IbrutinibIMBRUVICA
Previously untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), in combination with venetoclax, for patients suitable for fludarabine-based chemoimmunotherapy.
Decisions on record
- Meeting Jul 2024 Noted Chronic lymphocytic leukaemia and small lymphocytic lymphoma with 17p deletion no PSD
- Meeting Mar 2024 Recommended Chronic lymphocytic leukaemia (CLL) or Small lymphocytic lymphoma (SLL)
- Meeting Mar 2023 Noted Chronic lymphocytic leukaemia (CLL)/Small lymphocytic leukaemia (SLL) no PSD
- Meeting Dec 2022 Not recommended Chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), in combination with venetoclax, for treatment of previously untreated disease
- Meeting Nov 2022 Noted Chronic lymphocytic leukaemia or small lymphocytic lymphoma no PSD
- Meeting Nov 2022 Noted Chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma no PSD
- Meeting Dec 2021 Noted Indication not stated no PSD
- Meeting Nov 2021 Noted Chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) no PSD
12 earlier decisions
- Nov 2020 Recommended Chronic lymphocytic leukaemia (CLL); small lymphocytic lymphoma (SLL); mantle cell lymphoma
- Nov 2019 Recommended Chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL)
- Mar 2018 Recommended Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) and relapsed or refractory mantle cell lymphoma (MCL)
- Nov 2017 Not recommended Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL)
- Nov 2017 Not recommended Indicated for the treatment of: •patients with mantle cell lymphoma who have received at least one prior therapy. •adult patients with CLL/SLL who have received at least one prior therapy or adult patients with previously untreated CLL/SLL •Patients with CLL/SLL with deletion 17p; and •adult patient
- Mar 2017 Recommended Relapsed or refractory chronic lymphocytic leukaemia (CLL). Relapsed or refractory small lymphocytic lymphoma (SLL). no PSD
- Nov 2016 Not recommended Relapsed or refractory mantle cell lymphoma
- Nov 2016 Not recommended Ibrutinib is indicated for the treatment of patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) in patients who have received at least one prior therapy, or as first line in CLL patients with 17p deletion; and mantle cell lymphoma (MCL) in patients who have received
- Aug 2016 Not recommended Chronic lymphocytic leukaemia and small lymphocytic lymphoma no PSD
- Mar 2016 Deferred Chronic lymphocytic leukaemia and small lymphocytic lymphoma
- Nov 2015 Deferred Chronic lymphocytic leukaemia and small lymphocytic lymphoma
- Jul 2015 Not recommended Chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL)
Access path
- TGA registered · IMBRUVICA
TGA label narrower than the PBS population
- Jul 2015Not recommended
vs rituximab plus chlorambucil
- Nov 2015Deferred
Comparator changed: rituximab plus chlorambucil → rituximab + chlorambucil
- Mar 2016Deferred
Comparator changed: rituximab + chlorambucil → chlorambucil plus rituximab (ofatumumab…
- Nov 2016Recommended
Comparator changed: chlorambucil plus rituximab (ofatumumab monotherapy also used in…
- Nov 2016Not recommended
Comparator changed: chlorambucil plus rituximab (ofatumumab monotherapy also used in…
- Nov 2017Not recommended
Ibrutinib superiority to obinutuzumab+chlorambucil not sufficiently demonstrated (based on indirect comparisons rather…
- ↻ resubmittedNov 2017Recommended · restricted
Comparator changed: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine…
- Mar 2018Recommended · restricted
Comparator changed: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine…
- Nov 2019Recommended · restricted
Comparator changed: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone…
- Nov 2020Recommended
Comparator changed: obinutuzumab + chlorambucil → ibrutinib 140 mg capsules
- Dec 2022Not recommended
Comparator changed: ibrutinib 140 mg capsules → fludarabine, cyclophosphamide, and…
- ↻ resubmittedMar 2024Recommended
Comparator changed: fludarabine, cyclophosphamide, and rituximab (FCR) → venetoclax +…
- PBS listing · Authority Required
From the public summary
7.1 The PBAC recommended extending the listing of ibrutinib, to include use in combination with venetoclax (IBR+VEN), for the treatment of patients with previously untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).PSD · Mar 2024
The PBAC’s recommendation for listing was based on its assessment that the cost- effectiveness of IBR+VEN would be acceptable if it were cost-minimised against venetoclax in combination with obinutuzumab (VEN+OBI). In making its recommendation, the PBAC also considered the clinical need and the equity of access advantages associated with an all-oral therapy.PSD · Mar 2024
