-19 vaccine at all if they have a high number of cancerous B-cells present in their bone marrow. BRAF inhibitors, such as vemurafenib), or a combination like dabrafenib and trametinib can be beneficial for these patients. These drugs are not as effective as cladribine and pentostatin, however, they can help patients reach partial or complete remission. This will help to increase the number of normal B-cells, which could result in the COVID-19 vaccine being more effective. After using BRAF inhibitors and receiving the vaccine, patients can look into utilizing other drugs to treat residual disease as needed.
To understand the effectiveness of the COVID-19 vaccines, doctors analyze the spike and nuclear capsid antibodies. Spike antibodies protect patients from being infected and they protect patients from being sick or hospitalized with COVID-19. When patients have a good number of regular B-cells, they usually also produce a higher number of spike antibodies. In addition to the COVID-19 vaccine, precautions should also be followed, such as regular hand washing, social distancing when needed, and wearing a mask.
HCL Treatment
There are several therapies available for HCL treatment. The most popular chemotherapeutic treatments are cladribine and pentostatin. These treatments are highly effective, however, it is estimated that 40-50% of patients will relapse due to the residual disease that can still be detected in the bone marrow. Cladribine plus rituximab is highly effective in eliminating minimal residual disease (MRD) and getting patients to complete remission. Utilizing rituximab either at the same time as cladribine or years later can help prevent patients from needing more treatment in the future. The body gets rid of cladribine very quickly, in about a day or two, whereas rituximab stays in the body for many weeks or months.
There are also several chemo-free treatment options. Vemurafenib and dabrafenib inhibit the BRAF protein present in cancerous cells and Ibrutinib and acalabrutinib block non-pathological proteins such as BTK. If MRD is at a manageable level, it is important not to push other therapies due to risk of immunosuppression and secondary cancers.
HCL Variant
There are several newer therapies available for the variant form of HCL. Patients with HCL variant usually have a P53 mutation, making them resistant to chemotherapies such as pentostatin and cladribine. Whereas cladribine plus rituximab is still commonly used for variant HCL treatment, a recent study found that Ibrutinib is effective for both types of HCL. Ibrutinib is a once daily oral medication that can be taken long term or indefinitely, either until it stops working or side effects occur.
Whereas being MRD free is not completely necessary for patients with classic HCL, it is crucially important for patients with variant HCL. Patients with variant HCL have a better chance of staying in remission if they are MRD free. Some patients found that using delayed rituximab as a second course drug helped to reduce their MRD levels.
Overall, cladribine plus rituximab is effective for getting patients into a good remission for many years, albeit, as was previously mentioned, at the cost of a long and significant reduction in the body’s ability to mount an aggressive antibody response to infections. Research is currently looking into developing and combining newer agents for the safe and effective treatment of variant HCL.
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Source Content
An October 10, 2021 panel on HCL served as a primary source for this blog. >>
Author Information
We gratefully acknowledge the work of Kuyili Velagapudi, Spring 2022 Communications Intern. Kuyili is a Public Health and Communication Studies student at The College of New Jersey.