New Phase II data indicate regimen of Truxima® (biosimilar rituximab), lenalidomide and acalabrutinib (R2A) may be well tolerated and effective in relapsed/refractory aggressive B-cell lymphoma

• Data from a Phase II trial show a regimen of Truxima^® (biosimilar rituximab), lenalidomide and acalabrutinib (R2A) was well tolerated in people with relapsed/refractory aggressive B-cell lymphoma^[i]
• Biosimilars have the potential to enable access to novel drugs and regimens by reducing the overall cost burden of treatment
• Celltrion Healthcare is committed to driving innovative research within haematology to support patients

MONDAY 15^TH JUNE – 09:00 KST, INCHEON, SOUTH KOREA – Data presented as part of the Virtual Edition of the 25^th EHA Annual Congress (EHA25 Virtual Congress) show that a regimen of Truxima^® (biosimilar rituximab), lenalidomide and acalabrutinib (R2A) may be well tolerated and effective in relapsed/refractory aggressive B-cell lymphoma.¹ Lenalidomide and Bruton’s tyrosine kinase (BTK) inhibitors have shown potential in the treatment of aggressive B-cell lymphoma, and recent studies suggest both agents may be particularly effective in a subset of large B-cell lymphomas. The objective of this Phase II clinical trial was to evaluate the toxicity and efficacy of the R2A regimen in relapsed/refractory aggressive B-cell lymphoma.¹

Between the first enrolment in July 2019 and the data cut-off in February 2020, a total of 22 patients were treated with a median follow up of 3.2 months. The majority of patients (73%) had non-germinal centre B-cell like diffuse large B-cell lymphoma (non-GCB DLBCL). In each cycle of treatment, patients were treated with rituximab 375mg/m² day 1 intravenous injection, lenalidomide 20mg day 1 to day 21 once daily, and acalabrutinib 100mg day 1 to day 28 twice daily. Each cycle of treatment was delivered over 4 weeks (28 days), and each patient received 6 cycles. Acalabrutinib maintenance therapy was then given in responders for up to one year.¹

The primary endpoint for this single arm, multicenter, investigator-initiated study was the overall response rate (ORR) and secondary endpoints included complete remission (CR) rate, progression free survival (PFS), overall survival (OS) and safety profile. In the 13 patients who underwent disease assessment following the R2A regimen, objective response was observed in 69% of patients and CR was observed in 31% of patients. The 6-month PFS rate was 83% and only one patient experienced disease progression after the initial objective response.¹

Throughout the study, out of 22 patients, dose reduction was performed in 3 and 1 patients for lenalidomide and acalabrutinib respectively due to haematologic toxicities. 3 patients experienced higher than grade 2 toxicity and the most common adverse event regardless of grade was skin toxicity, observed in 4 patients. The data indicate that the R2A regimen was therefore well tolerated in Korean relapse/refractory B-cell lymphoma patients, with initial analysis in non-GCB DLBCL patients showing a promising response.¹

Combination regimens can improve patient outcomes, however, combining high-cost treatments can make the cost unsustainable. Payers are therefore increasingly looking for new pricing models and ways to manage the budget impact of combination treatments.^[ii] The introduction of biosimilar rituximab to the R2A regimen may have the potential to reduce the overall cost of treatment.

Youngil Koh, Associate Professor at Seoul National University Hospital and principal investigator of the trial, said, “Despite the introduction of new drugs for the treatment of lymphoma, there has been rising concern over the cost of treatment. Biosimilars have the potential to explore better treatment regimens and increase access to novel drugs and new regimens. By incorporating biosimilar rituximab into combination therapies alongside new drugs, the overall cost burden can be reduced, enhancing patient access.”

Mr. Hyoung-Ki Kim, Vice Chairman at Celltrion Healthcare said, “There is a rising interest towards lenalidomide and acalabrutinib in the haematology community and Celltrion Healthcare is committed to continuing its innovative research into new regimens such as R2A combination therapy to support patient care.”

