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Haematological Cancer
Table 2: Response Rates for Front-line Therapy in Chronic
The Place of Alemtuzumab in Current Treatment of
Lymphocytic Leukaemia
Chronic Lymphocytic Leukaemia
Thus, the question arises: where do the CAM307 data and alemtuzumab
Agent OR CR Reference
fit in CLL treatment? Table 2 summarises the published response rates for
Chlorambucil 55% 2% Hillmen, 2007
52
*
those treatments (monotherapy and combinations) in current use for
Alemtuzumab (IV) 83% 24% Hillmen, 2007
52
*
Alemtuzumab (SC) 87% 19% Lundin, 2002
50
first-line treatment of CLL. These data seem to support the use of
Fludarabine 63% 20% Rai, 2000
27 fludarabine-based combination therapy as first-line treatment in younger,
Rituximab 51% 4% Hainsworth, 2003
54
fitter patients. For older patients or those with co-morbidities, who may
Fludarabine + 94% 39% Catovsky, 2007
34
be less able to tolerate such combination regimens, the treatment
cyclophosphamide (FC)
modality is less clear. Chlorambucil may still be an acceptable first-line
FC + mitozantrone 91% 50% Bosch, 2005
31
therapy for this group. The recent UKLRF phase III study demonstrated
Fludarabine + rituximab 90% 47% Byrd, 2003
35
that chlorambucil, fludarabine and FC are not as effective for patients
FC + rituximab 95% 70% Keating, 2005
36
with high-risk genomic features, including those with del(11q22.3) and
*CAM307 phase III prospective randomised trial comparing chlorambucil and alemtuzumab.
del(17p13.1). This suggests that treatments using the p53 pathway for
patients.
52
Patients were randomly assigned to alemtuzumab their activity are not very effective.
34
Therefore, new treatments that are
intravenously (IV) for 12 weeks (n=149) or chlorambucil (n=148). The independent of p53 should be considered for these patients.
ORR for the alemtuzumab group was significantly higher compared with Alemtuzumab alone
42,43
or in combination with high-dose
the chlorambucil group (83 versus 55.4%). Furthermore, alemtuzumab methylprednisolone
53
has been reported to overcome resistance to
was superior to chlorambucil as measured by PFS, with an overall median chemotherapy in a proportion of these patients. These encouraging data
PFS of 14.6 months (95% confidence interval [CI] 12.–21.7 months) for suggest that this monoclonal antibody might find its place as first-line
patients in the alemtuzumab arm and 11.7 months (95% CI 9.9–13.2 therapy for those with p53-associated chemoresistance. The promising
months) for patients in the chlorambucil arm (stratified log-rank efficacy that alemtuzumab has displayed in the CAM307 trial and the
p=0.0001). Median follow-up was 24.5 months for alemtuzumab and better tolerability/toxicity profile seen in the first-line setting may also
24.9 months for chlorambucil. The median time to alternative therapy encourage its use in those patients who may be unable to receive
was 23.3 months for alemtuzumab, with a median 11.7 weeks of conventional chemotherapeutic agents because of co-morbidities.
therapy, and 14.7 months for chlorambucil, with a median 28.3 weeks of
therapy. Thus, alemtuzumab treatment resulted in a treatment-free Summary and Conclusion
period of approximately 88 weeks compared with 36 weeks for The stratification of CLL patients into prognostic groups using new
chlorambucil. The very similar results seen in the study using molecular markers has enabled the application of risk-tailored treatment
subcutaneous alemtuzumab to those seen in CAM307 suggest that this strategies. Additionally, monoclonal antibodies have presented radical and
route of administration may have the same efficacy as intravenous improved treatments for CLL, and several trials continue to explore the full
alemtuzumab and would be easier to manage in the outpatient setting. potential of these agents. In particular, the role of immunotherapy as first-
Also in agreement with the Lundin study,
50
cytomegalovirus (CMV) line therapy in CLL needs to be further defined, together with addressing
events were the most serious alemtuzumab-related adverse effects questions regarding the role of combination treatment and
observed in the study. In patients with symptomatic CMV, ORR was 83% consolidation/maintenance strategies. The recently published CAM307 trial
with 26% complete response, and in patients with asymptomatic CMV shows that the monoclonal antibody alemtuzumab is a highly effective
ORR was 92% with 29% complete response. Median PFS for all PCR- agent suitable for first-line monotherapy of CLL. This may lead to the more
positive CMV patients was 14.6 months, the same as for the entire confident use of alemtuzumab in specific subgroups of patients, such as
treatment arm, and all recovered with antiviral treatment. Other those with TP53 abnormalities, and to further exploration of combination
infections were similar in both arms of the study and there were no regimens. The question of whether the beneficial effect obtained with
treatment-related deaths. monoclonal antibodies translates into a longer survival awaits answers. ■
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52 EUROPEAN ONCOLOGY
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