Rituximab Biosimilar CT-P10 Demonstrates Real-World Safety, Efficacy in DLBCL

The rituximab (Rituxan) biosimilar CT-P10 (Truxima) produced response and survival rates that were comparable to those previously reported with the reference product, along with acceptable tolerability, in patients with diffuse large B-cell lymphoma (DLBCL), according to real-world data from a European non-interventional post-authorization safety study.¹

Results, which were presented during the European Hematology Association 2021 Virtual Congress, showed that at 30 months post index, 67% (95% CI, 61.3%-72.1%) of patients who received the biosimilar as first-line treatment had not yet progressed. The overall survival rate was 74% (95% CI, 69.2%-79.1%).

Moreover, of the 382 patients who were observed, more than three-quarters of patents who received treatment with CT-P10 experienced either a complete or partial response to treatment at 30 months; these rates were 82% (n = 312) and 12% (n = 46), respectively. Four percent (n = 16) of patients achieved disease stability and 2% (n = 8) experienced progressive disease.

“These results support the use of CT-P10 in combination with chemotherapy as a therapeutic option for DLBCL,” lead study author Mark Bishton, MBChB, MRCP, FRCPath, PhD, consultant hematologist and honorary clinical associate professor at the University of Nottingham, School of Medicine, and colleagues, wrote in a poster on the data.

In February 2017, the rituximab biosimilar was granted approval from the European Medicines Agency for the treatment of several diseases, including non-Hodgkin lymphoma (NHL).² DLBCL represents 30% to 50% of all NHL cases. The decision was supported by evidence demonstrating clinical similarity between CT-P10 and the reference product in patients with rheumatoid arthritis and follicular lymphoma.^3,4

Notably, to date, patients with DLBCL have not been included in trials examining the biosimilar. Moreover, no prior studies have evaluated the safety and efficacy of CT-P10 in European patients in the real-world setting.

As such, investigators set out to examine the real-world clinical safety and efficacy of CT-P10 in patients with DLBCL residing in Europe as part of a non-interventional post-authorization safety study. This research was conducted in the following 5 European countries: France, Germany, Italy, Spain, and the United Kingdom.

To be eligible for inclusion, patients needed to be at least 18 years of age, have a confirmed diagnosis of DLBCL, have pre-index medical history data available, and at least 1 clinical response assessment in the 30 months post index, unless the patient was deceased. If patients had medical records that were unavailable for review, they were excluded from the analysis.

For the study, investigators reviewed data taken from the medical records of patients with DLBCL who received treatment with CT-P10 as part of routine clinical practice. Specifically, investigators looked at the date of diagnosis; collected baseline demographic and clinical characteristics and treatment history during the pre-index observation period; considered the date of treatment initiation; and then collected data regarding safety, clinical efficacy, and treatment patterns. Response findings were noted and documented by the local investigator.

The primary objective of the research was to characterize the clinical efficacy of the biosimilar in the treatment of patients with DLBCL with regard to OS, progression-free survival (PFS), and responses to treatment. Key secondary objectives comprised the safety profile of the agent; the demographic, clinical, and disease characteristics; and treatment patterns with the biosimilar.

Investigators defined OS as the time from the index date to death from any cause, and PFS was defined as the time from the index date to the first documented evidence of disease progression or death from any cause.

The trial enrolled a total of 389 patients, and participants had a median age of 69.7 years (range, 60.3-76.1) and 58% were male. The age at diagnosis of DLBCL was 69.5 years (range, 60.0-75.7), and the median disease duration from diagnosis to index date was 23.0 days (range, 12.0-46.0). The majority of patients had an ECOG performance status of 0 or 1 (79%), Ann Arbor stage IV disease at index (51%), an International Prognostic Index score of 3 (26%) at index.

Of the 389 patients, 84% received the biosimilar as first-line treatment, 11% received it in the second-line setting, 4% in the third line, 1% in the fourth line, and 1% in the fifth-, six-, and seventh-line setting (n = 1 each).

Sixty-eight percent of patients received the biosimilar with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulphate, and prednisolone (R-CHOP); 7% received R-mini-CHOP; 6% received R-CHOP with methotrexate; 2% received rituximab with gemcitabine, cyclophosphamide, vincristine, and prednisolone; 2% were given rituximab monotherapy; 1% received dose-adjusted etoposide, prednisone, and vincristine; and 13% receive other chemotherapy.

Regarding safety, 90% of participants (n = 351/389) experienced an adverse effect (AE) with the biosimilar during the observation period; a total of 2504 AEs were observed, overall. Of these effects, 51% were grade 3 or higher in severity. Twenty-four patients (6%) reported AEs that resulted in treatment discontinuation.

Toxicities that were experienced by more than 10 patients with DLBCL treated with CT-P10 included general disorders and administration site conditions (n = 220), gastrointestinal disorders (n = 209), nervous system disorders (n = 161), blood and lymphatic system disorders (n = 136), and infections and infestations (n = 134), among others.

Moreover, 9% (n = 180) of the 2100 AEs, not including serious AEs, were recorded as definitely, probably, or possibly related to the biosimilar. Infusion-related reactions were experienced on days 1 or 2 following infusion for 8% (n = 31) of 389 patients.

“This is the first multi-country retrospective post-approval study to investigate the effectiveness and safety of CT-P10 treatment in patients with DLBCL in the real-world setting across Europe,” Bishton stated in a press release.⁵ “The response rates, survival rates, and overall safety profile for CT-P10 appears consistent with those reported for reference rituximab, which could support the use of CT-P10 in combination with chemotherapy as a therapeutic option for DLBCL.”

In November 2018, CT-P10 was approved by the FDA as the first biosimilar for use in adult patients with CD20-positive B-cell NHL as a monotherapy or in combination with chemotherapy based on data that included extensive structural and functional characterization, animal study findings, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that showed similarity between the biosimilar and the reference product.⁶

References

1. Bishton M, Laribi K, Salles G, et al. Real-world clinical effectiveness and safety of CT-P10 in patients with diffuse large B-cell lymphoma: results from a European non-interventional post authorization safety study. Presented at: European Hematology Association 2021 Virtual Congress; June 9-19, 2021; virtual. Abstract EP529. https://bit.ly/3zqSBje
2. Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116(19):3724-3734. doi:10.1182/blood-2010-05-282632
3. Yoo DH, Suh C-H, Shim SC, et al. Efficacy, safety, and pharmacokinetics of up to two courses of the rituximab biosimilar CT-P10 versus innovator rituximab in patients with rheumatoid arthritis: results up to week 72 of a phase I randomized controlled trial. BioDrugs. 2017;31(4):357-367. doi:10.1007/s40259-017-0232-7
4. Kim WS, Buske C, Ogura M, et al. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol. 2017;4(8):e362-e373. doi:10.1016/S2352-3026(17)30120-5
5. Celltrion Healthcare presents the first real-world data for Truxima (biosimilar rituximab) in patients with diffuse large B-cell lymphoma at the EHA 2021 Virtual Congress. News release. Celltrion Healthcare. June 12, 2021. Accessed June 12, 2021. https://bit.ly/3pQVdCu
6. FDA approves first biosimilar for treatment of adult patients with non-Hodgkin’s lymphoma. News release. FDA. November 28, 2018. Accessed June 12, 2021. https://bit.ly/2KD2hOu