Chronic Lymphocytic Leukemia in China

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Chronic Lymphocytic Leukemia in China
By Robert Peter Gale, MD, PhD
Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London

Did you know chronic lymphocytic leukemia (CLL)—the most common adult leukemia in Western countries—is 10 to 20 times less frequent in Han Chinese people? While CLL affects about 4.6 out of every 100,000 people of European descent annually, the rate in China is just 0.2 to 0.6 per 100,000. This dramatic difference has puzzled researchers for decades—and new studies are shedding light on why.

Why Is CLL So Rare in China?

Most cases of CLL are asymptomatic in early stages, meaning the cancer is often discovered by chance during a routine blood test (CBC) for unrelated issues (like a job physical or checkup for another illness). For years, this led to ascertainment bias: CLL seemed rare in China because fewer people had access to regular CBCs, especially in rural areas.

Today, however, CLL diagnoses are rising—and not because more people are getting sick. Three key factors explain the shift:

  1. Wider testing: CLL diagnostic tools (like multi-parameter flow cytometry) are now available in more parts of China.
  2. Better access to care: Health insurance coverage has expanded, so more people can visit large city hospitals for specialized care.
  3. Increased health awareness: Chinese adults are more likely to get routine checkups and seek medical help for minor symptoms.

But these changes only tell part of the story. Even in resource-rich Asian countries like Japan and Korea—and among Asian Americans (where CLL rates are 5 to 10 times lower than white Americans)—CLL remains uncommon. This points to a strong genetic basis for the lower risk.

The Genetic Link to CLL Risk

Studies of Asian immigrants to the U.S. and Canada confirm that genetics play a major role. For example:

  • HapMap analysis: Gene variants linked to higher CLL risk in Europeans (like certain single-nucleotide polymorphisms, or SNPs) are rare in Han Chinese.
  • Family history: While CLL runs in families for people of European descent, no such pattern has been found in Chinese populations—likely because underdiagnosis masks familial risk.

Mutations common in CLL also differ between Chinese and European patients:

  • Del(13q14): This chromosomal deletion (an early driver of CLL) is found in about half of both groups.
  • SF3B1: Mutations in this gene (tied to chemotherapy resistance) are less frequent in Chinese patients.
  • MYD88/KMT2D: These mutations are more common in Chinese CLL patients, though their impact on prognosis is still being studied.

How CLL in China Compares to the West

At first glance, Chinese CLL patients seem different from their European counterparts:

  • Younger age at diagnosis: The median age in China is 60, compared to 65–70 in Europe.
  • More advanced disease: 45%–60% of Chinese patients are diagnosed at Binet stage B or C (advanced), versus 20%–40% in Europe.

But these differences are mostly due to who gets tested. As more older adults in China get CBCs for routine care or unrelated illnesses, early-stage CLL diagnoses are rising. The “worse outcomes” myth? It’s largely a result of late detection in the past—not faster disease progression.

New Treatments Transforming CLL Care in China

For decades, the only treatment for CLL in China was chlorambucil, a old chemotherapy drug with limited efficacy. Today, targeted therapies are changing the game:

BTK Inhibitors

Bruton tyrosine kinase (BTK) inhibitors—like ibrutinib, zanubrutinib, and orelabrutinib—are now approved in China. Clinical trials show they work as well for Chinese patients as they do for Westerners:

  • Ibrutinib: A 2022 study found 30-month progression-free survival (PFS) of 66% in advanced CLL patients—similar to European results. Importantly, ibrutinib had a lower risk of hepatitis B virus (HBV) reactivation (a critical concern in China, where 10% of people have latent HBV) compared to rituximab.
  • Zanubrutinib: A phase 2 trial reported 87% 1-year event-free survival in relapsed/refractory CLL patients.
  • Orelabrutinib: Early data show rapid, deep responses in advanced cases.

Bcl-2 Inhibitors

Venetoclax, a Bcl-2 inhibitor used to treat high-risk CLL (like patients with del(17p) or BTK inhibitor resistance), is under study in China. Local drug companies are also developing new Bcl-2 inhibitors, with trials underway (e.g., NCT04494503).

Cell Therapies

China is a global leader in CAR-T and CAR-NK cell therapies. There are 21 active CAR-T trials and 3 CAR-NK trials for CLL registered on ClinicalTrials.gov—offering hope for patients who fail other treatments.

What’s Next for CLL in China?

The biggest question remains: Why is CLL so rare in Chinese people? Researchers hypothesize that an ancient infectious agent (present in Asia 45,000 years ago) may have selected for genetic traits that reduce CLL susceptibility. Unlocking this mystery could lead to new ways to prevent CLL worldwide.

For now, the biggest win is access to better treatments. BTK inhibitors like ibrutinib and zanubrutinib are covered by public insurance, and more drugs are on the way. As testing becomes more widespread, early diagnosis will rise—and so will survival rates.

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