Allos Therapeutics, Inc. (NASDAQ: ALTH) today reported results
from a retrospective analysis of data from the Company’s pivotal
PROPEL trial which suggested that treatment with single-agent
FOLOTYN® (pralatrexate injection) may result in increased response
rates and progression-free survival relative to the immediate prior
line of therapy in patients with relapsed or refractory peripheral
T-cell lymphoma (PTCL). The analysis assessed those patients
enrolled in the PROPEL trial who had received two or more lines of
therapy prior to enrolling in the study and receiving FOLOTYN. Data
were presented at the 11th International Conference on Malignant
Lymphoma (ICML) in Lugano, Switzerland (June 15-18).
The authors described a pattern of ‘progressive resistance’ as a
continual decrease of responses and progression-free survival in
patients in the second-line treatment setting and then with each
subsequent therapy – a pattern often observed in hematologic
malignancies and solid tumors.
“This analysis not only provides insight into the occurrence of
progressive resistance in the treatment of patients with peripheral
T-cell lymphoma, but also suggests that FOLOTYN may reverse the
pattern of progressive resistance observed in patients with
relapsed or refractory peripheral T-cell lymphoma,” said Charles
Morris, MB ChB, MRCP, chief medical officer at Allos
Therapeutics.
PROPEL enrolled 115 patients, 109 of whom were considered
evaluable for efficacy according to the trial protocol. Study
endpoints included overall response rate – defined as complete
response, unconfirmed complete response, and partial response – as
well as duration of response, progression-free survival, and
overall survival. Patients enrolled in PROPEL had a median of three
prior systemic therapies.
As previously reported, this analysis was conducted to determine
whether a trend of progressive resistance is observed in patients
with relapsed or refractory PTCL, as well as to identify the
efficacy of FOLOTYN as a subsequent therapy compared to previous
treatments in patients enrolled in the PROPEL trial – thus
assessing the potential ability of FOLOTYN to overcome progressive
drug resistance.
Analysis of the historical data available for patients –
including prior treatments received and responses observed – showed
a decrease in overall response rate and progression-free survival
with each sequential treatment received prior to enrolling in
PROPEL and receiving FOLOTYN:
- In patients who received three or more
lines of therapy prior to enrolling in PROPEL (n=57), response
rates decreased from 56 percent (32 of 57 patients) to 30 percent
(17 of 57 patients); median progression-free survival decreased
from 213.5 days to 95 days.
- In patients who received two or more
lines of therapy prior to enrolling in PROPEL (n=86), response
rates decreased from 38 percent (33 of 86 patients) to 29 percent
(25 of 86 patients); median progression-free survival decreased
from 144 days to 89.5 days.
Following treatment with FOLOTYN, response rates and
progression-free survival increased relative to the previous line
of therapy:
- In patients who received three or more
prior therapies, response rates increased from 30 percent (17 of 57
patients) to 40 percent (23 of 57 patients); median
progression-free survival increased from 95 days to 134 days.
- In patients who received two or more
prior therapies, response rates increased from 29 percent (25 of 86
patients) to 40 percent (34 of 86 patients); median
progression-free survival increased from 89.5 days to 119
days.
Analysis of the overall patient population, all of whom received
one or more lines of therapy prior to enrolling in PROPEL, showed a
response rate of 38 percent (41 of 109 patients) with the most
recent prior therapy and 39 percent (43 of 109 patients) with
FOLOTYN treatment; median progression-free survival increased from
114 days with the most recent prior therapy to 121 days with
FOLOTYN treatment.
Details of safety and adverse events have been reported
previously. Mucositis (Grade 3-4) was one of the most common
adverse events; twenty-five patients (23%) had their dose reduced
due to mucositis. Other common Grade 3-4 adverse events were
thrombocytopenia, neutropenia, anemia, and dyspnea. Fifty patients
(45%) experienced serious adverse events; most common serious AEs
were pyrexia (7%), mucositis (5%), febrile neutropenia (5%), sepsis
(5%), dehydration (4%), and dyspnea (4%).
