Data Suggests Treatment with FOLOTYN Reverses Trend of Progressive Resistance Observed in Patients with Drug-Resistant Relapsed or Refractory Peripheral T-Cell Lymphoma
– Results from retrospective analysis of Company's pivotal PROPEL trial –
– Data presented at 11th International Conference on Malignant Lymphoma in Lugano, Switzerland –
LUGANO, Switzerland--(BUSINESS WIRE)--Jun 17, 2011 - 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).
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
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.
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.
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.
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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.
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Posted: June 2011