Ibritumomab Radioimmunotherapy in Mantle Cell Lymphoma

European Oncological Disease, 2007;1(1):76-9 DOI: http://doi.org/10.17925/EOH.2007.0.1.76


General Considerations
It is difficult to establish the true incidence of mantle cell lymphoma (MCL), as there is an important difference between national lymphoma registers (2–4% of non-Hodgkin’s lymphomas, NHL) and reports from reference centres (7–11%).1,2 It may either reflect the diagnostic problems, where MCL is not properly diagnosed and reported as chronic lymphocytic leukemia (CLL) or clustering of the refractory/relapsing patients in the reference centres. The MCL diagnosis must therefore include flow cytometry (CD5+/CD19+/CD20+/CD23-), immunohistochemistry for cyclin D1 and cytogenetic analysis, in case of any doubts. The majority of patients are elderly males over 60 years of age. Prognosis of MCL lymphoma treated with conventional cytoxan, hydroxyrubicin, oncovin, prednisone (CHOP)-like chemotherapy regimens is unsatisfactory: most cases relapse and become resistant to treatment relatively early, with the average progression-free survival (PFS) and overall survival (OS) less than one and three years, respectively.3

Chemoimmunotherapy with Rituximab as an Initial Cytoreductive Regimen
Chemoimmunotherapy is a widely accepted first-line approach as rituximab increases response rate (RR) and prolongs PFS. In a German lymphoma study group (LSG) randomised comparison of CHOP with CHOP-R (with rituximab), CHOP-R increased RR from 72 to 92%, CR from 9 to 32% and PFS from 14 to 21 months, although still without a clear OS benefit.4 Although the addition of rituximab to the fludarabine, cyclophosphamide, mitoxantrone regimen (FCM-R) was superior to FCM in relapsed patients, most of the responses were shorter than 12 months.5 A standard-dose chemoimmunotherapy is just not enough to cure MCL, and some kind of post-induction or consolidation treatment is necessary. For maximum effectiveness, whatever we offer to our patients should be incorporated into the first-line approach, before the resistance occurs. Most of MCL patients are either ‘young’ elderly patients or ‘elderly’ elderly patients. In the first group, an intensive therapy approach with subsequent transplant procedure is the treatment of choice.

Dose Escalation for ‘Fit’ Patients
Autologous transplants as consolidation of the first-line therapy became a gold standard after the first generation of European MCL Network trials demonstrated a PFS benefit compared with INF maintenance (medium PFS 39 months versus 17 months, p=0.01).6 In the ongoing secondgeneration trial, the role of the more intensive induction therapy is investigated, comparing CHOP-R with alternative CHOP-R/DHAP-R. High efficiency (PFS >70% at three years) of chemoimmunotherapy regimens containing intermediate-dose cytarabine was shown in phase II studies: alternative HyperCVAD-R/MA-R regimen developed in MD Anderson,7 alternative MaxiCHOP-R/cytarabine-R followed by BEAM conditioned transplant investigated by Nordic MCL Group8 and Milano high-dose sequential chemotherapy.9 The results of the Nordic and Italian groups are particularly interesting, as they were both performed in a multicentre setting and there is a plateau of OS curves after the third year. Present Nordic Group protocol includes radioimmunotherapy (Z-BEAM) in a transplant-conditioning regimen for partial responders.