FOLOTYN, a folate analogue metabolic inhibitor, is the only drug
approved in the U.S. for the treatment of patients with relapsed or
refractory peripheral T-cell lymphoma (PTCL). This indication is
based on overall response rate. Clinical benefit such as
improvement in progression-free survival or overall survival has
not been demonstrated. In December 2010, Allos announced that the
Company’s Marketing Authorisation Application (MAA), seeking
approval of FOLOTYN for the treatment of patients with relapsed or
refractory PTCL, was accepted for review by the European Medicines
Agency (EMA).
About PROPEL
PROPEL (Pralatrexate in Patients with Relapsed
or Refractory Peripheral T-Cell Lymphoma), an
open-label, single-arm, multicenter, international Phase 2 clinical
trial, enrolled 115 patients with relapsed or refractory PTCL, 109
of whom were considered evaluable for efficacy according to the
trial protocol. Patients were considered evaluable if they received
at least one dose of FOLOTYN, their diagnosis of PTCL was confirmed
by independent pathology review, and they had relapsed or
refractory disease after at least one prior treatment. Patients
enrolled in PROPEL had received a median of three prior systemic
therapies. Prior treatments included multi-agent chemotherapy,
single-agent chemotherapy, stem cell transplant, investigational
agents or steroids alone. Patients were treated with FOLOTYN at 30
mg/m2 once weekly by IV push over 3-5 minutes for 6 weeks in 7-week
cycles until disease progression or unacceptable toxicity. In
addition, patients received 1mg of vitamin B12 intramuscularly
every 8-10 weeks and 1.0-1.25 mg of folic acid orally on a daily
basis.
The primary efficacy endpoint was overall response rate (ORR) –
defined as complete response (CR), unconfirmed complete responses
(CRu), and partial response (PR) – as assessed by International
Workshop Criteria (IWC). The key secondary efficacy endpoint was
duration of response. Response assessments were scheduled at the
end of cycle 1 and then every other cycle (every 14 weeks).
Duration of response was measured from the first day of documented
response to disease progression or death. Response and disease
progression were evaluated by independent central review using the
IWC.
An updated analysis of data from PROPEL was recently published
in the March 20, 2011 issue of the Journal of Clinical
Oncology.
About Peripheral T-Cell Lymphoma
Peripheral T-cell lymphomas are a biologically diverse group of
aggressive, mature T and NK (natural killer) cell non-Hodgkin
lymphomas with similar outcomes, which include PTCL-NOS (PTCL not
otherwise specified), AITL (angioimmunoblastic T-cell lymphoma),
and ALCL (anaplastic large-cell lymphoma).1 The prognosis for
patients with PTCL is generally poor for most subtypes.2
T-cell lymphomas account for approximately 10% to 15% of all
cases of non-Hodgkin lymphomas (NHL).1-3 Allos estimates the
current annual incidence of PTCL to be approximately 5,900 patients
in the U.S. and approximately 6,000-7,000 patients in the top five
European markets. The majority of patients ultimately have
refractory disease to a variety of agents, including multi-agent
chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine,
and prednisone) or CHOP-like regimens. The 5-year overall survival
rate in these patients is 25% to 40%, depending on sub-type.4-5
About FOLOTYN
FOLOTYN, a folate analogue metabolic inhibitor, was discovered
by Sloan-Kettering Institute for Cancer Research, SRI International
and Southern Research Institute and developed by Allos
Therapeutics. In September 2009, the U.S. Food and Drug
Administration (FDA) granted accelerated approval for FOLOTYN for
use as a single agent for the treatment of patients with relapsed
or refractory PTCL. This indication is based on overall response
rate. Clinical benefit such as improvement in progression free
survival or overall survival has not been demonstrated. FOLOTYN has
been available to patients in the U.S. since October 2009.
About Allos Therapeutics
Allos Therapeutics, Inc. (Nasdaq: ALTH) is a biopharmaceutical
company committed to the development and commercialization of
innovative anti-cancer therapeutics. Allos is currently focused on
the development and commercialization of FOLOTYN® (pralatrexate
injection), a folate analogue metabolic inhibitor. FOLOTYN is
approved in the U.S. for the treatment of patients with relapsed or
refractory PTCL. Allos is also developing FOLOTYN in other
hematologic malignancies and solid tumors. For additional
information, please visit www.allos.com.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
FOLOTYN may suppress bone marrow function, manifested by
thrombocytopenia, neutropenia, and anemia. Monitor blood counts and
omit or modify dose for hematologic toxicities.
