Study Supports Bendamustine-Rituximab as Standard-of-Care in Patients With Indolent Non-Hodgkin Lymphoma

The efficacy and safety of bendamustine-rituximab (BR) for treatment of patients with indolent non-Hodgkin lymphoma (NHL) was comparable in a real-life cohort to data from prior studies, supporting its use as a standard-of-care treatment, according to the results of a trial published in Cureus.¹

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NHLs are a heterogeneous group of malignancies, including follicular lymphoma (FL), small lymphocytic lymphoma (SLL), and certain cases of mantle cell lymphoma (MCL), among others. Front-line treatment of NHLs includes a combination of immunotherapy and chemotherapy.¹

Bendamustine, a cytotoxic alkylating agent, has shown proven efficacy in the treatment of NHLs in clinical trials. Other chemotherapy regimens were commonly used as frontline treatments until the publishing of the BRIGHT trial. The study authors found that the complete response rate for first-line BR was statistically noninferior to 2 other common therapy regimens.²

Another efficacy and safety trial, the phase 3 SHINE study, indicated that the combination of once daily ibrutinib plus BR lowered the risk of disease progression or death by 25% compared to placebo in patients with newly diagnosed MCL.³

After the publication of those trials and others, the BR combination became an increasingly used first-line option for the treatment of indolent NHL. However, existing data on the safety and efficacy of rituximab maintenance after bendamustine remains limited.¹

The investigators adopted the frontline BR regimen for patients with indolent NHL in a hospital in Montreal and aimed to evaluate the real-world therapy of the treatment.¹

A total of 42 adults were treated with BR from January 2015 to August 2018. Rituximab was received at the dose of 375 mg/m² on day 1 of each cycle, with patients receiving an intravenous infusion of bendamustine at the standard dose of 90 mg/m² or at a reduced dose of 60 mg/m², continued for 6 cycles over 4 weeks.¹

For the planned 6 cycles of BR, 33 patients (79%) completed all 6. Only 1 patient received a reduced dose of bendamustine, and they still completed 6 cycles. The main reason for discontinuation among those who did so (total n = 9) was due to toxicities (n = 7, 78%).¹

The overall response rate (ORR) in their cohort was 84%, with 62% of patients achieving a complete response and 22% receiving a partial response. An overall survival (OS) estimation was impossible due to the small number of samples in the study. Progression-free survival was 74.8% at 30 months follow-up, while OS was 90%.¹

Neutropenia was the most common grade 3-4 hematological adverse event (AE) related to BR therapy, which occurred in 21% of patients. There were infection-related AEs observed in 17 patients (40%), though most were of mild-to-moderate severity; the most common were fatigue and mild nausea.¹

In the BRIGHT trial, ORR was 96.7%. Though the ORR found in the current study is slightly lower, the PFS appears to be comparable to what has been reported previously in the literature, according to the investigators. A key point is the shot follow-up period – only 29.2 months – indicating that only a few patients demonstrated disease progression, as seen in the BRIGHT trial.^1,2

The investigators felt that the treatment was well-tolerated in the younger population of their study but noted that tolerance could be difficult for patients over 70 tears old. In the case of treatment difficulties with older patients, the investigators wrote that alternative chemotherapy backbones with fewer toxicities is acceptable.¹

Despite BR’s favorability as a first-line treatment, the investigators expressed caution that it may not be the best treatment option for all patients. Depending on the patient’s fitness or presentation with comorbidities, alternative treatment options that are more tolerable and less toxic should be considered.¹

“Additional follow-up is warranted to determine long-term PFS and OS in our cohort,” the study authors concluded. “Future studies should assess whether the use of G-CSF as primary prophylaxis effectively mitigates the hematological and infectious adverse events related to BR therapy.”¹

REFERENCES

1. Chan T, Champagne JN, Boudreault JS. Efficacy and safety of bendamustine-rituximab as frontline therapy for indolent non-Hodgkin lymphoma: a real-world, single-center, retrospective study. Cureus. 2024;16(8):e66124. doi:10.7759/cureus.66124

2. Flinn I, van der Jagt R, Kahl B, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014:123(19):2944-2952. doi:10.1182/blood-2013-11-531327

3. Gallagher A. Chemoimmunotherapy with ibrutinib shows improved survival over standard of care in mantle cell lymphoma. Pharmacy Times. Published June 4, 2022. Accessed August 12, 2024. https://www.pharmacytimes.com/view/chemoimmunotherapy-with-ibrutinib-shows-improved-survival-over-standard-of-care-in-mantle-cell-lymphoma