Phase 3 Data Published in Lancet Show bendamustine (Levact®) Plus Rituximab Doubles Progression-Free Survival in Patients With

 Phase 3 Data Published in 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

  MECHELEN, Belgium, February 20, 2013

MECHELEN, Belgium, 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 anticancer
effect of bendamustine in wide range of lymphoid malignancies

- Bendamustine is currently licensed for use after rituximab, an application
has been made on the basis of this data for first line use.

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). ^[ ^1 ^]

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 treatments 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
randomized trial, with 40% of the B-R group achieving a CR compared with 30.0%
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 could become the new preferred first-line
treatment, capable of extending the time patients battling these malignancies
live free of disease."

Professor Fritz Offner, Head of heamatology at the University of Gent in
Belgium, states : "The treatment of indolent non Hodgkin lymphoma has come a
long way, from an ineffective oral treatment with few side effects to an
immuno-chemotherapy with maintenance antibody treatment that results in median
PFS above 3 years in patients requiring therapy. This has been obtained so far
with chemotherapy that carries significant toxicities, from hair loss to
hospital admissions for neutropenic fever and infections. The current study
from the StiL-group represents a major advance in this field : not only does
bendamustine have significantly lower toxicities, including no hair loss
(which is important for patients continuing to be socially and professionally
active during their treatment) but it also comes with a doubling of PFS,
unseen with any other chemotherapeutic modification of the standard treatment.
This is not only true for the more prevalent follicular NHL but also for other
indolent lymphomas usually absent from major phase 3 trials, such as
Waldenstrom's macroglobulinemia. It is a big step forward for patients to make
cancer care better and less disruptive for daily life."

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. ^[ ^2
^] 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). ^[ ^2 ^] ^- ^[ ^3 ^] 

Bendamustine is currently approved for Indolent non-Hodgkin's lymphomas as
monotherapy in patients, who have progressed during or within 6 months
following treatment with rituximab or a rituximab

containing regimen. Medicinal products should not be used outside their
approved indication.

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, randomized
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.be

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.

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.
Accessed February 2012

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. 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.
Accessed February 2012.

Contact: For further information please contact: Lara Dow,
Lara.Dow@mundipharma.co.uk , +44 (0) 7753 579 842, Michael Magagnin,
Michael.magagnin@mundipharma.be , +32 15 45 11 80