Jan van de Winkel, PhD
Adding ofatumumab (Arzerra) to bendamustine (Treanda) failed to improve progression-free survival (PFS) in patients with indolent B-cell non-Hodgkin lymphoma (iNHL) who did not respond to rituximab (Rituxan) monotherapy or a rituximab-containing regimen, missing the primary endpoint of the phase III COMPLEMENT A+B trial.
Genmab, the manufacturer of the anti-CD20 antibody ofatumumab, reported the findings in a press release. The company plans to present the data at a future medical meeting.
"We are disappointed that the ofatumumab treatment regimen did not meet the primary endpoint in this trial. The completion of this phase III study, which began in 2010, would not have been possible without the generous participation of the patients and their families, and we are most grateful for this. The full data will be submitted for publication at a future medical conference and we hope that these will provide a better understanding of this result," Jan van de Winkel, PhD, chief executive officer, Genmab, said in a statement.
The open-label phase III COMPLEMENT A+B trial randomized 346 patients who had received prior rituximab to up to 8 cycles of bendamustine alone or combined with 12 doses of ofatumumab (1000 mg). There were no new safety signals observed with the treatments.
Despite the setback with this regimen, there have been several advances in recent years for patients with previously treated indolent lymphomas. In July 2014, the FDA approved idelalisib (Zydelig) for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma or relapsed small lymphocytic lymphoma (SLL) who have received at least 2 prior systemic therapies.
The approval was based on a single-arm phase II study of 125 patients with relapsed iNHL who were treated with idelalisib at 150 mg twice daily. The primary endpoint of the study was overall response rate (ORR), with secondary endpoints including duration of response and PFS.
The ORR in patients with follicular lymphoma (n = 72) was 54% (95% CI, 0.42-0.66). For patients with SLL, the ORR was 61% (95% CI, 0.41-0.79). For the entire population, the median time to response was 1.9 months, with a median duration of response of 12.5 months. The median PFS was 11 months and the median OS was 20.3 months.
In January 2017, the FDA granted an accelerated approval to ibrutinib (Imbruvica) as a treatment for patients with marginal zone lymphoma who require systemic following at least 1 prior anti-CD20–based therapy.
The approval was based on a single-arm, open-label phase II study in which the ORR with ibrutinib was 46%, with a complete response rate of 3.2%.1
The median PFS was 14.2 months with ibrutinib (95% CI, 8.3-NR) and the median overall survival was not yet reached at a median follow-up of 19.4 months.
The FDA is also currently reviewing a new drug application for the use of duvelisib for the treatment of patients with relapsed/refractory follicular lymphoma. The application is based on the phase II DYNAMO study, in which duvelisib demonstrated an overall response rate (ORR) of 46% (P
<.0001) for patients with indolent non-Hodgkin lymphoma (iNHL).2
The open-label phase II DYNAMO study, which began enrolling in May 2013, included patients with iNHL who were refractory to rituximab and either chemotherapy or radioimmunotherapy. Among the 129 enrolled patients, the disease types included follicular lymphoma (n = 83), SLL (n = 28), and marginal zone lymphoma (n = 18). Continuous duvelisib was administered at 25 mg twice daily.
The ORRs in the follicular lymphoma, SLL, and marginal zone lymphoma groups were 41%, 68%, and 33%, respectively. The median duration of response was 9.9 months. At a median follow-up of 11.5 months, the median OS in the entire iNHL population was 18.4 months and the median PFS was 8.4 months.
- Noy A, de Vos S. Thieblemont C, et al. Single-Agent Ibrutinib Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study. Presented at: ASH 2016 Annual Meeting. Abstract 1213.
- Verastem submits new drug application to US FDA for duvelisib for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. Verastem. Published February 7, 2018, Accessed April 9, 2018. http://bit.ly/2GT3m2u.