Should There Be a Standard Therapy for Mantle Cell Lymphoma?

Mitchell R Smith

Disclosures

Future Oncol. 2011;7(2):227-237. 

In This Article

Consolidation of Remission

In older patients, the risks of high-dose chemotherapy with stem cell support increase. Less intensive consolidation approaches may be better. While rituximab maintenance is becoming increasingly accepted in indolent lymphoma, at least to prolong PFS, less is known about the value of rituximab maintenance therapy in MCL. Rituximab maintenance did significantly prolong PFS in one study after fludarabine, cyclophosphamide and mitoxantrone chemotherapy,[51] so rituximab maintenance has been included in many recent studies to try and prolong the disease-free interval. Pharmacokinetic data have suggested that a single dose of rituximab administered every 3 months would maintain effective blood levels in most patients; however, pharmacokinetic data from the Rituximab Extended Schedule or Retreatment Trial (RESORT) trial in indolent lymphoma patients with low tumor burden indicated that rituximab may need to be administered every 2 months to maintain adequate levels in many patients.[52] An every-2-month schedule has been used in several trials,[53] including most recently the Primary Rituximab and Maintenance (PRIMA) trial. Rituximab maintenance in MCL currently remains investigational, but its role should be defined by data, expected in mid-2011, from the European randomized Phase III study of rituximab maintenance versus observation following either R-CHOP or R-fludarabine-based induction therapy.

Lenalidomide is an immunomodulatory agent whose precise mechanism of activity remains unclear. It has activity in both indolent and aggressive lymphoma and CLL. Some patients with relapsed/refractory MCL were included in earlier lenalidomide lymphoma trials and showed response rates of 53%.[54] The fact that lenalidomide can activate ADCC, enhancing rituximab cytotoxicity, provides the preclinical rationale for the combination of rituximab and lenalidomide.[55,56] High response rates of the combination of lenalidomide and rituximab are suggestive of possible synergy in relapsed CLL, as well as in front-line and relapsed indolent lymphoma. Increasing experience with prolonged lenalidomide administration in myeloma indicates its safety and tolerability. Consolidation therapy with lenalidomide significantly prolongs remission duration in myeloma following chemotherapy or SCT. Possible strategies to build on these data in MCL include the use of the lenalidomide plus rituximab combination as initial therapy or use as consolidation.

Radioimmunotherapy is active in refractory MCL, but with short response durations. Used as up-front therapy, RIT demonstrated high RR, but again with a short duration.[57] RIT consolidation in first remission, as previously discussed,[41] improved responses and had an encouraging median PFS of 27 months, although with no plateau in PFS curves.

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