A new less toxic treatment, combining the chemotherapy drug fludarabine with the monoclonal antibody alemtuzumab significantly increases progression free survival (PFS) and prolongs the lives of patients who have relapsed with the most common type of leukaemia, chronic lymphocytic leukaemia (CLL), compared with fludarabine alone. The findings, published in The Lancet Oncology, suggest that this new drug combination could be an important additional treatment for patients with this incurable disease.

"Unlike common regimens used to treat CLL, the new two-drug combination spares patients from the toxicities of additional alkylating drugs. Moreover, the required dose of each drug is lower when used in combination than when the drugs are used alone, and the dosing schedule of 3 days a month is more convenient for patients than the standard regimen of three times a week for up to 12 weeks", explains lead author Thomas Elter from the University of Cologne, Cologne, Germany.

The substantial diversity of patients with CLL in terms of disease burden, age, and co-occurring illnesses means that there is no one standard treatment for all patients with CLL, and several additional treatment options need to be available.

The phase 3 trial randomly assigned CLL patients from centres across North America and Europe to either fludarabine plus alemtuzumab (168 patients) or fludarabine alone (167) for a maximum of six 28-day cycles.

The researchers found that both PFS (23.7months vs 16.5 months) and overall survival were significantly better with the combination treatment than with fludarabine alone. Complete response rates were also much improved with the fludarabine plus alemtuzumab combination.

Importantly, even older patients and those with advanced disease benefited from the new combination regimen.

Overall, both treatment groups experienced a similar number and severity of infectious complications. Both groups had a similar frequency of grade 3 or 4 neutropenia (low white blood cell count) and thrombocytopenia (abnormally low number of blood platelets), but anaemia was lower in the combination group (9% vs 17%), whilst lymphopenia (abnormally low number of lyphocytes in the blood: 94% vs 33%) was more common.

Although the incidence of serious adverse events was higher in the combination group (33% vs 25%), the number of patients who discontinued treatment and deaths during treatment was similar in both groups.

The authors conclude: "The combination of fludarabine and alemtuzumab is another treatment option for patients with previously treated CLL."

Source: The Lancet