Sequential radioimmunotherapy with tositumomab/Iodine I131 tositumomab followed by CHOP for mantle cell lymphoma demonstrates RIT can induce molecular remissions

Abstract

7560 Background: Mantle cell lymphoma remains a clinical challenge particularly for pts not candidates for consolidation with ASCT or treatment with leukemia induction regimens. Methods: We investigated sequential radioimmunotherapy (RIT) cytoreduction with tositumomab/Iodine I131 tositumomab followed by CHOP chemotherapy as initial therapy for patients either ineligible for or unwilling to undergo high dose therapy and stem cell transplantation. In addition, pts had to have less than 25% of the intratrabecular bone marrow space involved with lymphoma. Results: Twenty-five patients (pts) were enrolled but only 24 were treated with the therapeutic dose of RIT because a manufacturing problem prevented the treatment of one patient. The median age was 66 (45–80), there were 23 men and 2 women. All patients had advanced stage (III/IV) disease and bone marrow was involved in 48% and the GI tract was involved in 48% of the patients. The overall response rate (ORR) to RIT was 83% (CR/CRu 46%; PR 38%). Two pts withdrew consent following the RIT (and are censored from that point); 1 pt with disease progression requiring alternative therapy is included in EFS and OS analyses. Twenty-one pts proceeded to the CHOP consolidation and 19 completed planned therapy (1 pt died of a CVA; 1 pt chose not to complete chemotherapy after two cycles of CHOP). At the completion of delivered therapy the ORR was 86% (CR/CRu 67%, PR 19%). The median follow up is 2.1 years (0.7 to 4.2). The median EFS was 1.4 years though there have been no events beyond 1.7 years with 7 pts at risk; median OS has not been reached (92% at 2.1 years). Minimal residual disease (MRD) was evaluated with a clonotypic PCR (cPCR) capable of detecting about 1:105 tumor cells; this assay was informative in 17 pts. Following induction with RIT 6 pts (46%) were molecularly negative in blood and bone marrow. Despite the increase in clinical CR following CHOP consolidation, no additional pts became molecularly negative. Conclusions: RIT with tositumomab/iodine I131 tositumomab is a very active agent in the treatment of MCL; unfortunately, MRD is not effectively eliminated by subsequent CHOP chemotherapy. We are planning to explore chemotherapy induction followed by RIT. [Table: see text]