Lisa Machado is the founder of the Canadian CML Network (cmlnetwork.ca), a national patient support organization based in Toronto, Ontario, Canada. She has been living with chronic myeloid leukemia since 2008. She can be reached at email@example.com.
Patients with CLL can benefit from improved treatment options, but some are waiting for equal opportunity to testing and drugs.
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL), the most common leukemia in adults, has been the focus of headlines in recent years because of enormous progress in its treatment.
Within the past six years or so, seven novel drugs have been approved by Health Canada to treat the condition. Four are monoclonal antibodies: Rituxan (rituximab), Campath (alemtuzumab), Gazyva (obinutuzumab) and Arzerra (ofatumumab). Three are small molecule inhibitors: Imbruvica (ibrutinib), Zydelig (idelalisib) and Venclexta (venetoclax). Treanda (bendamustine), a standard chemotherapy agent, was recently approved in combination with Rituxan.
These new treatments would be great news for both clinicians and patients, except that they are not equally accessible across the provinces. In fact, Canada's numerous health systems mean that what patients have access to is often determined by their postal code.
Still, as CLL care continues to change, so does the outlook for those living with it.
CLL originates in the bone marrow, where blood cells form. The B lymphocytes, a mature type of white blood cell, start to grow and survive beyond their normal life span. These leukemia cells may look somewhat normal under a microscope, but they reproduce too rapidly, survive longer than normal cells and crowd out other blood cells — mainly the red cells, which are involved in oxygen delivery, and platelets, cell fragments that help with blood clotting. In severe cases, the number of neutrophils, white blood cells that are part of the immune system, may be affected.
The cancer cells receive growth and survival signals from both the bone marrow and the lymph nodes, which causes them to circulate through the blood system on a regular basis. As a result, patients may have no symptoms at diagnosis except for an abnormal lymphocyte count.
Each year, about 2,500 people are diagnosed with CLL in Canada, and about 600 people die from it.
At diagnosis, most people with CLL are not aware of having any symptoms, says Versha Banerji, MD, FRCPC, a hematologist in the CLL Clinic at the University of Manitoba and CancerCare Manitoba. “Very often, the primary physician will see an elevated white blood cell count during a routine blood test,” she says. “Sometimes patients may have fevers, chills and noticeable weight loss, but this is mostly in advanced stages of the disease.”
These symptoms — in addition to fatigue, changes in appetite and sleep, bleeding or bruising easily, and/or enlargement of the spleen, liver or lymph nodes — call for a visit to a doctor.
CLL can be diagnosed by a simple blood test. “If a person comes in with a high white cell count, we basically use flow cytometry (a type of electronic cell analysis) to look for CLL cells,” says Banerji, who sees about 1,000 patients every year. “If the result is positive, the patient is sent to the CLL clinic for a treatment plan discussion.”
There are two staging systems that doctors use to predict disease progression: the Rai Staging System and the Binet Staging system. Banerji uses the Rai system, which classifies CLL into five stages ranging from low-risk to varying degrees of high-risk, which are associated with the presence of enlarged lymph nodes and/or spleen, elevated lymphocyte counts, a low platelet count and/or low levels of hemoglobin, a protein whose job is to transport oxygen within the body.
“Determining the right treatment plan for CLL is more complicated than it has ever been,” Banerji says.
Initial standard treatments can range from watchful waiting to chemotherapy for intermediate- or high-risk CLL.
Targeted therapies are used after chemotherapy if the cancer is no longer responding or has recurred. Stem cell transplants are still available, but are no longer considered part of routine care. Banerji considers three factors in determining treatment: age, fitness and molecular markers.
Age is broken down into two categories: 66 years and above and 65 years and below. Fitness is scored using the CIRS illness rating scale to predict a patient’s ability to tolerate certain treatments, with 6 or below being considered fit and 6 or above deemed unfit. This grading is subjective but has been used heavily in clinical trials for CLL. Identifying molecular markers, such as genetic mutations that are treatable with drugs, is also very important.
“Molecular markers can help us determine which patients can live for long periods without treatment, and those who will have progressive disease,” she says. “The ability to identify these markers has really changed the CLL experience for many people.”
One example is a test that looks for a mutation in the IgVH gene.
“We know that people with IgVH mutations tend to have better outcomes than those with unmutated IgVH,” she says. “But we need the test to tell us, and in Manitoba, for example, we don’t have access to it.”
Unfortunately, not every patient with CLL has access to these tests.
“Canada is fragmented when it comes to testing capabilities,” says Banerji. “It is frustrating as a clinician and for patients who may not be getting treatment that is as appropriate and targeted as it could be.”
As in several other provinces, unless there is a compassionate program offered by a manufacturer or the patient has private insurance, the only options left are to pay out of pocket, which can be quite burdensome, or to opt out.
This has prompted Banerji to take on the role of advocate in addition to her busy role as a clinician and senior scientist. Together with her clinical team, she is working with the provincial diagnostic labs and CancerCare Manitoba to make treatment-guiding tests like the one for IgVH available in Manitoba.
Even without more universal access to such tests, the outlook for patients with CLL has improved greatly. “We have so many more options in CLL now than we did even 10 years ago, and it has changed everything,” Banerji says. “Early discussions with patients used to be desperate. Now we are more hopeful. Before, we would tell a patient that chemotherapy or a transplant was the treatment, and we would deal with side effects as we went along. Now, we have choices.”
Patients are also playing a more active role in their own health.
“Patients are engaged more than ever,” she says. “We not only talk about prognosis, but also about what they want out of their life and what their goals are for the future.”
Despite all the good news in CLL, a cancer diagnosis is still scary for most. Connecting with a community that is familiar with the journey can be critical not only to better understanding the disease, but to moving forward through treatment.
One of these communities is the Canadian CLL Patient Advocacy Group, which can be reached at cllpag.ca. Other resources include the Leukemia & Lymphoma Society of Canada, Lymphoma Canada and Lymphoma Coalition.
“CLL can be a challenging diagnosis,” says Deborah Baker, past chair of the CLL Patient Advocacy Group’s Board of Directors. “One way that patients and caregivers can feel more in control is by accessing a community of people who share their experiences. These people are valuable sources of education, advice and support, and in the end, these connections can greatly improve outcomes.”
This article is part of the Bringing the CLL Community Together program. Funding is provided by an unrestricted educational grant from Pharmacyclics, an AbbVie Company, and Janssen Biotech, Inc.