Rituximab Maintenance Therapy Is an Effective Therapy in over-Sixties with Mantle Cell Lymphoma

Abstract

Introduction Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma (NHL) accounting for 5 percent of NHLs. Most patients with MCL are 60 years of age and older. The prognosis of patients with MCL is moderately aggressive and variable; the median overall survival is 3-5years. MCL international prognostic index(MIPI)is related to prognosis of the patients with MCL, however, it is unclear whether MIPI predicts outcomes of MCL over sixties. Out therapeutic strategy in elderly patients with newly diagnostic MCL is not high-dose chemotherapy with autologous stem cell transplantation. Instead of aggressive chemotherapy, Rituximab maintenance is considered as an effective and feasible option. Thus, we investigated whether MCL international prognostic index (MIPI) relates overall survival (OS) or progression free survival (PFS), and whether maintenance therapy with Rituximab improved OS or PFS in patients with newly diagnosed MCL patients 60 and older. Methods We analyzed retrospectively 60 years of age and older patients with MCL who have achieved complete response (CR) or partial response (PR) after induction chemotherapy with rituximab at our hospital from December 2005 to February 2015. Two of primary refractory patients were excluded because analysis is for patients who are eligible for rituximab maintenance therapy. The patients were diagnosed by hematopathologist in our hospital. According to the MIPI, patients were stratified into low risk (0 patients, 0%), intermediate risk (9 patients, 41%), and high risk (13 patients, 59 %). Induction chemotherapy regimens were six cycles of R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone), four cycle of R-hyper CVAD/MA (rituximab-cyclophosphamide-vincristine-doxorubicin-dexamethasone alternating with rituximab-methotrexate-cytarabine), six cycles of R-CVP (rituximab- cyclophosphamide-vincristine-predonisone), R-VP16 (rituximab-etoposide), or six cycles of VR-CAP (bortezomib-rituximab-cyclophosphamide-doxorubicin- predonisone). Rituximab maintenance therapy started 6 months after the last induction chemotherapy and underwent four weekly infusion every 6 months for 2 years. Results A total of 22 MCL patients were analyzed. The number of patients who had achieved CR was 14 and PR was 8. 14 of 22 patients were treated rituximab maintenance. Median age was 73 years old. MIPI could predict OS of MCL. 3-year-OS was significantly superior intermediate risk to MIPI high risk (3-years-OS: 87.5 %vs.51.9 %,p=0.0232), whereas PFS didn't have correlation with MIPI(3-years PFS70.0 %vs.38.5 %,p=0.136). 3-years OS was significantly superior maintenance group to no maintenance group (3-years survival rate 91.7 % vs. 25.0 %, p=0.00188, figure 1), and 3-years PFS tend to improve in the maintenance group (3-years PFS, 65.8 % vs.25.0 %, p=0.0773, figure 2). Conclusion: In this study, MIPI correlates with OS, however doesn't show with PFS. Rituximab maintenance therapy is effective, and prolongs OS for 60 years of age and older patients with MCL. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Nishimura: Chugai Pharmaceutical CO., LTD.: Consultancy. Mishima:Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.

The B cell receptor signaling pathway in mantle cell lymphoma

“…In young newly diagnosed patients, treatment often takes the form of high dose chemotherapy in combination with rituximab, followed by autologous stem cell transplant (ASCT). In older patients, rituximab has demonstrated efficacy as maintenance therapy after induction chemotherapy (often CHOP or CVP) [ 46 ]. Results from a recent international phase III trial indicate that rituximab maintenance may be useful in young patients after ASCT as well, with 4-year overall survival of 78% [ 47 ].…”

Past, Present, and Future of Rituximab—The World’s First Oncology Monoclonal Antibody Therapy

“…Diffuse large B-cell lymphoma is the most common type of NHL, representing 30–40% of all lymphoma diagnoses in Western countries ( 17 , 18 ). Since the World Health Organization’s (WHO’s) consensus in 2008, DLBCL has been categorized as germinal center B-cell-like (GCB), activated B-cell-like (ABC), or as unclassifiable lesions which do not fit either profile ( 19 ).…”

“…The first phase II single-arm trial for treating DLBCL with rituximab was reported in 2001, studying patients who had aggressive, untreated NHL. Thirty-three patients were included in this trial; the majority of patients (67%) had DLBCL ( 17 ). The study showed a 94% overall response rate (ORR) compared with historical CHOP controls (80–90%) and 61% CR compared with historical CHOP controls (44–55%), with only two patients experiencing disease progression by week 24 ( 21 ).…”

“…Burkitt lymphoma accounts for 1–5% of adult NHL and is characterized as aggressive lymphoma that is associated with extremely short doubling time caused by MYC dysregulation ( 17 ). The disease is usually treated with short-intensive regimens of high-dose cyclophosphamide and methotrexate in combination with vincristine, doxorubicin, and cytarabine, and this has achieved high cure rates in pediatric BL, but a less ideal OS of 64% in adults with the disease ( 30 ).…”

“…Mantle cell lymphoma is a moderately aggressive lymphoma that comprises 2–4% of all NHL and has a median OS of 3–5 years ( 17 ). MCL is technically classified as an indolent lymphoma; but it usually has an aggressive clinical course and is incurable, despite an initial response to either dose-intense chemotherapy or combination therapy ( 34 ).…”