Groundbreaking data presented today at the American
Society of Hematology (ASH) annual meeting demonstrate that the addition of MabThera® (rituximab)
to chemotherapy in previously untreated patients with chronic lymphocytic leukaemia (CLL)
significantly improves chances of survival.1 This is the first time that any treatment for CLL, the most
common leukaemia in the UK,2,3,4 has been shown to extend life in a randomised clinical trial1.
The
same trial showed that the addition of rituximab to chemotherapy doubles the number of patients
achieving complete remission and lengthens the period of time before the disease returns by more than
1.5 years, compared to chemotherapy alone.1
Professor Peter Hillmen, Consultant Haematologist, Leeds Teaching Hospitals NHS Trust, commented:
"These results are extremely significant. Never before have we seen proof that any treatment has led
directly to improved overall survival in CLL. The combination of rituximab and fludarabine-based
chemotherapy has proven to be a formidable partnership, sending more patients into remission,
extending the period before their leukaemia returns and now increasing the length of time people
survive overall. This is certainly one of the most significant steps forward we have seen in this area for a
long time."
In the pivotal CLL8 clinical trial, the overall survival rate (the number of people still living) after an
average observation time of 37.7 months was 84.1 per cent in the rituximab plus fludarabine
cyclophosphamide (R-FC) arm versus 79 per cent in the FC arm (p=0.01), showing a statistically
significant increase of 5.1 per cent. In addition, R-FC induced a higher overall response rate (numbers
of people achieving any kind of remission) than FC (95.1 per cent versus 88.4 per cent respectively), and
more than doubled the number of patients achieving complete remission, where no detectable trace of
the disease remains (44.1 per cent R-FC versus 21.8 per cent FC). R-FC also extended progression-free
survival by an extra 19 months compared to FC alone (51.8 months R-FC versus 32.8 months FC). 1
In a separate UK-only study, CLL208, also presented at ASH, rituximab was trialled in combination
with chlorambucil chemotherapy in previously untreated CLL patients. Chlorambucil is the first-line
treatment option of choice for patients who cannot tolerate a more intensive treatment regimen,
typically elderly patients or those with other existing health problems. The interim results from this
study indicate that adding rituximab to this commonly used chemotherapy improves the overall
response rate by 17.3 per cent compared to historical data from patients in another UK study (CLL4)
who received chlorambucil alone. 5
Professor Hillmen, who is lead investigator for the CLL208 trial, explained: "Rituximab's capabilities in
combination with FC chemotherapy have been well proven, however this trial examined its interaction
with chlorambucil, which is the standard treatment prescribed for frailer patients with CLL. The
interim results are very encouraging, showing a significant increase in the overall response rate. With
further analysis this could potentially offer this patient group - up to half of all CLL patients - the
chance to benefit from the increased efficacy rituximab has shown with other chemotherapy
combinations."
Rituximab is licensed to treat all patients with CLL who require treatment in combination with any
appropriate chemotherapy. It has received positive recommendations from the National Institute for
Health and Clinical Excellence (NICE) and Scottish Medicines Consortium (SMC) for first-line use in
combination with FC chemotherapy and is currently undergoing appraisal with both institutions for its
extended licence in relapsed and refractory CLL patients.
Jane Barnard, Chair of the CLL Support Association, commented: "This year has been exceptional in
terms of advances in treatment for people with CLL. The fact that we are now at a stage where we can
see improved overall survival is incredible and this news offers real hope to the many thousands of
people living with this condition in the UK. Extending someone's life, by any amount of time, so that
they are able to spend precious moments with their loved ones, is invaluable."
In the CLL8 trial more hematologic adverse events, particularly neutropenia, were observed with the
FCR treatment, however this did not result in an increased infection rate.1 In the CLL208 trial the most
common adverse events were gastrointestinal disorders and, less commonly, infections. 5
About CLL
Chronic lymphocytic leukaemia (CLL) is a blood cancer caused by a type of abnormal white blood cell
(B-cells). Healthy B-cells are involved in fighting infection by producing antibodies. 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. 2 Further information in the CLL backgrounder
(COMM00333a).
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.
References:
1Hallek, M. et al. (2009) 'First-Line Treatment with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Improves Overall
Survival (OS) in Previously Untreated Patients (pts) with Advanced Chronic Lymphocytic Leukamia (CLL): Results of a Randomized Phase III
Trial On Behalf of An International Group of Investigators and the German CLL Study Group'. Abstract presented at the 51th ASH Annual
Meeting and Exposition, December 5-8, 2009, New Orleans, USA.
2CLL Support Association: cllsupport/aboutcll.htm [accessed November 2009].
3 Cancer Research UK: cancerhelp/help/default.asp?page=17964 [accessed November 2009].
4 Byrd JC et al. 'Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic,
untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712)', Blood 2003;
101: 6-14
5 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.
Source
Roche