Manfred Welslau, MD, a specialist in Internal Medicine, as well as Hematology and Oncology with Onkologie Aschaffenburg, discusses the rationale of the prospective REFLECT trial with the rituximab (Rituxan) biosimilar SDZ-RTX (Rixathon) in patients with diffuse large B-cell lymphoma (DLBCL).

In the REFLECT trial, SDZ-RTX was administered in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (Deltasone) to patients with DLBCL. The REFLECT trial was conducted even though the rituximab biosimilar was already approved in Germany, says Welslau. The agent was approved because of the significant benefit it provided to patients with follicular lymphoma. Additionally, there was exploration of all other indications of rituximab, even in rheumatic diseases.

More data are needed to understand how the biosimilar performs in DLBCL. As such, the REFLECT trial was launched to confirm equal efficacy and toxicity between reference rituximab and the Sandoz rituximab biosimilar, concludes Welslau.

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Manfred Welslau, MD, discusses the rationale of the prospective REFLECT trial with the rituximab biosimilar SDZ-RTX in patients with diffuse large B-cell lymphoma.

Dr. Welslau on the Rationale for the REFLECT Trial With Rituximab Biosimilar

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses​ the interim results of the REFLECT trial in diffuse large B-cell lymphoma (DLBCL).

The REFLECT study is the first prospective post-approval trial evaluating the safety and efficacy of SDZ-RTX (Rixathon), a rituximab (Rituxan) biosimilar, in patients with untreated CD20-positive DLBCL.

As the field awaits the 24-month progression-free survival data, interim results from the study, presented during the 

, re-confirm the expected safety and efficacy profile of this biosimilar in patients with DLBCL. 

Moreover, the overall response rate with SDZ-RTX was 88% with a complete response rate of 57% and partial response rate of 31%.

These real-world data do not suggest there are any significant differences between the biosimilar and the biologic, concludes Welslau.

Manfred Welslau, MD, discusses​ the interim results of the REFLECT trial in diffuse large B-cell lymphoma.  



Dr. Welslau on the Interim Results of the REFLECT Trial in DLBCL 

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses​ the potential benefits of ​using biosimilars in diffuse large B-cell lymphoma (DLBCL).

Due to low​er market price​s, biosimilars offer a more accessible ​options to patients in ​developed and underdeveloped countries, Welslau explains.

Notably, biosimilars have a different approval process compared with biologics​, says Welslau. If the biosimilar agentdemonstrates clinical similarity to the reference biologic and does not demonstrate clinically meaningful differences regarding safety and efficacy, only 1 confirmatory phase 3 study is required to receive FDA and European Medicines Agency approval, Welslau concludes.

Manfred Welslau, MD, discusses​ the potential benefits of ​using biosimilars in diffuse large B-cell lymphoma.

Dr. Welslau on the Benefits of Biosimilars in DLBCL   

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses the rationale for investigating the Sandoz rituximab (Rituxan) biosimilar, Rixathon, in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in diffuse large B-cell lymphoma (DLBCL).

As part of the 2020 ASCO Virtual Scientific Program, findings from a real-world, prospective, post-approval study of the rituximab biosimilar plus CHOP provided additional evidence regarding the expected efficacy and safety profile of the combination in patients with previously untreated DLBCL.

The trial evaluated the agent in over 30 centers in Germany, says Welslau. Moreover, Rixathon continues to demonstrate clinical similarity to its biologic counterpart. 

Manfred Welslau, MD, discusses the rationale for investigating the Sandoz rituximab biosimilar, Rixathon, in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone in diffuse large B-cell lymphoma.



Dr. Welslau on the Rationale for Rituximab Biosimilar Combination in DLBCL

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses the first interim safety analysis in treatment-naïve, CD20-positive diffuse large B-cell lymphoma (DLBCL) following the approval of Rixathon, a Sandoz biosimilar for rituximab (Rituxan).

The multicenter, open-label REFLECT trial recruited 80 patients 18 years or older who were eligible to receive product-label rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP).

The primary endpoint of REFLECT is complete remission. Secondary endpoints are progression-free survival at 12 months, as well as overall survival and adverse events (AEs).

