Frontline bendamustine and rituximab (BR) produced durable responses in patients with extranodal marginal zone lymphoma (EMZL), according to research published in Blood Advances.

Researchers evaluated the safety and efficacy of frontline BR in EMZL using a large international consortium of 20 institutions from Italy and the United States.

The study included 237 patients treated with frontline BR from January 2008 to February 2022. The patients’ median age was 63 (range, 21 to 85) years.

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Most patients  had an Eastern Cooperative Oncology Group performance status of 0-1 (96.2%), stage III/IV disease (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 cycles (range, 1 to 8) of BR. Rituximab maintenance was given to 20.3% of patients for a median of 16 months, and 3.8% of patients received consolidation with involved-site radiation therapy.

The overall response rate (ORR) to frontline BR was 93.2%, with complete responses (CRs) in 81%, and partial responses (PRs) in 12.2%.

The median follow-up was 3.21 years. The estimated 5-year progression-free survival (PFS) rate was 80.5%, and the overall survival (OS) rate was 89.6%. The 5-year cumulative incidence of lymphoma-specific death was 3.8%, with 8 deaths due to lymphoma.

Researchers noted longer PFS with rituximab maintenance among patients who achieved a CR or PR following BR treatment (hazard ratio, 0.16; 95% CI, 0.04-0.71; P =.016). However, rituximab maintenance had no impact on the OS (P =.17).

When gastric EMZL was compared with other EMZL locations, no significant differences were observed in the PFS (P =.89) or OS (P =.49). In addition, MALT-IPI failed to predict PFS or OS.

On multivariate analysis, the presence of B symptoms and the absence of rituximab maintenance were significantly associated with shorter PFS.  

During BR therapy, 13% of patients experienced infectious complications, including herpes-zoster reactivation (4%), pneumonia (3%), and influenza (3%). In patients treated with rituximab maintenance, neutropenia occurred in 6.2%, herpes-zoster reactivation in 2%, and facial cellulitis in 2%.

Secondary malignancies after BR treatment were reported in 3.4% of patients. There was 1 case of acute myeloid leukemia and 1 case of squamous cell carcinoma of the skin. Biopsy-confirmed higher-grade transformation to diffuse large B-cell lymphoma occurred in 4.6% of patients.

“BR is a highly effective regimen in upfront treatment of EMZL, capable of inducing durable remissions, and possibly overcoming known adverse prognosis factors,” the researchers concluded. “This regimen is associated with occurrence of herpes-zoster and thus prophylactic treatment may be considered.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Alderuccio JP, Arcaini L, Watkins MP, et al. An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma. Blood Adv. Published February 23, 2022. doi:10.1182/bloodadvances.2021006844