Impressive new data presented today from two landmark studies show that a new 'immunochemotherapy' treatment combination allows people with the most common form of leukaemia(1,2,3) to almost double their chance of achieving a complete remission*, compared to those treated with chemotherapy alone(4,5). One study of 817 previously untreated CLL patients (CLL-8 trial) showed that adding the targeted cancer treatment rituximab (MabThera) to chemotherapy (a combination known as R-FC) meant they were almost twice as likely to achieve complete remission compared to those treated with chemotherapy (FC) alone (52% vs. 27%)(4).

In a separate study (REACH), the same immunochemotherapy combination was shown to stop the disease in its tracks in relapsed patients for an additional 10 months when compared to FC chemotherapy alone(5). In this study, complete remission rates were also nearly doubled in the R-FC arm: 24 per cent versus 13 per cent of those given FC alone(5). Results from both studies are being announced today at the American Society of Haematology (ASH) Annual Meeting in San Francisco.

Professor Andrew Pettitt, Consultant Haematologist at Royal Liverpool University Hospital and a UK investigator in the REACH study said: "These results represent a significant advance, and will change the way we approach the treatment of CLL. The goals of treatment are to shrink the disease to the point where we cannot detect it, and to maximise the length of time before the cancer returns.

"The new rituximab-led immunochemotherapy will give many patients the opportunity of living longer without their disease progressing, and many of these will have no signs or symptoms for an extended period of time," Professor Pettitt said.

This research suggests that, in many cases, immunochemotherapy is likely to become the new standard first-(4) and second-line(5) treatment for fit CLL patients.

CLL is the most common form of leukaemia(1,2,3) and there are an estimated 3,400 new cases each year(6). The disease is twice as common in men as in women, with incidence rapidly increasing after the age of 50 years(6).

Professor Andrew Pettitt commented further: "The addition of rituximab to FC chemotherapy delivers deeper, longer-lasting remission for CLL patients who have experienced relapse. When treated with the new combination, patients potentially will remain progression free by almost a year longer than if they had been given FC alone."

First-line treatment with rituximab plus FC chemotherapy almost doubles remission numbers and prolongs progression-free survival compared to chemotherapy alone

The landmark CLL-8 trial showed that 52 per cent of patients in the R-FC arm achieved a complete response (complete remission) versus 27 per cent of patients in the FC arm4. Progression-free survival was significantly improved in the R-FC arm: 76.6 per cent of patients showed no signs that their disease had progressed two years into the trial, compared to 62.3 per cent given FC only(4).

Relapsed patients

The REACH trial compared R-FC with FC, in people with CLL who had had one course of chemotherapy previously and who required further treatment. Those in the R-FC arm extended their progression-free survival by 10 months compared with those given FC (30.6 months versus 20.6 months respectively)(5). This constituted a 50 per cent improvement for R-FC compared to FC. Complete remission rates were also nearly doubled in the R-FC arm: 24 per cent versus 13 per cent of those given FC alone(5).

Tolerability

In the REACH trial, the adverse events seen were very similar between both arms, with low white cell count and infections being the main events seen5. In the CLL-8 trial, adding rituximab to FC led to a significantly higher incidence of a low white cell count (which raises susceptibility to infection), but this susceptibility did not lead to a marked difference in infections between the two types of treatment(4).

Rituximab is not currently licensed for the treatment of CLL

A European marketing licence application was filed for rituximab for previously untreated patients with CLL in July 2008. If the licence application is successful, rituximab should be available for this group of UK CLL patients in the first half of 2009.

Notes

* Complete remission means that all signs of the disease are clinically undetectable, although a few cancer cells may remain in the body.

About chronic lymphocytic leukaemia (CLL)(2)

Chronic Lymphocytic Leukaemia (CLL) is a slowly progressive form of cancer, characterised by an increased number of B lymphocytes, a type of white blood cell that is involved in fighting infection. Blood cells are normally produced in a controlled way, but in CLL the process gets out of control. The lymphocytes multiply too quickly and live too long, so there are too many of them circulating in the blood. These leukaemia lymphocytes look normal, but are in fact not properly developed and do not work properly. Over a period of time the abnormal cells replace the normal white cells, red cells and platelets in the bone marrow. It is the most prevalent form of leukaemia and occurs predominantly in patients over 55 years.

About MabThera (rituximab)(7)

Non-Hodgkin lymphoma (NHL)

Rituximab is currently approved for first-line use for patients with advanced follicular NHL in combination with the chemotherapy, in patients with follicular lymphoma who are resistant to chemotherapy or in second or subsequent relapse. It is also approved for use as maintenance treatment in patients with relapsed or refractory follicular lymphoma who have responded to re-induction therapy and in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy for patients with diffuse large B-cell NHL.

Rituximab works to tackle CLL through three distinct modes of action:

1. Complement-dependent cytotoxicty (CDC): Where rituximab binds to CD20, activating a large protein complex. This results in the formation of holes in the B-cell membrane, flooding the cell, which leads to death

2. Antibody-dependent cell mediated cytotoxicty (ADCC): Where rituximab binds to CD20 and recruits cells that defend the body in an immune response. These cells in turn engulf the bound B- cell and destroy it

3. Apoptosis: Where the binding of rituximab to the B-cells signals the malignant cells to self-destruct

About CLL-8

CLL-8 was a multi-centre, multinational, randomised phase III trial of 817 patients with CLL who needed treatment for the first time. The trial was designed to evaluate the efficacy and tolerability of R- FC versus FC for initial treatment.

About REACH

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.

About Roche in the UK

Roche aims to improve people's health and quality of life with innovative products and services for the early detection, prevention, diagnosis and treatment of disease. Part of one of t he world's leading healthcare groups, Roche in the UK employs nearly 2,000 people in pharmaceuticals and diagnostics.

Globally Roche is the leader in diagnostics, and a major supplier of medicines for the treatment of cancer, transplantation, virology, bone and rheumatology, obesity and renal anaemia. Find out more at rocheuk.

A summary of product characteristics is available at rocheuk.

References

1. cancerbackup/Cancertype/Leukaemiachroniclymphocytic/General/WhatisCLL; accessed 2 December 2008

2. cllsupport/aboutcll.htm; accessed 2 December 2008

3. cancerhelp/help/default.asp?page=17964; accessed 2 December 2008

4. 'Chemoimmunotherapy with Fludarabine (F), Cyclophosphamide (C) and Rituximab (R) (FCR) versus Fludarabine and Cyclophosphamide (FC) improves response rates and progression-free survival (PFS) in previously untreated patients (pts) with advanced lymphocytic leukaemia (CLL)', Hallek M. et al, abstract presented at the 50th ASH Annual Meeting and Exposition, December 6-9, 2008, San Francisco CA

5. 'Rituximab, Fludarabine and Cyclophosphamide (R-FC) prolongs progression free survival in relapsed or refactory chronic lymphocytic leukaemia (CLL) compared with FC alone: Final results from the International Randomized Phase III REACH Trial', Tadeusz Robak et al, abstract presented at the 50th ASH Annual Meeting and Exposition, December 6-9, 2008, San Francisco CA

6. Chronic lymphocytic leukaemia, G Dighiero, T J Hamblin, Lancet 2008; 371: 1017-2975 cllsupport/aboutcll.htm

7. Rituximab summary of product characteristics

Source:
Louise Pontifex
Roche