Treating CLL

Traditionally CLL has been considered an incurable disease and short-term responses were considered the best markers of therapy success.

New therapies are now emerging that offer the prospect of long-term remission and consequently the goals of treatment are becoming more ambitious, particularly for physically fit patients who can tolerate aggressive therapy. For example, the treatment algorithm of Balducci and Extermann (2000), states that the treatment approach in CLL should be tailored according to patients’ fitness and degree of comorbidity rather than using age alone as a guide to decision making.

Overall survival is now considered an appropriate endpoint for clinical studies in physically fit patients and extended survival is becoming the primary goal of therapy in routine clinical practice. The duration of response and progression-free survival are similar endpoints and measure the length of time that a patient is kept in remission, but endpoints such as event-free survival and survival duration are also considered appropriate measures of treatment efficacy.

MabThera-based treatment strategies that are available (or are currently being developed) in CLL involve combining this new agent with conventional chemotherapeutics. This approach is based on preclinical data showing that as well as having single-agent activity in CLL, MabThera acts synergistically with chemotherapy. After exposure to MabThera, non-Hodgkins lymphoma (NHL) cell lines became sensitised to the apoptotic effects of many common chemotherapeutics including fludarabine² and in cells from CLL patients, MabThera showed synergy with bendamustine, cladribine, doxorubicin, and mitoxantrone.³

Dose escalation studies have shown that MabThera has dose-dependent activity in CLL and that higher doses are required than in NHL.⁴ As a result, a dose of 500mg/m² was chosen for subsequent clinical trials of MabThera in CLL.

References

1. Hallek M, Cheson BD, Catovsky D, et al. Blood 2008;111:5446–5456.

2. Alas S, Emmanouilides C, Bonavida B. Clin Cancer Res 2001;7:709–723.

3. Chow KU, Sommerlad WD, Boehrer S, et al. Haematologica 2002;87:33–43.

4. O’Brien SM, Kantarijian H, Thomas DA, et al. J Clin Oncol 2001;19:2165–2170.