A current overview of medications in the treatment of CLL in New Zealand

A talk presented to the CLL Advocates NZ Board of Trustees on 7 May 2020 by Dr Gillian Corbett MBChB, FRACPath, MRCP, FRACP, Trustee, CLL Advocates NZ  https://clladvocates.nz/about-us/trustees/

Not all CLL patients need treatment. Treatment is offered for progressive disease, increasing lymphadenopathy, anaemia, and/or low platelets, as well as rapidly increasing lymphocyte count.

Patients with mutated heavy genes (about 55%) generally carry a better prognosis than those with unmutated heavy genes. This testing is unfortunately unavailable in NZ.

First line treatment

In New Zealand, FCR (fludarabine, cyclophosphamide, rituximab) is standard treatment for younger patients with CLL, up to around 70-75 years. Fludarabine and cyclophosphamide are generally given orally, once per month for up to 6 courses, and rituximab is given as an intravenous infusion once a month. This treatment is very successful for patients with mutated heavy chain genes, and some may potentially be cured. However those with unmutated heavy chain genes do not respond so well and frequently relapse early. A study has shown that such patients respond well to ibrutinib with a better outcome than FCR. However ibrutinib is not funded to treat CLL in New Zealand.

For older patients (70-85 years) the funded first line treatment is bendamustine and rituximab. Each is given by infusion once per month for up to 6 months. This treatment has been shown to be not so effective for younger patients, for whom FCR is preferred, but is better tolerated by older patients

For older patients or those unfit for bendamustine and rituximab, chlorambucil and obinutuzumab is the funded treatment. Obinutuzumab is a more potent antibody than rituximab and has been shown to be more effective in combination with chlorambucil in these patients.

Venetoclax is funded as first line treatment for patients with del17p chromosomal change. These patients do not generally respond well to the other funded treatments. It targets BCL2 which results in an increased rate of CLL cell death. It is given orally and is generally well tolerated but in some patients with bulky disease it may cause tumour cell lysis which can result in kidney damage. Such patients may require hospitalisation for intravenous fluid and supportive care.

Second line treatment

Patients who relapse within 3 years of previous treatment are eligible for venetoclax and rituximab. The venetoclax is to be used for up to 24 months. It is given orally.


There are studies overseas of combining ibrutinib and venetoclax treatment with a view to achieving negative minimal residual disease and possibly cure of CLL. The results of these studies are awaited.

Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor which interferes with CLL cell growth. It is effective in the majority of de novo and relapsed patients with CLL. It is not known to cure CLL. It is generally well tolerated. Other BTK inhibitors that are more targeted are being trialled eg acalabrutinib and zanubrutinib. Tauranga and Waikato Hospitals are part of an international clinical trial comparing ibrutinib to zanubrutinib in relapsed CLL.

Other areas of research are in the development of immune therapies eg CAR-T cells to target CLL cells.