Chronic lymphocytic leukemia (CLL) progresses more slowly than acute blood cancer but relapses more frequently, requiring various treatment options. However, only limited treatment options are available in Korea.

In these circumstances, AbbVie Korea recently obtained the nod for Venclexta (ingredient: venetoclax) as the nation’s first and only oral B-cell lymphoma-2 (BCL-2) inhibitor. The Ministry of Food and Drug Safety approved Venclexta (venetoclax) as a monotherapy to treat patients with CLL in a third-line or higher-stage treatment in May.

Korea Biomedical Review met with Kim Jin-seok, a professor at the Hematology Department of Severance Hospital, and Mary Ahn Anderson, a clinician-scientist at Peter MacCallum Cancer Center, who contributed to the development of Venclexta.

The interview focused on how physicians are treating CLL and prescribing the drug in Korea and Australia.

KBR: What are the characteristics of CLL in Korea and Australia?

Mary Ahn Anderson: Around the globe, including Korea and Australia, CLL is highly associated with age. People in their 20s develop the disease exceptionally, but most of the CLL patients are aged 65 or more.

In Australia, CLL is one of the most common blood cancers in adults, and CLL patients are as many as those with hypertension or diabetes. Australian doctors treat several thousands of CLL patients a year. The reason for the high incidence of the disease in the West, unlike in Korea, is still unknown, and we need more research.

Kim Jin-seok: In Korea, the average life expectancy was low at around 60 in the past. I assume this is why the incidence of CLL in the elderly is low.

While CLL is the most common leukemia in the West, it is the rarest leukemia in Korea. The nation adds only 150 to 200 new CLL patients every year. This makes it difficult to check if family history affects the development of the disease.

KBR: As Australia has many CLL patients, it is likely to have established treatment guidelines for CLL excellently. How can you compare CLL treatment guidelines of Australia and Korea?

Anderson: As far as I know, treatment guidelines are almost the same in Australia and Korea. First of all, we consider a CLL patient’s existing disease and age when we choose a treatment option.

For the first-line treatment, we use a chemoimmunotherapy. For younger patients, we do FCR (fludarabine, cyclophosphamide, and rituximab). In some cases, we choose BR (bendamustine and rituximab).

We could use chlorambucil, but patients could quickly relapse or do not respond to the drug.

Before 2011, Australia did not have any other option for patients who relapsed or did not respond to the drug after using chlorambucil. However, researchers developed BCL-2 inhibitors such as Venclexta or Bruton's tyrosine kinase (BTK) inhibitors such as Imbruvica (ibrutinib) to offer more treatment options.

Kim: In Korea, too, we mainly use FCR for young patients. However, those aged 65 or more cannot stand FCR due to cancer-killing toxicity. For the elderly, we should use BR, but BR is not reimbursable in Korea. For patients aged more than 70, doctors combine chlorambucil and obinutuzumab.

The problem of CLL is that it frequently relapses. Physicians regard other types of cancer as cured after a five-year treatment, but CLL requires continuous treatment for 10 to 20 years.

If a young patient gets FCR, the patient has a 50 percent chance of relapse within four or five years. In patients treated with a combo of obinutuzumab and chlorambucil, 50 percent of them experience a relapse. In this case, there is no other option, and we use chlorambucil again. Then, the response time gets much shortened.

In Korea last year, BKT inhibitor ibrutinib received insurance coverage for the second-line treatment of CLL. However, this drug has four to five years of drug response, and half of the patients are expected to relapse within this period.

Anderson: The unmet medical demand for CLL treatment seems to be similar in Australia and Korea. Patients with deleted 17p gene or relapsed CLL have a poor prognosis.

About 5 percent of patients with CLL have a 17p gene defect, and these patients are very unlikely to reach remission with first-line or second-line therapies. About 40 to 60 percent of 17p gene-deficient patients treated with FCR have a very poor prognosis after three or four years. So, we must have various treatment options so that these patients can receive continuous treatment.

Kim: CLL patients who relapse or do not respond, after secondary treatment, have a remaining life expectancy of less than one year. These patients mostly die from an infection. Lymphocytes are cells that are responsible for immunity in the body, and when they fail to function properly, patients will die from infection such as pneumonia or sepsis. Thus, CLL is a severe disease that must be treated timely.

In the past, we did not have any other option after second-line treatment. However, recently, the approval of Venclexta enabled CLL patients to extend their lives.

Venclexta is not only an oral drug but also has fewer side effects, such as hair loss. So, patients can lead a healthy life while getting the treatment for longer life.

KBR: What improvements does CLL treatment need?

Anderson: In Australia, patients with 17p gene or TP53 gene defect have a poor prognosis, but they cannot receive insurance benefit for the use of new drugs. So, we are doing chemoimmunotherapy first.

We can predict the treatment results, and there are more effective treatments. However, we cannot help but do the chemoimmunotherapy first, which makes me feel bad. Such patients can expect a good prognosis if they receive a new therapy, like Venclexta. Thus, we need improvements in reimbursement of new treatments.

Kim: In the case of CLL, physicians use Gleevec, Tasigna, or Sprycel to help patients maintain an average life expectancy similar to that of healthy people.

In foreign countries, CLL is common, and researchers have actively studied the disease to develop various types of new medicines. In Korea, however, it is a rare blood cancer with a small number of patients. This made some drugmakers voluntarily withdraw from application for approval and gave up a local release.

I hope pharmaceutical firms could release new drugs with a new mechanism to help patients continue their treatment, and the government could support the treatment environment so that patients can continue to strive for longer life.