Bendamustine funding approved

Medicines

Decision

PHARMAC is pleased to announce the approval of an agreement with Janssen-Cilag Pty Ltd (Janssen) for the listing of bendamustine.

This was the subject of a consultation letter dated 15 May 2017. The funding of bendamustine means that a new pharmaceutical used to treat chronic lymphocytic leukaemia (CLL) and indolent Non-Hodgkin lymphoma (iNHL) will be funded, subject to restrictions, from 1 July 2017. 

The proposal was broadly approved as consulted on except for small changes to Special Authority criteria, in that:

  • the bendamustine criteria were amended to allow patients with CD20 negative iNHL (1-2% of patients) to access bendamustine monotherapy, and
  • the rituximab criteria were amended to remove the requirement for patients to have good renal function (creatinine clearance ≥ 30 ml/min) for the treatment of CLL.

Details of the decision

Bendamustine

  • Bendamustine (Ribomustin) will be listed in Section B and in Part II of Section H of the Pharmaceutical Schedule from 1 July 2017 at the following prices and subsidies (ex-manufacturer, excluding GST): 

Presentation

Pack size

Proposed price and subsidy

Inj 25 mg vial

1

$271.35

Inj 100 mg vial

1

$1085.38

Inj 1 mg for ECP

1 mg

$11.40*

  • A confidential rebate will apply to Ribomustin that will reduce its net price to the Funder.
  • Bendamustine will be listed in the Pharmaceutical Schedule as a Pharmaceutical Cancer Treatment only (PCT only – Specialist), meaning that only DHB hospitals will be able to claim for its use.
  • Bendamustine will be listed in Section B of the Pharmaceutical Schedule, for claiming purposes only, subject to the following Special Authority criteria:

Initial application — (treatment naive CLL) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

1. The patient has Binet stage B or C, or progressive stage A chronic lymphocytic leukaemia requiring treatment; and
2. The patient is chemotherapy treatment naive; and
3. The patient is unable to tolerate toxicity of full-dose FCR; and
4. Patient has ECOG performance status 0-2, and
5. Patient has a Cumulative Illness Rating Scale (CIRS) score of <6; and
6. Bendamustine is to be administered at a maximum dose of 100 mg/m2 on days 1 and 2 every 4 weeks for a maximum of 6 cycles.

Note: ‘Chronic lymphocytic leukaemia (CLL)’ includes small lymphocytic lymphoma (SLL). Chemotherapy treatment is considered to comprise a known standard therapeutic chemotherapy regimen and supportive treatments.

Initial application — (Indolent, Low-grade lymphomas) – only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 9 months for applications meeting the following criteria:

All of the following:

1. The patient has indolent low grade NHL requiring treatment; and

2. Patient has a WHO performance status of 0-2; and

3. Either:

3.1.    Both:

3.1.1.  Patient is treatment naive; and
3.1.2.  Bendamustine is to be administered for a maximum of 6 cycles (in combination with rituximab when CD20+); or

3.2.    All of the following:

3.2.1.  Patient has relapsed refractory disease following prior chemotherapy; and
3.2.2.  The patient has not received prior bendamustine therapy; and
3.2.3.  Either:

3.2.3.1.  Both:

3.2.3.1.1.  Bendamustine is to be administered for a maximum of 6 cycles in relapsed patients (in combination with rituximab when CD20+), and
3.2.3.1.2. Patient has had a rituximab treatment-free interval of 12 months or more; or

3.2.3.2.    Bendamustine is to be administered as a monotherapy for a maximum of 6 cycles in rituximab refractory patients.

Renewal — (Indolent, Low-grade lymphomas) – only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 9 months for applications meeting the following criteria:

Both:

1. Patients have not received a bendamustine regimen within the last 12 months; and

2. Either:

2.1    Both:

2.1.1      Bendamustine is to be administered for a maximum of 6 cycles in relapsed patients (in combination with rituximab when CD20+), and
2.1.2      Patient has had a rituximab treatment-free interval of 12 months or more; or

2.2    Bendamustine is to be administered as a monotherapy for a maximum of 6 cycles in rituximab refractory patients.

Note: ‘indolent, low-grade lymphomas’ includes follicular, mantle cell, marginal zone and lymphoplasmacytic/ Waldenström’s macroglobulinaemia.

  • The same restrictions will apply in Part II of Section H of the Pharmaceutical Schedule (the Hospital Medicines List; HML).

Rituximab

  • The initial Special Authority criteria for rituximab for CLL will be amended in Section B and H of the Pharmaceutical Schedule from 1 July 2017 as follows (changes in bold and strikethrough):

Initial application — (Chronic lymphocytic leukaemia) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

1.   The patient has progressive Binet stage A, B or C chronic lymphocytic leukaemia (CLL) requiring treatment; and
2.   The patient is rituximab treatment naïve; and
3.   Either:

3.1 The patient is chemotherapy treatment naïve; or
3.2 Both:

3.2.1 The patient’s disease has relapsed following no more than three prior lines of chemotherapy treatment; and
3.2.2 The patient has had a treatment-free interval of 12 months or more if previously treated with fludarabine and cyclophosphamide chemotherapy; and

