Bristol-Myers Squibb Receives European Commission Approval for Revlimid® (lenalidomide) in Combination with Rituximab for the Treatment of Adult Patients with Previously Treated Follicular Lymphoma

Revlimid plus rituximab is the first chemotherapy-free combination regimen approved in Europe for patients with follicular lymphoma who have relapsed or did not respond to previous treatment

Approval was based on data from the phase 3 AUGMENT study, which showed statistically significant improvements in median progression-free survival in patients treated with the combination over rituximab-placebo monotherapy

PRINCETON, NJ, USA I December 20, 2019 IBristol-Myers Squibb Company (NYSE: BMY) today announced that the European Commission (EC) has approved a new indication for Revlimid (lenalidomide), in combination with rituximab (anti-CD20 antibody), for the treatment of adult patients with previously treated follicular lymphoma (FL) (Grade 1-3a). This combination of Revlimid and rituximab (R2) is the first chemotherapy-free combination regimen approved for patients with FL by the EC.

“This approval is a significant milestone for patients with follicular lymphoma whose disease is not responding to current therapy or has returned following prior treatment. In the phase 3 AUGMENT sudy, patients receiving R2 experienced extended periods of disease remission versus patients receiving rituximab plus placebo,” said Nadim Ahmed, President of Hematology at Bristol-Myers Squibb.

FL is a subtype of indolent, but incurable, non-Hodgkin lymphoma (NHL) which is associated with immune system dysfunction.1,2 There remains an unmet medical need for novel treatments for patients who have relapsed or become refractory to their previous treatment. It has been hypothesized that the combination therapy, R2, works with the patient’s immune system using the immunomodulatory properties of Revlimid along with the CD20 antibody-targeted mechanism of action of rituximab in order to help the patient’s own immune system fight the cancer.3

“Immune dysfunction is a defining aspect of indolent NHL, including follicular lymphoma,” said Prof. John Gribben, President of the European Hematology Association and Centre for Haemato-Oncology, Barts Cancer Institute, in England. “By utilizing the patient’s own immune system, R2 represents a new approach to treatment in follicular lymphoma, giving patients a chemotherapy-free option with demonstrated efficacy.”

The approval of R2 is based primarily on results from the randomized, multi-center, double-blind, phase 3 AUGMENT study, which evaluated the efficacy and safety of the R² combination versus rituximab plus placebo in patients with previously treated FL (n=295) or marginal zone lymphoma (MZL) (n=63).4

In AUGMENT, treatment with R2 demonstrated a statistically significant improvement in the primary endpoint of median progression-free survival (PFS) (EMA Censoring Rules), evaluated by an independent review committee, versus rituximab plus placebo. The median PFS was 39.4 months for FL patients treated with R2 and 13.8 months for those treated with rituximab-placebo (HR: 0.40; 95% CI, 0.29-0.55; P<0.0001). Median follow-up time was 29.2 months (range, 0.5-50.9) in the intent to treat population (n=295).4

In AUGMENT the adverse reactions of any grade observed more frequently in the FL R2 arm compared with the placebo/rituximab arm (with at least 2% higher frequency between arms) were neutropenia (58.2%), diarrhea (30.8%), leukopenia (28.8%), constipation (21.9%), cough (21.9%) and fatigue (21.9%).4

In addition to AUGMENT, findings from the MAGNIFY study were included as support for the safety and the efficacy of Revlimid plus rituximab in patients with relapsed or refractory FL, including rituximab refractory FL patients.5

About Follicular Lymphoma

Lymphoma is a blood cancer that develops in lymphocytes, a type of white blood cell in the immune system that helps protect the body from infection.6 There are two classes of lymphoma – Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) – each with specific subtypes that determine how the cancer behaves, spreads and should be treated.3,7,8 Other differentiating factors of lymphomas are what type of lymphocyte is affected (T cell or B cell) and how mature the cells are when they become cancerous.8

FL is the most common indolent (slow-growing) form of NHL, accounting for approximately 25% of all NHL patients.9,10 Most patients present with advanced disease when lymphoma-related symptoms appear (e.g., nodal disease, B symptoms, cytopenia) and receive systemic chemoimmunotherapy.9 While FL patients are generally responsive to initial treatment, the disease course is characterized by recurrent relapses over time with shorter remission periods.11

About AUGMENT

AUGMENT is a phase 3, randomized, double-blind clinical trial evaluating the efficacy and safety of Revlimid (lenalidomide) in combination with rituximab (R²) versus rituximab plus placebo in patients with previously treated follicular lymphoma (FL) or marginal zone lymphoma (MZL). AUGMENT included patients diagnosed with MZL or Grade 1, 2 or 3a FL, who were previously treated with at least 1 prior systemic therapy and two previous doses of rituximab.4 Patients were documented relapsed, refractory or progressive disease following systemic therapy, but were not rituximab-refractory.12

