Interim REFLECT Analysis Reconfirms Efficacy, Safety of Rituximab Biosimilar in DLBCL

Findings from the REFLECT interim analysis reconfirmed the expected efficacy and safety profile of the rituximab (Rituxan) biosimilar SDZ-RTX (Rixathon), in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL), according to Manfred Welslau, MD, who added that very little variance was found between the biosimilar and the reference product.

In the first real-world, prospective, post-approval study, investigators sought to evaluate a rituximab biosimilar as a curative therapy in untreated patients with CD20-positive DLBCL.

The analysis included a total of 120 patients who were treated with R-CHOP. The primary end point was complete response (CR) rate, which was assessed by the treating physician at the conclusion of therapy. The secondary end points of the trial included overall response rate (ORR), progression-free survival (PFS) at 24 months, safety, and quality of life.

Results presented during the 2020 ASCO Virtual Scientific Program showed that the ORR with the regimen was 88%; this was comprised of a 57% CR and a 31% PR. Efficacy data were missing for 9% of patients and not available for 3%. The PFS has not yet been reported. Additionally, 38% of patients completed the first 12-month observation period, 41% were still ongoing, and 21% discontinued treatment, mainly because of progressive disease (8%); adverse effects (AEs) resulted in the discontinuation of 8% of patients. The most common AEs reported with R-CHOP chemoimmunotherapy included anemia (24%), fatigue (21%), and polyneuropathy (15%).

“To date, up to 80% of patients in Europe are treated with the rituximab biosimilar as well as the trastuzumab (Herceptin) biosimilar,” Welslau explained. “We don’t see any difference between the rituximab biosimilar and the reference product.”

In an interview with OncLive, Welslau, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discussed the solidifying data from the interim analysis of the REFLECT trial with the rituximab biosimilar.

OncLive: Could you shed light on the advantage of biosimilars in general?

Welslau: Biosimilars have an advantage [over other products] because of the low market price; thus, more people have access to these therapies worldwide.

Could you speak to the approval process of biosimilars? How does it compare with that of a biologic?

Biosimilars have a different approval process because you only need 1 confirming clinical phase 3 study to obtain approval from the FDA and the European Medicines Agency. All of the other approved indications are within the label, after only 1 trial.

Moving specifically to the REFLECT trial, could you provide some background on the rituximab biosimilar and its current indications?

We decided to do this trial even though [the biosimilar] was already approved in Germany. The rituximab biosimilar was already approved because of the significant improvement in follicular lymphoma and [there was] exploration to all the other indications of [the reference] rituximab, even in rheumatic diseases. Since we need more data on [the biosimilar in] DLBCL, we wanted to show equal efficacy and toxicity [between] the Sandoz rituximab biosimilar [and the reference product].

What was the design of this trial and what methods were employed?

We didn't have any clinical data on biosimilars in combination with CHOP in patients with DLBCL. We decided to conduct a trial in over 30 centers in Germany using the rituximab biosimilar instead of reference rituximab. We examined the efficacy and toxicity of the therapy.

What did the results show?

These are only the interim results because we don't have the 24-month PFS data. I believe we will have them at the end of this year or the beginning of 2021; many of the patients were not in the longer follow-up until now. As you know, in DLBCL, the 24-month PFS is strongly correlated with OS.

We should see a good signal for the efficacy of the rituximab [biosimilar] in this patient population. Interim results [with the biosimilar] show the same efficacy, [with] an ORR of 88%, and the safety is the same as the original rituximab. As of now, we don't see any critical difference between the [products]. We now have [real-world] data on the rituximab biosimilar in this disease.

What are some of the common adverse effects (AEs)?

The main AEs [with the biosimilar] include anemia, neutropenia, and fatigue; these are the same toxicities that are observed with the original rituximab product. 

What is the significance of these results?

The take-home message is that you can use the rituximab biosimilar safely and effectively in the treatment of patients with DLBCL.

As more biosimilars for the same biologic enter the market, is it ultimately going to come down to payers in terms of what biosimilar is pursued in the clinic?

Yes, it's going to come down to the payers. In my clinic, we use a biosimilar from [one company] for a couple of months, and then we will the biosimilar from [another company] for a couple of months. This ultimately is decided by the payers.

Reference

Welslau M, Walter N, Otremba BJ, et al. REFLECT real-world evidence prospective study update: efficacy and safety results of Sandoz biosimilar rituximab for the treatment of diffuse large B-cell lymphoma. J Clin Oncol. 2020;38(suppl 15):8060. doi: 10.1200/JCO.2020.38.15_suppl.8060