4.   The patient has good performance status; and
5.   The patient has good renal function (creatinine clearance ≥ 30 ml/min); and

6.5. The patient does not have chromosome 17p deletion CLL; and

7.6. Rituximab to be administered in combination with fludarabine and cyclophosphamide or bendamustine for a maximum of 6 treatment cycles; and

8.7. It is planned that the patient receives full dose fludarabine and cyclophosphamide (orally or dose equivalent intravenous administration) or bendamustine

Note: 'Chronic lymphocytic leukaemia (CLL)' includes small lymphocytic lymphoma. A line of chemotherapy treatment is considered to comprise a known standard therapeutic chemotherapy regimen and supportive treatments. 'Good performance status' means ECOG score of 0-1, however, in patients temporarily debilitated by their CLL disease symptoms a higher ECOG (2 or 3) is acceptable where treatment with rituximab is expected to improve symptoms and improve ECOG score to <2.

Renewal application – (Chronic lymphocytic leukaemia) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

1. The patients disease has relapsed following no more than one prior line of treatment with rituximab for CLL; and
2. The patient has had a rituximab treatment–free interval of 36 months or more; and
3. The patient does not have chromosome 17p deletion CLL; and
4. It is planned that the patient receives full dose fludarabine and cyclophosphamide (orally or dose equivalent intravenous administration) or bendamustine; and
5. Rituximab to be administered in combination with fludarabine and cyclophosphamide or bendamustine for a maximum of 6 treatment cycles.

Note: 'Chronic lymphocytic leukaemia (CLL)' includes small lymphocytic lymphoma. A line of chemotherapy treatment is considered to comprise a known standard therapeutic chemotherapy regimen and supportive treatments.

Feedback received

We appreciate all of the feedback that we received and acknowledge the time people took to respond. All consultation responses received by 2 June 2017 were considered in their entirety in making a decision on the proposed changes.

Most responses were supportive, and the following issues were raised in relation to specific aspects of the proposal:

Theme Comment
Multiple responders supported the availability of bendamustine and the proposed Special Authority criteria. Noted.
One responder noted that bendamustine is only stable for 24 hours in PVC bags and 48 hours in polyethylene bags (which are not currently widely available in NZ). PHARMAC notes that available stability data is short and careful management and planning will be required to prevent wastage.
Multiple responders noted bendamustine is required twice a week in the first week which will have an impact upon nursing and pharmacy resource.  There will also be an impact on infusion services due to increased survival, but this may be partly offset by less haematological toxicity. Noted.
One responder noted that some of the Special Authority criteria could be simplified with minimal impact on patient numbers treated.  We have considered the proposed amendments but, at this stage, we consider the criteria suitable to target bendamustine to the intended patient groups. We will monitor the operationalisation of the bendamustine criteria and may seek advice on potential amendments at a later stage. 
One responder requested that bendamustine with rituximab may be a good treatment option for CLL patients who relapse within 2 years of FCR chemotherapy.  PHARMAC notes that relapsed CLL is not currently a registered indication for bendamustine in New Zealand, nor have we considered a funding application for its use in this setting. We would welcome a funding application for use of bendamustine in this population. 
One responder noted there are small numbers of patients with iNHL which are CD20 negative (about 2%) and considers bendamustine monotherapy would be an appropriate treatment option, but the criteria as proposed would not allow this.  We have made an amendment to the criteria consulted on to allow bendamustine monotherapy in iNHL patients who are CD20 negative. 
One responder noted that patients may be hospitalised due to lymphoma symptoms and considers this means that a performance status score of 0-2 is overly restrictive. PHARMAC notes that the primary clinical trial evidence for the use of bendamustine in iNHL patients is in patients with ECOG/WHO performance status 0-2. Based on clinical advice from CaTSoP, PHARMAC considers it appropriate to restrict the funding of bendamustine to this group of patients. Should new evidence become available that supports use in those patients with an performance status of 2+, then we could consider an amendment at a later stage.
One responder recommended a change to the proposed new rituximab criteria for CLL to remove the requirement for the patient to have good renal function (creatinine clearance >30 ml/min).  It was noted that while fludarabine cannot be used in patients with a creatinine clearance <30 ml/min, bendamustine can be used in patients with severe renal failure, including in patients on renal replacement therapy. We have amended the criteria consulted on to remove the renal function criterion.

One responder requested that the bendamustine criteria include adequate renal and hepatic function, as per the exclusion criteria used in clinical trials. 

The same responder requested that the rituximab CLL criteria reflect the requirement that bendamustine be used only in patients with a Cumulative Illness Rating Scale (CIRS) score <6.

At its meeting in March 2017, CaTSoP recommended that “GFR >50” be removed from its earlier criteria recommendation for bendamustine for naïve CLL given its minimal renal excretion. PHARMAC notes that mild hepatic dysfunction does not significantly affect the metabolism of bendamustine.

As there is a requirement for the patient to have a CIRS score of <6 in the proposed bendamustine CLL criteria, PHARMAC considers it unnecessary for this to also be included in the rituximab criteria.

More information

If you have any questions about this decision, you can email us at enquiry@pharmac.govt.nz or call our toll free number (9 am to 5 pm, Monday to Friday) on 0800 66 00 50.