Long-term Safety of Rituximab Biosimilar in Untreated Advanced FL

Christian Buske, MD, Medical Director, University Hospital Ulm, Germany, overviews a randomized phase 3 study on the long-term safety and efficacy of CT-P10, a rituximab biosimilar, in patients with untreated advanced follicular lymphoma (FL).

Transcript:

My name is Christian Buske. I'm a hematologist/oncologist at the University Hospital of Ulm; Medical Director at this University Hospital; and my focus is on clinical research in the field of B-cell lymphomas.

Oncology Learning Network: What existing data led you and your co-investigators to conduct this research?

Dr Buske: What we know is that in advanced stage FL, rituximab in combination with chemotherapy followed by rituximab maintenance is still the standard today. You find this treatment recommendation in all national and international treatment guidelines.

Based on this, it was our interest to see how a rituximab biosimilar actually behaves in the setting. In that sense, we also wanted to test whether with long-term follow-up, the rituximab biosimilar in this environment is as efficient as the originator and if the toxicity profile is comparable to the original product.

With this in mind, we initiated a randomized phase 3 study—actually placebo or double-blind phase 3 study. It was a 1:1 randomization, so 50% of the patients received rituximab, the original product, plus CVP [cyclophosphamide, vincristine sulfate, and prednisone] followed by rituximab maintenance. The experimental arm used the rituximab biosimilar, CT-P10, combined with CVP, and then CT-P10 maintenance.

This was the study design, very straightforward, randomized, double-blind, to be sure that we are not compromising anything when we offer our patients rituximab biosimilar compared to the original product.

OLN: Could you briefly describe the study and its design?

Dr Buske: It's a randomized, phase 3 study, double-blind, in patients with advanced-stage, treatment-naïve FL.

One treatment arm was an induction treatment with rituximab CVP followed by rituximab maintenance—so you are using the originator.

The experimental arm was exactly the same but substituting the original product with CT-P10, which was the first approved rituximab biosimilar in the United States and also in Europe.

The study randomized 140 patients, so 70 patients per arm. It was quite a large study and tested different parameters. There were 2 primary or coprimary end points: response rate and pharmacokinetics. This was already published, earlier reports being the same.

This recent publication, with a longer follow up of nearly 40 months, looked not only at response rates and toxicities again, but also looked at event-driven parameters, such as progression-free survival (PFS), time to treatment failure, duration of response (DOR).

OLN: What were the study findings? Were any of the outcomes particularly surprising?

Dr Buske: As mentioned before, in the previous report, the focus was on these coprimary end points. In this analysis, which we just recently published with this long follow-up, we were highly interested to see about PFS and DOR: are there any differences?

It was not surprising, it was what we expected, but I think it's very important to confirm these expectations in a clean, randomized, perspective, phase 3 trial, even double-blinded.

What we found was that the overall response rate (ORR) and importantly, also these event-driven parameters, PFS, time to treatment failure, DOR, were comparable, confirming that indeed the CT-P10 is equipotent to the original rituximab product.

Why is this so important? Because for us, when we treat FL which is an indolent lymphoma subtype, the parameter (ie, PFS) is very important.

So as said, this was not among the coprimary end points of the study. The more important it was that we confirmed that beyond these coprimary end points of pharmacokinetics and response rate also that these parameters—which are very important for the acceptance of biosimilars in the community—are really the same or comparable.

This is what was nicely shown in this publication. We really do not see any difference, underlining that we can really feel safe when we prescribed rituximab biosimilars such as CT-P10 to our patients.

OLN: What are the possible real-world applications of these findings in clinical practice?

Dr Buske: I think it's now very clear that with this long follow-up in advanced-stage FL using a standard regimen, such as rituximab, CVP as induction, followed by rituximab maintenance, which really corresponds to our standard treatment recommendations.

Seeing now that there is no difference, it has the consequence for the real-world setting that we can just encourage our colleagues to prescribe CT-P10 as a rituximab biosimilar.

Why this? Because it's saving costs, very simple. And of course, I'm now sitting in a rich country being located in Germany. But we know that the access to rituximab is a problem in many areas in the world based on, or because of costs, very simple. I think that these biosimilars are saving costs, but for some countries it's the only possibility to get access to this anti-CD20 antibody.

With these data in mind, one can feel very comfortable to prescribe rituximab biosimilars in particular, in countries here in the world which otherwise would not have even access to this very important compound or drug, which we really need for controlling indolent B-cell lymphomas, such as FL.

Very clearly this has direct consequences for the real-world setting. Absolutely. Even in my country, the proportion of biosimilars use is very high. In the United Kingdom, it's I think 70%, 80%, 90% biosimilars are prescribed. It has really changed the real-world setting.

OLN: Do you and your co-investigators intend to expand upon this research? If so, what will be your next steps?

Dr Buske: With this data set we can be absolutely sure that for FL, there is no difference. I think it will be important nevertheless, to follow up the use of biosimilars in our communities. It's important to have registries in B-cell lymphomas, which actually document the use of biosimilars, not only in FL, but also in other lymphoma subtypes.

We know that rituximab is still the cornerstone of treatment for diffuse large B-cell lymphoma, for mantel cell lymphoma, for marginal zone lymphoma, and for Waldenström macroglobulinemia. For all these B-cell lymphomas, rituximab is very important.

To document the use of biosimilars, the efficacy and toxicity of these biosimilars, in registries for these different lymphoma subtypes, I think is very important.

Another kind of research we are really willing to use rituximab biosimilars also in combination with novel agents. As a partner for emerging new treatment options, such as BCL-2 inhibitors, venetoclax for instance, for PI3K inhibitors, such as copanlisib, and we are conducting academic trials combining CT-P10 or other rituximab biosimilars with novel agents. In that sense, we are continuing our research on biosimilars.

Source:

Buske C, Jurczak W, Sancho JM, et al. Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study. Blood Adv. 2021;5(17):3354-3361.