Interim baseline data and safety results were as expected. Polyneuropathy (n = 10, 12.5%), anemia (n = 8, 10%) and fatigue (n = 8, 10%) were the most commonly reported AEs. Overall, AEs were reported in 66% of patients with 24% reporting serious AEs.

The study is ongoing, but Weslau is optimistic about the totality of evidence for biosimilarity and for future biosimilar application in this space.


Manfred Welslau, MD, discusses the first interim safety analysis in treatment-naïve, CD20-positive diffuse large B-cell lymphoma following the approval of Rixathon, a Sandoz biosimilar for rituximab.
 

Dr. Welslau on REFLECT Interim Safety Analysis in DLBCL

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses the rationale for the prospective, multicenter, open-label REFLECT trial in diffuse large B-cell lymphoma (DLBCL).

In 2017, the European Medicines Agency approved Rixathon (SDZ-RTX), a Sandoz biosimilar for rituximab (Rituxan) for the same indications as the reference product. In August 29, 2017, data from the ASSIST-FL trial, published in 

, demonstrated the similarity of the biosimilar to the reference biologic in patients with follicular lymphoma.

The REFLECT trial was launched after the approval of the biosimilar to evaluate its efficacy as a curative therapy in combination with CHOP (cyclophosphamide, doxorubicin, hydrochloride, vincristine sulfate, and prednisone) in patients with previously untreated CD20-positive DLBCL, says Welslau. The trial sought to the confirm the similarity of the Sandoz biosimilar to reference biologic in this patient population.

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses the rationale for the REFLECT trial in diffuse large B-cell lymphoma.

Dr. Welslau on the Rationale for the REFLECT Trial in DLBCL

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses financial savings of using a rituximab (Rituxan) biosimilar for patients with previously untreated CD20-positive diffuse large B-cell lymphoma (DLBCL).

Germany has about 25% cost savings by using the biosimilar rituximab versus the original drug, says Welslau, in part due to the large population in the country. Welslau believes Europe can save about a half-billion euros by using biosimilars.

The low cost of biosimilar rituximab allows increased access of therapy, which is especially significant for developing countries where many people are waiting for treatment, according to Welslau.

Manfred Welslau, MD, discusses financial savings of using a rituximab biosimilar for patients with previously untreated CD20-positive diffuse large B-cell lymphoma.

Dr. Welslau on Financial Savings of Biosimilar Rituximab in DLBCL

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses the growing acceptance of a rituximab (Rituxan) biosimilar in the treatment of patients with diffuse large B-cell lymphoma (DLBCL), following favorable results from a safety analysis of the REFLECT study.

In Europe, the biosimilar sandoz rituximab (SDZ-RTX) has received approval for the same indications as reference rituximab (Rituxan) based on the totality of evidence for biosimilarity. REFLECT, the first post-approval rituximab biosimilar study to be done in DLBCL, aims to evaluate the use of the rituximab biosimilar in patients with treatment-naïve CD20-positive disease as curative therapy.

Data from an interim analysis of the study presented at the 2019 ASCO Annual Meeting showed that of the 80 patients evaluated in the trial, most experienced little to no restriction in daily activities. B-symptoms were reported in 15 patients, extranodal infiltration was noted in 40 patients, and bulky disease was observed in 9 patients. However, these safety data were expected based on what has been seen with rituximab-based treatment.

Biosimilar use in non-curative treatment is largely accepted, but acceptance regarding the use of these products in the curative setting is pending. Welslau hopes that data from the REFLECT trial will encourage more acceptance of these products in the treatment of this population as the study continues.

Proving the process behind the development of SDZ-RTX is what will be necessary in order to gain approval for the agent worldwide. Welslau adds that the charge variants of rituximab are already changing and sandoz rituximab is just another charge.

Manfred Welslau, MD, Internal Medicine, Hematology and Oncology, Onkologie Aschaffenburg, discusses the growing acceptance of a rituximab (Rituxan) biosimilar in the treatment of patients with diffuse large B-cell lymphoma, following favorable results from a safety analysis of the REFLECT study.

Manfred Welslau, MD

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