NICE Gives Green Light To MabThera(R) (Rituximab) For Wider Use In Patients With Most Common Chronic Leukaemia

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Cancer / Oncology;  Regulatory Affairs / Drug Approvals
Article Date: 30 Jul 2010 - 3:00 PDT

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The National Institute for Health and Clinical Excellence (NICE) extended its recommendation for the use of targeted antibody MabThera® (rituximab) to include people with relapsed and difficult-to-treat (refractory) chronic lymphocytic leukaemia (CLL) except where patients have received the full therapeutic dose of MabThera in the first line setting or are refractory to fludarabine. CLL is the most common long-term form of leukaemia in the UK.1 This extension was based on evidence demonstrating that when given in combination with fludarabine and cyclophosphamide (FC) chemotherapy, rituximab extends the length of remission by 10 months2a and almost doubles the likelihood of achieving complete response2b compared to chemotherapy alone.

Dr Claire Dearden, Consultant Haematologist, Royal Marsden Hospital, commented: "When added to chemotherapy, rituximab consistently delivers superior outcomes to chemotherapy alone, putting more patients into longer remissions, the key goal of treatment for chronic leukaemia. NICE's decision to widen its recommendation to include relapsed and refractory CLL patients is very encouraging and will mean that many more people will now be able to benefit from this potent treatment combination."

Findings from the REACH trial, which provided evidence for NICE's recommendation, compared rituximab in combination with fludarabine and cyclophosphamide chemotherapy (known as R-FC) with FC alone, in people who had previously received one prior therapy for CLL and required further treatment. For those in the R-FC arm, progression-free survival was extended by 10 months compared to those given FC alone (30.6 months versus 20.6 months respectively).2a This constituted a nearly 50 per cent improvement for R-FC over FC.2a The proportion of people achieving complete response in the R-FC arm was also nearly double that of the FC arm: 24 per cent versus 13 per cent.2b

In addition to this extension recommendation, NICE is planning to review its guidance in December 2010 to consider rituximab in combination with other suitable chemotherapy drugs for the treatment of CLL, as per its licence. The review will consider new data which show that combining rituximab with another commonly prescribed chemotherapy - chlorambucil - achieves a 17.3 per cent improvement in the overall response rate, compared to a similar patient group on chlormabucil from an earlier key trial.3

Dr Claire Dearden added: "Rituximab is showing promising results in combination with other chemotherapies, and I look forward to the outcome of NICE's review of additional new data in December which I hope will give clinicians greater flexibility in future to prescribe rituximab with other chemotherapy combinations to CLL patients."

Rituximab was granted a licence by the European Medicines Agency (EMEA) in March 2009 for use in previously untreated patients with CLL in combination with any suitable chemotherapy. This licence was extended in September 2009 to include people with relapsed and refractory CLL. The Scottish Medicines Consortium (SMC) issued updated guidance in January 2010 recommending rituximab in combination with any suitable chemotherapy for CLL patients in Scotland on the NHS, in line with rituximab's licence.4

Jane Barnard, Chair of the CLL Support Association, said: "For people with CLL who have relapsed or whose disease has been resistant to other treatments, this is an important breakthrough. New treatments that help to halt disease progression, alleviate debilitating symptoms and give people improved quality of life are essential for this common and potentially devastating blood cancer." FACTS

Please refer to the rituximab Summary of Product Characteristics for full details, available here.

Notes

Full NICE guidance

Rituximab in combination with fludarabine and cyclophosphamide is recommended as a treatment option for people with relapsed or refractory chronic lymphocytic leukaemia except when the condition:

-- is refractory to fludarabine (that is, it has not responded to fludarabine or has relapsed within 6 months of treatment) or

-- has previously been treated with rituximab

- in the context of a clinical trial, at a dose lower than the dose currently licenced for chronic lymphocytic leukaemia or
- in the context of a clinical trial, in combination with chemotherapy other than fludarabine and cyclophosphamide.

About CLL

CLL is a blood cancer caused by the malfunctioning of a type of white blood cell (B-cells or Blymphocytes). Healthy B-cells are involved in fighting infection by producing antibodies. B-cells normally reproduce in a controlled manner, however in CLL the normal function of these cells is compromised, and the damaged B-cells eventually grow out of control. They then outnumber healthy blood cells in the body and prevent them from working normally. CLL leads to the suppression of the immune system, failure of the bone marrow and infiltration of malignant cells into organs. CLL can spread to the lymph nodes, spleen, liver, central nervous system and other organs. It does not usually form a solid mass or tumour.9

About rituximab (MabThera®)

Rituximab is a monoclonal antibody (sometimes shortened to 'mAb'), a type of man-made molecule that targets specific cells, or parts of cells, for destruction. Rituximab binds to a particular protein, the CD20 antigen, which is expressed on the surface of normal and malignant mature B-cells, a type of white blood cell vital to the body's immune system. Disruption to the normal function of B-cells is a hallmark of many diseases, including non-Hodgkin lymphoma, rheumatoid arthritis and CLL. The way in which rituximab targets B-cells means it is capable of tackling more than one disease. Rituximab is licensed in chronic lymphocytic leukaemia, certain types of non-Hodgkin lymphoma and rheumatoid arthritis.

Rituximab in CLL timeline

March 2009 - First-line licence granted in combination with any chemotherapy

June 2009 - SMC recommends rituximab for first-line use in combination with FC chemotherapy

July 2009 - NICE recommends rituximab as an option for first-line use in combination with FC Chemotherapy

September 2009 - Relapsed/refractory licence granted in combination with any chemotherapy

January 2010 - SMC extends use of rituximab to include patients with CLL (first-line and relapsed/refractory) in combination with any chemotherapy

July 2010 - NICE extends recommendation for rituximab as an option for relapsed/refractory patients in combination with FC chemotherapy

About the REACH trial

REACH was an open-label, multi-centre, multinational randomised phase III study of 552 patients with relapsed/refractory CLL. The trial was designed to evaluate the efficacy and tolerability of R-FC versus FC. The primary end-point was progression-free survival. The lead investigator was Professor Tadeusz Robak, Medical University, Lodz, Poland.

References

1. Cancer Research UK: Last accessed July 2010.

2. Robak, T. et al. (2008) Rituximab plus Fludarabine and Cyclophosphamide (R-FC) vs. FC alone in Relapsed/Refractory CLL: Final Results of the REACH BO17072 trial. Abstract presented at the 50th ASH Annual Meeting and Exposition, December 6-9, 2008, San Francisco, USA.

3. Hillmen, P. et al. (2009) 'An Open-Label Phase II Study to Investigate the Safety and Efficacy of Rituximab Plus Chlorambucil In Previously Untreated Patients with CD20-Positive B-Cell Chronic Lymphocytic Leukaemia (CLL)'. Abstract presented at the 51th ASH Annual Meeting and Exposition, December 5-8, 2009, New Orleans, USA.

4. Scottish Medicines Consortium MabThera Assessment, January 2010 (no. 591/09).

5. 'Chronic lymphocytic leukaemia', G Dighiero, T J Hamblin, Lancet 2008; 371: 1017-2975.

6. Figure has been calculated by applying the 2007 Scottish prevalence rates per 100,000 to the 2007 UK population (61m)

7. Office for National Statistics Last accessed July 2010.

8. Leukaemia and Lymphoma Research Last accessed July 2010.

9. CLL Support Association

Source:
Roche

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