Newer Agents

Bortezomib is a potent and specific proteosome inhibitor that down regulates the NF-kB pathway. Recently, two studies have reported encouraging activity with this agent in patients with relapsed/refractory MCL.84 85 Fifty-three percent of patients (8/15) had a response, with a median duration of 3 months. One relapsed MCL patient was retreated and achieved a second PR lasting 4+ months.85 The mechanism of antitumor activity in MCL is not known, though the biology of MCL provides some clues. Reduced expression of P27 and loss of normal P53 function are both associated with a poor prognosis in MCL. The intracellular levels of P27 and P53 are both modulated by proteoso-mal degradation86 87 It is possible that inhibition of the proteosome by bortezomib may contribute to its activity in MCL.

Thalidomide in combination with rituximab was evaluated in relapsed/refractory MCL patients, and impressive antitumor activity has been reported.8889 In one study, 16 patients with relapsed/refractory MCL were treated with rituximab at 375 mg/m2 for four weekly doses concomitantly with thalidomide. Eighty-one percent (13/16) experienced an objective response with 5 achieving a CR (31%). The median PFS was 20.4 months (95% CI, 17.3-23.6), and estimated 3-year survival was 75%.88 There were three severe adverse events: two thromboembolic and one grade IV neutropenia. The encouraging antitumor effect warrants further investigation in MCL.

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