Non-Hodgkin Lymphoma Shows Significantly Better Outcomes with Obinutuzumab, Bendamustine Combo

Non-Hodgkin Lymphoma Shows Significantly Better Outcomes with Obinutuzumab, Bendamustine Combo

Patients with non-Hodgkin lymphoma (NHL) who are resistant to rituximab therapies show greater benefits when treated with a obinutuzumab and bendamustine combination, compared to the standard bendamustine alone, according to data from the GADOLIN Phase 3 trial.

The study, “Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial,” was published in Lancet Oncology.

In recent decades, the outcomes of NHL patients improved significantly mostly due to the integration of the anti-CD20 monoclonal antibody  rituximab into treatment regimens, either as a single drug or in combination with chemotherapy. Rituximab improved patients response rates, progression-free survival (PFS), and overall survival (OS) in patients with advanced stage disease.

But some patients fail to respond with rituximab. Such patients have poor prognosis and their treatment options show a short-term benefit. Approved therapeutic options for rituximab-refractory patients include ⁹⁰Y-ibritumumab tiuxetan, with an overall response of 74 percent and median PFS of 6.8 months, and bendamustine, which has an overall response of 75 percent and median PFS of 9.3 months.

Recently, attempts to develop new CD20-targeting therapies that could overcome the resistance to rituximab have occurred. Particularly, researchers have been trying to develop anti-CD20 antibodies that target distinct parts of the CD20 molecule or with enhanced ability to induce cancer cell death.

Obinutuzumab (marketed as Gazyva/Gazyvaro), is a glyco-engineered anti-CD20 monoclonal antibody.

In early clinical trials, obinutuzumab showed encouraging activity in patients with relapsed indolent (slow-growing) non-Hodgkin lymphoma and responses were noted in rituximab-refractory patients, suggesting that combining obinutuzumab with the standard of care bendamustine could potentially benefits patients that failed to respond or progress on rituximab.

The hypothesis was evalutated in the GADOLIN study, an open-label, randomized, Phase 3, international trial. The study evaluated the safety and efficacy of the combination versus bendamustine alone with 396 rituximab-refractory indolent NHL patients from 14 different countries worldwide. Non-progressing patients in the obinutuzumab plus bendamustine group also received obinutuzumab maintenance for up to 2 years.

After a median follow-up of 21.9 months, the 196-patient obinutuzumab plus bendamustine group had not reached its median PFS, while the 202-subject bendamustine group, with a median follow-up of 20.3 months, had a median PFS of 14.9 months, which was significantly lower than that observed with the combined therapy. No differences were found in overall survival.

Major adverse side effects such as decreased platelet and neutrophil levels, anemia, and infusion-related reaction, were equal between the two groups and manageable.

Despite the benefits in PFS, there were no measurable differences in the overall response or complete response, suggesting that the combination therapy changes the quality of the remission. In fact, patients in the obinutuzumab plus bendamustine group were more likely to be minimal residual disease negative (with lower amount of disease) after the combo than the patients who received bendamustine alone, which was associated with a longer PFS.

Minimal residual disease positive patients did not benefit from the obinutuzumab maintenance therapy, revealing that minimal residual disease status may be good for helping identify patients that will benefit from the therapy.

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