Phase 3 Data Published in The Lancet Show Bendamustine (Levact®) Plus Rituximab Doubles Progression-Free Survival in Patients With Indolent Non-Hodgkin Lymphoma and Mantle Cell Lymphoma Compared With CHOP-R PR Newswire CAMBRIDGE, England, February 20, 2013 CAMBRIDGE, England, February 20, 2013 /PRNewswire/ -- NOT INTENDED FOR MEDIA IN THE NETHERLANDS -Treatment with bendamustine plus rituximab (B-R) doubles progression free survival (PFS) compared with current standard of care CHOP-R (69.5 versus 31.2 months; p<0.0001) - B-R better tolerated than CHOP-R in study designed to explore simplified regimen as new first-line treatment - Data adds to growing body of clinical evidence that demonstrates anti-cancer effect of bendamustine in wide range of lymphoid malignancies Results from the StiL NHL-1 study published in the Lancet today show that a first-line treatment regimen of bendamustine plus rituximab (B-R) doubles progression-free survival (PFS) compared with the most often used treatment CHOP plus rituximab (CHOP-R), in newly diagnosed patients with indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL). ^ Median PFS for patients treated with B-R was 69.5 months, compared with 31.2 months for patients treated with CHOP-R, the most common chemoimmunotherapy regimen used for the treatment of these diseases (p<0.0001). ^[ ^1 ^] The statistically significant PFS benefit was maintained in the B-R group, regardless of age and across all subtypes; follicular lymphoma, MCL and Waldenström's macroglobulinaemia, with the exception of marginal zone lymphoma, which was non-inferior. ^[ ^1 ^] The results also represent the first time that a simplified treatment regimen has led to a superior complete response (CR) rate compared to CHOP-R in a randomised trial, with 40% of the B-R group achieving a CR compared with 30% for CHOP-R (p=0.021). ^[ ^1 ^] The B-R group also experienced fewer side effects to those receiving CHOP-R, with serious adverse events occurring in 19% of the B-R group compared with 29% for patients receiving CHOP-R. ^[ ^1 ^] Patients receiving B-R experienced less myelosuppression, with severe neutropenia occurring in only 29% of patients compared to 69% with CHOP-R (p<0.0001). ^[ ^1 ^] Infections, a challenging side effect of chemoimmunotherapy, were also significantly reduced with the B-R regimen (p=0.0025). ^[ ^1 ^] A commonly acknowledged side effect of CHOP-R is hair loss; however, hair loss was not reported in a single patient receiving B-R (p<0.0001). ^[ ^1 ^] "These results represent a significant breakthrough in cancer treatment for patients with indolent non-Hodgkin lymphoma and mantle cell lymphoma, who in the past have had to endure particularly aggressive and toxic chemotherapy combinations," said Professor Mathias J. Rummel, Head of the Department for Haematology at the University Hospital in Giessen, Germany, who led the study. "Our study showed bendamustine and rituximab offered a significant improvement in PFS, and that the combination was better tolerated than CHOP-R. This means that the regimen, if approved by the regulatory authorities, could become the new preferred first-line treatment, capable of extending the time patients battling these malignancies live free of disease." "The results of this study are very encouraging for indolent non-Hodgkin lymphoma patients," said Professor John Gribben, Chair of the International Workshop on non-Hodgkin Lymphoma. "The fact that bendamustine and rituximab results in fewer adverse effects with significantly better efficacy than the traditional CHOP-R treatment regimen indicates that this could be a new cornerstone in the treatment of NHL." Non-Hodgkin lymphoma (NHL) is the tenth most common cancer worldwide and figures from 2008 indicate that there are an estimated 356,000 new cases diagnosed every year, comprising two out of five haematological cancers. ^ Indolent lymphomas represent 40% and MCL 3-10% of all NHL subtypes. ^[ ^1 ^] The estimated average incidence of NHL in 2008 in the European Union is 10.8 per 100,000, with the highest estimated incidence being for men living in Luxembourg (around 19 cases per 100,000). ^, ^ Bendamustine is currently