An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma

Abstract

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range 21 to 85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (n=228, 96.2%), stage III/IV (n=179, 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range 1 to 8) cycles of BR, and 20.3% (n=48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy. Herpes-zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95%CI 73.1-86%) and 89.6% (95%CI 83.1-93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (HR=0.16, 95%CI 0.04-0.71; P=0.016) but did not impact OS. BR is a highly effective upfront regimen in EMZL providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes-zoster and thus prophylactic treatment may be considered.

Bendamustine and rituximab is well‐tolerated and efficient in the treatment of indolent non‐Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study

“…In 235 patients with Waldenstroem's Macroglobulinemia treated with BR induction, 89.9% of patients achieved a PR 21 . Treatment with BR demonstrated excellent efficacy in our MZL patients with 100% ORR, similar to the previously reported rate between 89.3 to 100% 19,22 . CR rate was similar for elderly and younger patients.…”

“…The proportion of patients who experienced fatigue was not increased in the elderly group. The rate of infections in our patients was similar to the one reported in STiL and BRIGHT trials but was higher than in a recent multicenter report of BR in extranodal MZL where 13% of patients experienced infectious complications during BR therapy, including herpes zoster reactivation in 4% of patients 19 . In our patients, herpes zoster reactivation was significantly higher in the elderly cohort; thus, we now introduced prophylactic treatment with valacyclovir at our institution.…”

“…21 Treatment with BR demonstrated excellent efficacy in our MZL patients with 100% ORR, similar to the previously reported rate between 89.3 to 100%. 19,22 CR rate was similar for elderly and younger patients. Similar to MZL, ORR for MCL was over 95% in both elderly and younger patients.…”

Management of Extranodal Marginal Zone Lymphoma: Present and Upcoming Perspectives

“…Lymphopenia was the most frequently observed adverse event [ 112 ]. Further studies have confirmed these findings [ 113 , 114 , 115 ], also in pretreated patients [ 116 ]. Of note, one large study of an international consortium with 237 EMZL patients showed an ORR of 93.2% and a CR rate of 80%.…”

“…Patients received a median of six cycles (range 1–8). Importantly, treatment with bendamustine is related to prolonged lymphopenia and risk of infections; Herpes zoster was frequently observed in patients treated with this regimen, and therefore, an adequate prophylaxis might be needed until immune reconstitution [ 114 ].…”