Oral Arsenic Trioxide Based Regimen As Salvage Treatment For Relapsed Or Refractory Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoproliferative disorder, and relapsed/refractory disease has a poor prognosis. In patients with relapsed / refractory MCL, optimal treatment strategy remains undefined. Oral arsenic trioxide (As₂O₃) was initially developed for the treatment of relapsed acute promyelocytic leukemia (APL). As₂O₃ inhibits neoplastic cellular proliferation by a wide array of mechanisms, including induction of apoptosis, targeting of signaling pathways, and down-regulation of BCL-2. Evidence in vitro also suggested that As₂O₃ might be effective in lymphoma, but clinical data are hitherto not available. In this study, we investigated the use of an oral-As₂O₃-based regimen for the treatment of patients with relapsed / refractory MCL. Thirty-nine patients (men=34, women=5) at 64 (41–82) years of age with relapsed/refractory MCL, who had received 2 (1–5) prior regimens and were ineligible for high-dose chemotherapy, were treated with a continuous oral regimen, comprising oral arsenic trioxide (oral-As₂O₃), chlorambucil and ascorbic acid. The overall response rate was 49% (complete response: 28%; partial response: 21%). Only grade 1/2 toxicities were observed (hematologic: 56%, hepatic: 8%). Independent prognostic factors for response were increased lactate dehydrogenase (P=0.04) and unfavorable MCL international prognostic index (P=0.04). At a median follow up of 21(range:1-118) months, the median progression-free-survival (PFS) was 16 months, and overall-survival (OS) 38 months. The 2-year and 5-year PFS were 41% and 29% respectively. The 2-year and 5-year OS were 56% and 43% respectively. Independent prognostic factors for PFS were female gender (P=0.002), Eastern Cooperative Oncology Group (ECOG) performance score of 2 (P=0.009), and non-response to treatment (P<0.001). Independent prognostic factors for OS were female gender (P<0.001), ECOG performance score of 2 (P=0.03), non-response to treatment (P<0.001), and disease progression while on treatment (P=0.05). These findings showed that an oral regimen of oral-As₂O₃, chlorambucil and ascorbic acid was an active regimen with minimal toxicity in relapsed/refractory MCL, achieving durable responses in some cases.