Recently, the WHO recognised the importance of access to rituximab and awarded prequalification to Truxima^®, making this the first rituximab similar biotherapeutic product to be prequalified by the organisation.^[iii] Mr Kim said, “The prequalification of this treatment marks another step forward in making this medicine available in many countries around the world as an affordable therapeutic option.”

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Notes to Editors:

About diffuse large B-cell lymphoma (DLBCL) ^{[iv],[v],[vi],[vii]}

There are more than 60 different subtypes of Non-Hodgkin’s lymphoma (NHL), however diffuse large B-cell lymphomas (DLBCLs) are the most common subtype accounting for 30-40% of adult NHLs. Global epidemiological data is limited, however, it is thought that the incidence is 7 cases per 100,000 people.

DLBCL is an aggressive condition and it is common to find patients with advanced disease at the point of diagnosis. The most commonly exhibited symptom is one or more painless swellings, and other general symptoms include heavy sweating at night, high temperatures that arise with no obvious cause and weight loss. Of DLBCL patients, 30-40% are thought to relapse and 10% of patients have refractory disease. Patients with relapsed refractory DLBCL if left untreated have a life expectancy of 3 to 4 months.

About Truxima^® (biosimilar rituximab)^3,[viii]

Truxima^® is a mAb that targets CD20, a transmembrane protein found on the surface of most B-cells. By binding specifically to CD20, Truxima^® depletes B-cells by three main mechanisms: Induction of apoptosis, stimulation of CDC (complement-dependent cytotoxicity) and stimulation of ADCC (antibody-dependent cell-mediated cytotoxicity). Truxima^® approved in the EU for the treatment of patients with Non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. Truxima^® is the first rituximab similar biotherapeutic product to be prequalified by the World Health Organization (May 2020).

About Celltrion Healthcare

Celltrion Healthcare is committed to delivering innovative and affordable medications to promote patients’ access to advanced therapies. Its products are manufactured at state-of-the-art mammalian cell culture facilities, designed and built to comply with the US FDA cGMP and the EU GMP guidelines. Celltrion Healthcare endeavours to offer high-quality cost-effective solutions through an extensive global network that spans more than 110 different countries. For more information please visit: https://www.celltrionhealthcare.com/en-us

[i] Koh, Y., Park, C., Byun, J., et al. Rituximab, lenalidomide and acalabrutinib (R2A) for relapsed/refractory aggressive B-cell lymphoma: Interim analysis reporting good tolerability and potential durable response. Poster presented at: EHA25 Virtual Congress; June 12, 2020

[ii]Sherwin, G et al. Payer Management Of High-Cost Brand-On-Brand Combination Therapies In Oncology. Value in Health. 2017;20(9):A461. Doi:https://doi.org/10.1016/j.jval.2017.08.357

[iii] First rituximab similar biotherapeutic products prequalified. World Health Organization. Available at: https://extranet.who.int/prequal/news/first-rituximab-biotherapeutic-products-prequalified Last accessed June 2020

[iv] NHL subtypes. Leukemia & Lymphoma Society. Available at: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/diagnosis/nhl-subtypes Last accessed June 2020

[v] Raut LS, Chakrabarti PP. Management of relapsed-refractory diffuse large B cell lymphoma. South Asian J Cancer. 2014;3(1):66‐70. doi:10.4103/2278-330X.126531

[vi] Vivek Kumar, Sarvadaman Makardhwaj Shrivastava, Trishala Meghal and Binod Abhinav Chandra (June 27th 2018). Recent Advances in Diffuse Large B Cell Lymphoma, Hematology - Latest Research and Clinical Advances, Margarita Guenova and Gueorgui Balatzenko, IntechOpen, DOI: 10.5772/intechopen.74263. Available from: https://www.intechopen.com/books/hematology-latest-research-and-clinical-advances/recent-advances-in-diffuse-large-b-cell-lymphoma Last accessed June 2020

[vii] Diffuse large B cell lymphoma. Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/types/diffuse-large-B-cell-lymphoma Last accessed June 2020

[viii] European Medicines Agency Summary of Product Characteristics (SmPC). Truxima. Available at https://www.ema.europa.eu/en/documents/product-information/truxima-epar-product-information_en.pdf Last accessed June 2020