The primary endpoint was progression-free survival, defined as the time from date of randomization to the first observation of disease progression or death due to any cause.12 Secondary and exploratory endpoints included overall response rate, durable complete response rate, complete response rate, duration of response, duration of complete response, overall survival, event-free survival and time to next anti-lymphoma therapy.4,12

Bristol-Myers Squibb: Advancing Cancer Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase quality, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Revlimid

Revlimid is approved in Europe and the United States as monotherapy, indicated for the maintenance treatment of adult patients with newly diagnosed multiple myeloma (MM) who have undergone autologous stem cell transplantation. Revlimid as combination therapy is approved in Europe, in the United States, in Japan and in around 25 other countries for the treatment of adult patients with previously untreated MM who are not eligible for transplant. Revlimid is also approved in combination with dexamethasone for the treatment of patients with MM who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

Revlimid is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

In addition, Revlimid is approved in Europe for the treatment of patients with mantle cell lymphoma (MCL) and in the United States for the treatment of patients with MCL whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. In Switzerland, Revlimid is indicated for the treatment of patients with relapsed or refractory MCL after prior therapy that included bortezomib and chemotherapy/rituximab.

Revlimid is also approved in the United States in combination with a rituximab product. It is indicated for the treatment of adult patients with previously treated FL and adult patients with previously treated marginal zone lymphoma.

Revlimid is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

U.S. FDA-APPROVED INDICATIONS FOR REVLIMID®

REVLIMID® (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of adult patients with multiple myeloma (MM).

REVLIMID is indicated as maintenance therapy in adult patients with MM following autologous hematopoietic stem cell transplantation (auto-HSCT).

REVLIMID is indicated for the treatment of adult patients with transfusion-dependent anemia due to low-or intermediate-1–risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

REVLIMID is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.

REVLIMID in combination with a rituximab product is indicated for the treatment of adult patients with previously treated follicular lymphoma (FL).

REVLIMID in combination with a rituximab product is indicated for the treatment of adult patients with previously treated marginal zone lymphoma (MZL).

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

REVLIMID is only available through a restricted distribution program, REVLIMID REMS®.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

1 Scott DW, Gascoyne RD. The tumour microenvironment in B cell lymphomas. Nat Rev Cancer. 2014;14(8):517-534.
2 Kridel R, Sehn LH, Gascoyne RD. Pathogenesis of follicular lymphoma. J Clin Invest. 2012;122(10):3424-3431.
3 Chiu H, Trisal P, Bjorklund C, et al. Combination lenalidomide-rituximab immunotherapy activates anti-tumour immunity and induces tumour cell death by complementary mechanisms of action in follicular lymphoma. Br J Haematol. 2019;185(2):240-253.
4 Revlimid Summary of Product Characteristics. Available at https://www.ema.europa.eu/en/documents/product-information/revlimid-epar-product-information_en.pdf. Accessed December 2019
5 ClinicalTrials.gov Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma (MAGNIFY). Available at: https://clinicaltrials.gov/ct2/show/NCT01996865 Accessed August 2019.
6 American Cancer Society. Lymphoma. Available at: https://www.cancer.org/cancer/lymphoma.html. Accessed August 2019.
7 American Cancer Society. What is Hodgkin Lymphoma? Available at: https://www.cancer.org/cancer/hodgkin-lymphoma/about/what-is-hodgkin-disease.html. Accessed August 2019.
8 American Cancer Society. What is Non-Hodgkin Lymphoma? Available at: https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/what-is-non-hodgkin-lymphoma.html. Accessed August 2019.
9 European Society for Medical Oncology. Follicular Lymphoma: A Guide for Patients. 2014. Available at: https://www.esmo.org/content/download/52236/963497/file/EN-Follicular-Lymphoma-Guide-for-Patients.pdf. Accessed September 2019.
10 Lymphoma Action. Follicular lymphoma. Available at: https://lymphoma-action.org.uk/types-lymphoma-non-hodgkin-lymphoma/follicular-lymphoma. Accessed November 2019.
11 Montoto S, Lopez-Guillermo A, Ferrer A, et al. Survival after progression in patients with follicular lymphoma: analysis of prognostic factors. Ann Oncol. 2002;13(4):523-30.
12 ClinicalTrials.gov Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma) (AUGMENT). Available at: https://clinicaltrials.gov/ct2/show/NCT01938001 Accessed December 2019.

SOURCE: Bristol-Myers Squibb

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