Frontline treatment with chemoimmunotherapy for limited-stage ocular adnexal MALT lymphoma with adverse factors: a phase II study

Abstract

BackgroundRadiotherapy is a commonly used treatment for limited-stage ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) but showed a substantial relapse risk if the disease involves beyond-conjunctiva or bilateral conjunctivae. Systemic chemoimmunotherapy may be an alternative frontline therapy for the limited disease with those adverse prognostic factors.Patients and methodsWe designed a multicenter, phase II study of the chemoimmunotherapy, rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) for the treatment of patients with limited-stage OAML with bilateral or beyond-conjunctival involvement. Thirty-three patients with Ann Arbor stage I OAML with the adverse factors were enrolled. Patients received six cycles of R-CVP followed by two cycles of rituximab therapy.ResultsAt the end of treatment, all the enrolled patients had responded. The cumulative complete response achievement was 93.9% at 2 years. At a median follow-up of 50.6 months, three patients had progressed. Progression-free survival and overall survival at 4 years was 90.3±5.3% and 100%, respectively.ConclusionsThis phase II study demonstrated durable efficacy of R-CVP chemoimmunotherapy, which has promise as an alternative frontline therapy for the limited-stage OAML patients with adverse prognostic factors.Clinical trial registrationNCT01427114.

Comparison of Selection and Long-term Clinical Outcomes Between Chemotherapy and Radiotherapy as Primary Therapeutic Modality for Ocular Adnexal MALT Lymphoma

“…Most of our patients presented with locally limited OAML (75.3%), which was limited to conjunctivae and orbital areas, as in most previous studies [3], [19], [25]. Similar to previous reports [9], [16], [24], we found a 7–25% incidence of bilateral ocular adnexal involvement in 23.1% of patients. The association between bilateral involvement and PFS and OS did not have significant statistical power in our large cohort (PFS: HR 1.93, p = 0.124; OS: HR 4.21, p = 0.533), similar to previous studies [30], [38].…”

“…Previously diagnosed autoimmune diseases were found in 10 (4.8%) patients, and these were Hashimoto thyroiditis in seven patients and Sjogren syndrome in three patients (Table 1). We previously reported a phase II study of R-CVP for 33 patients with limited-stage OAML with bilateral or beyond-conjunctival involvement [24]; all of these patients were included in this study as a frontline rituximab-containing chemotherapy group. The basic characteristics of our cohort were substantially different from most Western populations [25], [26], with a younger median age at diagnosis and a low rate of prior diagnosis of autoimmune diseases.…”

Ocular adnexal marginal zone lymphoma (OAMZL)

“…However, definitive data on efficacy of this strategy are still lacking, since most trials are retrospective or considered a group of indolent lymphomas where OAMZLs account only for a minor part of the cohort: the most frequently drugs tested in this setting are chlorambucil, bendamustin (with or without Rituximab), and purine analogs (Sassone et al, 2017). A recent phase II clinical trial with rituximab, cyclophosphamide, vincristine and prednisone (R-CVP) in patients with bilateral, limited-stage OAMZL extending beyondconjunctiva demonstrated a durable response and stressed the possibility and efficacy of a radiationfree upfront approach (93,9% CR at 2 years and 90,3% of PFS at 4 years) with severe side effects (neutropenia and hepatotoxicity) in a minority of cases (12% and 6%, respectively) (Kim et al, 2017). Data on immunotherapy alone are few, mainly focused on larger indolent NHL and extragastric marginal lymphomas categories: a phase II trial in 18 patients with relapsed/refractory extranodal MZL with Lenalidomide monotherapy obtained an ORR of 61% and manageable sideeffects; another study using Bortezomib in patients with newly diagnosed or relapsing/refractory MALT lymphoma showed good efficacy, with an ORR of 80%, but with relevant side effects (Kiesewetter et al, 2013;Troch et al, Hematologica 2009).…”

Organ-specific considerations for marginal zone lymphomas in Korea, based on Consortium for Improving Survival of Lymphoma (CISL) and Korean clinical studies

“…Despite the effective local control of tumor, radiotherapy has the disadvantages of ophthalmologic toxic effects, including late complications such as radiation cataract, xerophthalmia, ischemic retinopathy, glaucoma, and corneal ulceration. In a Korean prospective phase II trial [9], 33 patients with Ann Arbor stage I OA-MZL with the adverse factors were enrolled. They received six cycles of R-CVP followed by two cycles of rituximab therapy.…”