licensed as a monotherapy for the treatment of iNHL in patients who have progressed during, or within 6 months following, treatment with rituximab or a rituximab containing regimen. Data from the StiL NHL-1 study have been submitted to regulatory authorities for their consideration of a bendamustine and rituximab combination as a first-line treatment for iNHL and MCL. -Notes to Editors- StiL NHL-1 Study Methodology The StiL NHL-1 study was a prospective, open-label, multi-centre, randomised phase 3 non-inferiority trial, which involved 549 patients aged 18 years or older, with newly diagnosed stage III or IV indolent NHL and MCL. ^[ ^1 ^] Patients were stratified according to histological lymphoma subtype and then randomised to receive bendamustine 90mg/m ^2 on days 1 and 2 of a 4-week cycle or CHOP (3-weekly cycles of cyclophosphamide 750 mg/m ^2 , doxorubicin 50 mg/m ^2 and vincristine 1.4 mg/m ^2 on day 1, and prednisone 100 mg/day for 5 days) for a maximum of 6 cycles. Patients in both treatment arms received rituximab 375 mg/m ^2 on day 1 of each cycle. ^[ ^1 ^] CHOP-R Treatment Regimen Rituximab plus chemotherapy, most commonlyCHOP-R, is the current first-line standard of care for patients with advanced iNHL, and for elderly patients with MCL. ^[ ^1 ^] About Mundipharma The Mundipharma network of independent associated companies consists of privately owned companies and joint ventures covering the world's pharmaceutical markets. These companies are committed to bringing to patients the benefits of pioneering treatment options in the core therapy areas of oncology, pain, respiratory and rheumatoid arthritis. For further information please visit: http://www.mundipharma.com About Bendamustine In 2008 the US Food and Drug Administration (FDA) approved bendamustine for the treatment of iNHL and chronic lymphocytic leukemia (CLL), and it subsequently received European approval in 2010 for certain types of iNHL, CLL and multiple myeloma. Bendamustine has marketing authorisations in Germany, France, UK, Italy, Spain, Austria, Switzerland, Sweden, Norway, Finland, Denmark, Poland, Slovakia, Ireland, Cyprus, Iceland, Belgium, The Netherlands, Greece, Slovenia, Portugal, Czech Republic, Romania and Bulgaria (Levact®, Ribomustin®, Ribovact®) where it is marketed by the Mundipharma network of independent associated companies. Bendamustine is licensed (Levact®, Ribomustin®, Ribovact®) from Astellas Deutschland GmbH. In the United States, bendamustine (TREANDA®) is marketed by Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) and indicated for the treatment of patients with CLL, and indolent B-cell NHL that progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. SymBio Pharmaceuticals Ltd holds exclusive rights to develop and market bendamustine HCL in Japan (sublicensed to Eisai Co Ltd) and selected Asian countries including Hong Kong and Singapore. In South America and Australasia the commercial rights are held by Janssen-Cilag Ltd. References 1. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. The Lancet, 20 February 2013 (online publication, ahead of print). 2. Non-Hodgkin lymphoma incidence statistics: In the EU and worldwide. Cancer Research UK. Available at http://www.cancerresearchuk.org/cancer-info/cancerstats/types/nhl/incidence/#world [ http://www.cancerresearchuk.org/cancer-info/cancerstats/types/nhl/incidence ]. Accessed February 2013 3. European Age-Standardised rates calculated by the Cancer Research UK Statistical Information Team, 2011, using data from GLOBOCAN 2008 v1.2, IARC, version 1.2 [ http://globocan.iarc.fr ]. Available at Non-Hodgkin lymphoma incidence statistics: In the EU and worldwide. Cancer Research UK http://www.cancerresearchuk.org/cancer-info/cancerstats/types/nhl/incidence/#world [ http://www.cancerresearchuk.org/cancer-info/cancerstats/types/nhl/incidence ]. Accessed February 2013. Contact: For further information please contact: Lara Dow, Lara.Dow@mundipharma.co.uk, +44(0)7753-579842. Emma-Fleur Hartley, Emma.Hartley@fleishmaneurope.com, +44(0)20-7395-7114.
Phase 3 Data Published in The Lancet Show Bendamustine (Levact®) Plus Rituximab Doubles Progression-Free Survival in Patients