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, N.J.--(BUSINESS WIRE)-- Bristol-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; P4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection.
Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before starting REVLIMID treatment and during therapy.
Early Mortality in Patients With MCL: In another MCL study, there was an increase in early deaths (within 20 weeks); 12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk factors for early deaths include high tumor burden, MIPI score at diagnosis, and high WBC at baseline (≥10 x 109/L).
Hypersensitivity: Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to REVLIMID has been reported. Permanently discontinue REVLIMID for angioedema and anaphylaxis.
ADVERSE REACTIONS
Multiple Myeloma
Myelodysplastic Syndromes
Mantle Cell Lymphoma
Follicular Lymphoma/Marginal Zone Lymphoma
DRUG INTERACTIONS
Periodically monitor digoxin plasma levels due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin-stimulating agents or estrogen-containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dexamethasone and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin.
USE IN SPECIFIC POPULATIONS
Please see full Prescribing Information, including Boxed WARNINGS, for REVLIMID.
For more information, please see the full SMPC related to the EC approval.
Please see the rituximab full Prescribing Information for Important Safety Information at www.rituxan.com.
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.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that the outcome of pricing and reimbursement negotiations in individual countries in Europe may delay or limit the commercial potential of Revlimid (lenalidomide), in combination with rituximab (anti-CD20 antibody), for the additional indication described in this release and whether Revlimid (lenalidomide), in combination with rituximab (anti-CD20 antibody), for such additional indication described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol-Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2018, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol-Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
_______________________________ 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.
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