Perspectives on current and future CLL management in New Zealand by Prof. Dr Robert Weinkove 11 April 2025

Perspectives on current and future CLL management in New Zealand

A presentation by Prof. Dr Robert Weinkove, Haematologist at Wellington Hospital and Clinical Director at the Malaghan Institute.

Dr Weinkove was invited by the CLLANZ Trustees to join our strategic planning workshop held last week in Wellington to present his perspectives on current and future CLL management in New Zealand.

The following is a summary of his presentation:

1. Pharmaceutical expenditure in NZ is relatively low compared to some other countries (e.g. Australia, the UK, the USA), and that NZ haematology services and Day Units are under pressure. He highlighted the July 2022 Te Aho o Te Kahu (Cancer Control Agency) report, “A vision for cancer treatment in the reformed health system”, which described a doubling of systemic anticancer therapy dispensing between 2011 and 2020. He also noted that due to population changes projected by Stats NZ, particularly a growing number of people > 65 years in the coming decades, the incidence of CLL can be expected to rise significantly.
2. PHARMAC’s mandate requires them to contain medicine costs, and that for CLL this might favour fixed-duration therapies. PHARMAC will also consider other factors, such as hospital resources saved and equity of access, in their funding decisions. He noted that PHARMAC is not necessarily restricted to funding medicines within their formal license – for example, first-line venetoclax for TP53-disrupted CLL and obinutuzumab for relapsed CLL are both ‘off-label’ but are PHARMAC-funded. Pharmaceutical companies may be unwilling or unable to request PHARMAC reimbursement for off-label indications, but clinicians or patient groups can make applications for PHARMAC funding in these situations.
3. Funding criteria are sometimes widened during PHARMAC consultations, citing the removal of the requirement for relapse within 36 months for PHARMAC-funded VenR for CLL, which was adopted during a recent consultation for venetoclax for AML.
4. International 1^st line CLL treatment recommendations from various organisations including ESMO, BCSH and the NCCN, either do not recommend chemoimmunotherapy at all, or restrict chemoimmunotherapy recommendations to FCR for fit CLL patients with mutated IGHV (and even then FCR is not the top recommendation).
5. The European 2024 ESMO CLL recommendation which states, “…chemoimmunotherapy such as fludarabine–cyclophosphamide–rituximab (FCR) should only be considered for patients with a good genetic risk profile [defined as mutated immunoglobulin heavy chain variable (IGHV) status and no TP53 aberrations] and a non-complex karyotype and if targeted therapies are not reimbursed.” – and the IGHV mutation status test is not currently available in NZ.
6. Australasian CLL treatment guidelines (last issued in 2023) are currently being reviewed, and the next update is also likely to recommend against chemoimmunotherapy.
7. Data from the GLOW and FLAIR trials, found that ibrutinib & venetoclax is superior to chemoimmunotherapy (obinutuzumab/chlorambucil or FCR, respectively) in terms of progression-free survival (PFS).
8. While FCR and ibrutinib/venetoclax had similar PFS within the subgroup of patients with mutated IGHV (N Engl J Med 2024; 390: 326-37), it may take many years (e.g. a decade or longer of follow-up) to know whether or not the two treatments result in differences in durable response rate within this subgroup. He noted that the fraction of patients this represents is low – only approximately 20% of patients getting first-line CLL therapy in NZ are likely to be (A) fit for full-intensity FCR, and (B) have IGHV mutation, and (C) lack TP53 mutation/disruption. He noted that there are now prospective clinical trial data suggesting that FCR is associated with a higher risk of secondary cancers than the newer targeted therapies such as ibrutinib and venetoclax. He felt that while there is equipoise in terms of efficacy of FCR versus ibrutinib/venetoclax for this group at present, many experts internationally feel that selecting a therapy of known carcinogenicity for this subset of fitter younger patients may not be appropriate.
9. Data from a recent manuscript indicates that Māori have a higher age-adjusted incidence of CLL, and a higher CLL-specific mortality, than do Europeans in New Zealand (Cancer Epidemiology 2024; 93: 102656. doi:10.1016/j.canep.2024.102656). He noted that the July 2022 Te Aho o Te Kahu (Cancer Control Agency) report included a section on access barriers for Māori and specifically recommended systemic anticancer therapies that can be self-administered (e.g. oral therapies), to allow treatment closer to home.
10. In terms of funding gaps in CLL treatments in New Zealand, the lack of funded first line targeted (non-chemotherapy-based) treatments is a major deficit.

Dr Weinkove’s personal view on priorities for funding of CLL treatments in NZ is as follows:

1. 1. Priority 1 (most urgent): First-line fixed-duration venetoclax and ibrutinib for all patient groups. Alternatives to venetoclax/ibrutinib could be obinutuzumab/venetoclax (but this requires intravenous administration, with Day Unit and Inpatient Ward resource implications), or venetoclax with a 2^nd generation BTK inhibitor.
   2. Priority 2 (urgent): A funded treatment for patient’s refractory to both venetoclax and a BTK inhibitor. This is likely to represent a growing group with high unmet need. Non-covalent BTK inhibitors (e.g. Pirtobrutinib or Nemtabrutinib) or BTK degraders (e.g. BGB-16673) appear to be very effective oral treatments in this setting.
   3. Priority 3 (strong preference): Funding of an alternative (2^nd generation) BTK inhibitor instead of ibrutinib (e.g. Zanubrutinib or acalabrutinib), since these agents offer lower cardiac toxicity +/- improved efficacy.
   4. Other options (not as urgent but would offer benefits for many patients): Option of VenR re-treatment (would defer some non-covalent BTKi demand, see Priority 2); Option of a first-line continuous BTK inhibitor for frailer patients instead of fixed-duration venetoclax & ibrutinib; Choice between VenR or a continuous BTK inhibitor at first relapse.

Dr Weinkove:

• noted that others might express different priorities
• reported that he has participated in Advisory Boards, and/or acted as a speaker for, Janssen, Abbvie, MSD and BeiGene within the past 3 years.