Mucositis may occur. If ≥Grade 2 mucositis is observed, omit or
modify dose. Patients should be instructed to take folic acid and
receive vitamin B12 to potentially reduce treatment-related
hematological toxicity and mucositis.
Fatal dermatologic reactions may occur. Dermatologic reactions
may be progressive and increase in severity with further treatment.
Patients with dermatologic reactions should be monitored closely,
and if severe, FOLOTYN should be withheld or discontinued.
Tumor lysis syndrome may occur. Monitor patients and treat if
needed.
FOLOTYN can cause fetal harm. Women should avoid becoming
pregnant while being treated with FOLOTYN and pregnant women should
be informed of the potential harm to the fetus.
Use caution and monitor patients when administering FOLOTYN to
patients with moderate to severe renal function impairment.
Elevated liver function test abnormalities may occur and require
monitoring. If liver function test abnormalities are ≥Grade 3, omit
or modify dose.
Adverse Reactions
The most common adverse reactions were mucositis (70%),
thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most
common serious adverse events are pyrexia, mucositis, sepsis,
febrile neutropenia, dehydration, dyspnea, and
thrombocytopenia.
Use in Specific Patient Population
Nursing mothers should be advised to discontinue nursing or the
drug, taking into consideration the importance of the drug to the
mother.
Drug Interactions
Co-administration of drugs subject to renal clearance (e.g.,
probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result
in delayed renal clearance.
Please see FOLOTYN Full Prescribing Information at
www.FOLOTYN.com.
Safe Harbor Statement
This press release contains forward-looking statements that are
made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995. Such forward-looking
statements include statements regarding the potential of FOLOTYN to
reverse the pattern of drug resistance in patients with relapsed or
refractory PTCL; and other statements that are other than
statements of historical facts. In some cases, you can identify
forward-looking statements by terminology such as “may,” “will,”
“should,” “expects,” “intends,” “plans,” anticipates,” “believes,”
“estimates,” “predicts,” “projects,” “potential,” “continue,” and
other similar terminology or the negative of these terms, but their
absence does not mean that a particular statement is not
forward-looking. Such forward-looking statements are not guarantees
of future performance and are subject to risks and uncertainties
that may cause actual results to differ materially from those
anticipated by the forward-looking statements. Additional
information concerning these risks and uncertainties is contained
in the "Risk Factors" section of the Company's Quarterly Report on
Form 10-Q for the quarter ended March 31, 2011, and in the
Company's other periodic reports and filings with the Securities
and Exchange Commission. The Company cautions investors not to
place undue reliance on the forward-looking statements contained in
this press release. All forward-looking statements are based on
information currently available to the Company on the date hereof,
and the Company undertakes no obligation to revise or update these
forward-looking statements to reflect events or circumstances after
the date of this presentation, except as required by law.
Note: The Allos logo and FOLOTYN name are trademarks of Allos
Therapeutics, Inc.
Source: Allos Therapeutics, Inc.
References:
1. The Non-Hodgkin's Lymphoma Classification Project. A clinical
evaluation of the International Lymphoma Study Group classification
of non-Hodgkin's lymphoma. Blood. 1997;89 (11):3909-3908.2.
Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update
[review]. Lancet Oncol. 2004;5(6):341-353.3. O'Leary HM, Savage KJ.
Novel therapies in peripheral T-cell lymphomas [review]. Curr Oncol
Rep. 2008;134(5):202-207.4. Savage KJ, Chhanabhai M, Gascoyne RD,
et al. Characterization of peripheral T-cell lymphomas in a single
North American institution by the WHO classification. Ann Oncol
2004;15(10):1467-75.5. Savage KJ. Peripheral T-cell Lymphomas.
Blood Rev. 2007; 21:201-216.
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