Bendamustine is an alkylating antitumour agent, which acts by crosslinking of DNA single and double strands by alkylation in both quiescent and dividing cells. It is primarily metabolised by hydrolysis in the liver.
There have been two major randomised studies comparing bendamustine-rituximab with CVP/CHOP-R chemotherapyrr in patients with untreated low grade lymphoma or mantle cell lymphoma. The inclusion criteria were similar in both studies. Low grade lymphoma included follicular lymphoma (grade 1 or 2), lymphoplasmacytic lymphoma, splenic marginal zone B-cell lymphoma, extra nodal marginal zone lymphoma of mucosa-associated lymphoid tissue type, nodal marginal zone B-cell lymphoma. Both studies had "need for treatment" criteria, though these differed slightly. In the Rummel study, MCL patients less than 65 were offered enrolment in other trials. Both studies had similar bendamustine schedules, while in the Flinn 2014 study, individual centers chose either R-CVP or R-CHOP as the comparator arm.
The relevant results from each study are summarized in the table below. In the Rummel 2013 study, the Bendamustine arm produced superior response rates, while in the Flinn 2014 Bendamustine was non-inferior. The Rummel 2013 study reported that overall survival did NOT differ between the groups at a median time of analysis of 45 months. This study also indicated superior PFS in bendamustine treated MCL patients of 35.4 versus 22.1 months (p<0.0044).
||Previously untreated stage 3 or 4 low grade or mantle cell lymphoma requiring treatment
||Previously untreated stage 2 to 4 low grade or mantle cell lymphoma requiring treatment
The Rummel 2013 study reported bendamustine to be better tolerated than R-CHOP (see tables below). There were lower rates of alopecia (0% vs 100%; p<0.0001), haematological toxicity (30% vs 68%; p<0.0001), infections (37% vs 50%; p=0.0025), peripheral neuropathy (7% vs 29%; p<0.0001) and stomatitis (6% vs 19%; p<0.0001). Bendamustine was associated with more erythematous skin reactions (16% vs 23% p=0.024).r
© The Lancet 2013
© The Lancet 2013