The PBAC considered that the cost-effectiveness of The nominated main comparator in the resubmission was ibrutinib + venetoclax was unable to be reliably assessed venetoclax + obinutuzumab. The clinical claim of noninferior due to the uncertain magnitude of benefit, which relied on efficacy underpinning the cost-minimisation was based on the immature data from the CAPTIVATE study, and an results of a Bucher method indirect comparison and an unanchored, …PSD · Mar 2024
The PBAC considered a cost comparison of ibrutinib + The resubmission presented a cost-minimisation approach venetoclax and venetoclax + obinutuzumab would be comparing treatment with fixed duration ibrutinib + venetoclax informative in any resubmission (para 7.10). to fixed duration venetoclax + obinutuzumab.PSD · Mar 2024
• Ibrutinib + venetoclax is superior to FCR in terms of efficacy and at least non-inferior in terms of safety, with a different safety profile compared to FCR, and a reduced risk of developing secondary primary malignancies.PSD · Mar 2024
Source: Table 1.1 of the resubmission; Table 1, p1 of the ibrutinib Public Summary Document, December 2022 intracycle PBAC meeting.PSD · Mar 2024
6.2 The PBAC noted and welcomed the input from individuals (16), health care professionals (1 group of clinicians) and from the 2 organisations, Lymphoma Australia, and the Leukaemia Foundation, via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with ibrutinib including improvements in disease progression, white blood cell counts, and energy levels.PSD · Dec 2022
6.3 The PBAC recalled that a clinician consultation was held on 1 December 2022 to discuss the treatment of CLL /SLL in relation to the existing PBS treatment algorithm and the new drug regimens proposed for PBS-listing in the context of the evolving treatment landscape. The key points were:PSD · Dec 2022
Cost-effectiveness
Cost-minimisation analysis performed; no ICER calculated by design.
The submission considered the listing of ibrutinib tablets would be cost neutral to the PBS as ibrutinib tablets are expected to substitute for ibrutinib capsules. PSD · 2020
Decision context
PopulationAdults with previously untreated CLL/SLL who would otherwise be considered fit for treatment with fludarabine-based chemoimmunotherapy; receiving fixed duration ibrutinib (420 mg daily for 3 cycles lead-in, then continued with venetoclax for 12 further cycles) in combination with venetoclax.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2024 | Recommended | venetoclax + obinutuzumab | — | RCT · PFS |
| Dec 2022 | Not recommended | fludarabine, cyclophosphamide, and rituximab (FCR) | — | RCT · PFS |
| Nov 2020 | Recommended | ibrutinib 140 mg capsules | — | RCT · Bioequivalence |
| Nov 2019 | Recommended · restricted | obinutuzumab + chlorambucil | — | RCT · PFS |
| Mar 2018 | Recommended · restricted | rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) | $45k–75k | RCT · OS |
| Nov 2017 | Not recommended | obinutuzumab+chlorambucil (and rituximab+chlorambucil as secondary comparison) | $75k–105k | RCT · PFS |
| Nov 2017 | Recommended · restricted | R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) | — | RCT · PFS |
| Nov 2016 | Recommended | rituximab plus chlorambucil | — | RCT · OS |
| Nov 2016 | Not recommended | R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) | — | RCT · PFS |
| Mar 2016 | Deferred | chlorambucil plus rituximab (ofatumumab monotherapy also used in trial) | $45k–75k | RCT · OS |
| Nov 2015 | Deferred | rituximab + chlorambucil | $45k–75k | RCT · PFS |
| Jul 2015 | Not recommended | rituximab plus chlorambucil | — | RCT · PFS |
Codependent tests
| Service | Biomarker | MSAC outcome | Year |
|---|---|---|---|
| Genome-wide microarray testing for multiple myeloma and chronic lymphocytic leukaemia | del(17p) and other chromosomal abnormalities | supported | 2019 |
| 17p deletion testing by FISH for CLL/SLL | 17p deletion (del(17p)) | supported | 2019 |
| 17p deletion testing (FISH) for CLL/SLL | 17p deletion (del(17p)) | supported | 2020 |
Consumer voice
Consumer input from 64 individuals, 6 health professionals, and 3 organisations described benefits of ibrutinib + venetoclax including improved quality of life, reduced fatigue, ability to work, improved mental health, and potential for complete disease remission. Health professionals noted potential safety concerns (immunosuppression, AF, bleeding) while patients reported minimal side effects; mo
improved quality of life due to reduced fatigue, an ability to work and improved mental health Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to patients suitable for fludarabine-based chemoimmunotherapy and mandates fixed-duration ibrutinib-venetoclax combination, versus TGA's broader monotherapy or multiple combination options.