by ecancer reporter Janet Fricker

Initial treatment with rituximab significantly lengthened time to initiation of treatment with chemotherapy for patients with advanced stage follicular lymphoma (FL) compared to patients undergoing watchful waiting, concluded a phase III study presented at the American Society of Haematology (ASH) annual meeting and Exposition held December 4-7, 2010 in Orlando, Florida.

Patients with asymptomatic, advanced stage FL have been found to achieve no benefit from immediate chemotherapy when compared with a watchful waiting approach, leading to the current standard of care where use of chemotherapy is delayed until the cancer progresses. A watchful waiting approach can, on average, defer chemotherapy for 2.5 years and is believed to lead to improved quality of life due to avoidance of the side effects of chemotherapy and a reduction in hospital visits and blood tests. The advent of rituximab, a monoclonal antibody that selectively depletes cancerous B cells and has a more favourable side effect profile than chemotherapy, has led to questions being raised about whether treating asymptomatic FL patients with rituximab might prove beneficial.

The current study by Krit Ardeshna and colleagues from University College London Hospitals (UK) set out to determine whether treating FL patients with rituximab immediately after diagnosis might delay the time until chemotherapy was needed compared with the watchful waiting approach.

Between September 2004 and May 2009, 462 patients with asymptomatic stage 2, 3, or 4 FL were randomised to one of three treatment arms. In arm A, 186 patients underwent a watchful waiting approach; in arm B, 84 patients received 375 mg/m2 of rituximab once a week for four weeks; and in arm C, 192 patients received 375 mg/m2 of rituximab once a week for four weeks followed by rituximab maintenance therapy, given every two months for two years. Because the study was accruing slowly the investigators closed arm B.

Results show that at three years 48% of patients in the watchful waiting arm(arm A) had not required chemotherapy or radiotherapy versus 80% in the rituximab induction arm (arm B) and 91 % in the rituximab maintenance arm (arm C). Additionally, significant differences in progression free survival were found between the observation and rituximab arms (P<0.001) favouring rituximab. For overall survival, however, there was no difference between the three arms, with 95% of patients being alive at three years.

Rituximab was very well tolerated- with seven infections (four of which were grade 3 requiring intravenous antibiotics); five allergic reactions (two of which resulted in bronchospasm); and four cases of neutropenia (only one of which resulted in sepsis).

"This study demonstrates that treating asymptomatic patients with rituximab can significantly prolong the time until a patient may require chemotherapy," said Ardeshna, adding that they have measured the quality of life in the study but have yet to analyse the data.

"Provided the quality of life is no worse in the rituximab arm it's likely that delaying chemotherapy by administering rituximab to asymptomatic patients will become a popular option among doctors for patients with asymptomatic FL and it's likely to become the standard of care."

Whether overall survival would be improved, he added, was currently unclear. "But there are theoretical reasons to think that treating patients upfront would prolong overall survival because patients would not be accumulating genetic lesions that lead to resistance," said Ardeshna.

He added that additional studies will be needed to see how the response to chemotherapy varies between patients who have received rituximab and those who have not.

Reference

K M Ardeshna, P Smith, W Qian et al. An Intergroup randomised trial of rituximab versus a watch and wait strategy in patients with Stage II, III, IV, asymptomatic, non-bulky follicular lymphoma (Grades1, 2 and 3a). A preliminary analysis. Abstract no 6, ASH Symposium 2010.