ASH News Daily - Sunday, December 11, 2011 - (Page B-6)

Page B–6 ® ASH NewS DAily Sunday, December 11, 2011 FocuS on early-career hematologiStS 2011 Special Events and Services for Trainees An important part of ASH’s mission is to support education and training in hematology. ASH provides valuable learning opportunities for hematology fellows, residents, medical students, and trainees during this year’s annual meeting. If you are a hematologist in training, plan to attend one or all of these events. Trainee Simultaneous Didactic Sessions During lunch today and Monday, ASH will provide two simultaneous didactic sessions designed to offer trainees an overview of timely and relevant career-oriented issues. A boxed lunch will be provided. Space is available on a first-come, first-served basis. As seating is limited, attendees are strongly encouraged to arrive early. No additional persons will be allowed in the rooms once these sessions are filled. Brief summary of Full Prescribing Information for FOLOTYN® (pralatrexate injection)—Please consult Full Prescribing Information. INDICATIONS AND USAGE FOLOTYN is indicated 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. WARNINGS AND PRECAUTIONS Bone Marrow Suppression FOLOTYN can suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Dose modiﬁcations are based on ANC and platelet count prior to each dose. Mucositis Treatment with FOLOTYN may cause mucositis. If ≥Grade 2 mucositis is observed, omit dose and follow guidelines in Table 1. Dermatologic Reactions FOLOTYN has been associated with severe dermatologic reactions, which may result in death. These dermatologic reactions have been reported in clinical studies (14/663 patients [2.1%]) and post marketing experience, and have included skin exfoliation, ulceration, and toxic epidermal necrolysis (TEN). These reactions may be progressive and increase in severity with further treatment, and may involve skin and subcutaneous sites of known lymphoma. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued. Tumor Lysis Syndrome Tumor lysis syndrome has been reported in patients with lymphoma receiving FOLOTYN. Patients receiving FOLOTYN should be monitored closely and treated for complications. Folic Acid and Vitamin B12 Supplementation Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis. Pregnancy Category D FOLOTYN can cause fetal harm when administered to a pregnant woman. FOLOTYN was embryotoxic and fetotoxic in rats and rabbits. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Decreased Renal Function Although FOLOTYN has not been formally tested in patients with renal impairment, caution is advised when administering FOLOTYN to patients with moderate to severe impairment. Monitor patients for renal function and systemic toxicity due to increased drug exposure. Elevated Liver Enzymes Liver function test abnormalities have been observed after FOLOTYN administration. Persistent liver function test abnormalities may be indicators of liver toxicity and require dose modiﬁcation. Monitor patients for liver function. ADVERSE REACTIONS The most common adverse reactions observed in patients with peripheral t-cell lymphoma (PTCL) treated with FOLOTYN were mucositis, thrombocytopenia, nausea, and fatigue. Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reﬂect the rates observed in practice. The safety of FOLOTYN was evaluated in 111 PTCL patients in a single-arm clinical study in which patients received a starting dose of 30 mg/m2 once weekly for 6 weeks in 7-week cycles. The median duration of treatment was 70 days (range 1-540 days). Most Frequent Adverse Reactions Table 4 summarizes the most frequent adverse reactions, regardless of causality, using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE, version 3.0). Table 4 Adverse Reactions Occurring in PTCL Patients (Incidence ≥10% of patients) N=111 Total Preferred Term Any Adverse Event Mucositisa Thrombocytopeniab Nausea Fatigue Anemia Constipation Pyrexia Edema Cough Epistaxis Vomiting Neutropenia Diarrhea Dyspnea Anorexia Hypokalemia Rash Pruritus N 111 78 45 44 40 38 37 36 33 31 29 28 27 23 21 17 17 17 16 % 100 70 41 40 36 34 33 32 30 28 26 25 24 21 19 15 15 15 14 N 48 19 15 4 5 17 0 1 1 1 0 2 14 2 8 3 4 0 2 Grade 3 % 43 17 14 4 5 15 0 1 1 1 0 2 13 2 7 3 4 0 2 N 34 4 21 0 2 2 0 1 0 0 0 0 8 0 0 0 1 0 0 Grade 4 % 31 4 19b 0 2 2 0 1 0 0 0 0 7 0 0 0 1 0 0 N=111 Total Preferred Term Pain in extremity Back pain Leukopenia Night sweats Asthenia Tachycardia Upper respiratory tract infection a Grade 3 % 12 11 11 11 10 10 10 N 0 3 3 0 1 0 1 % 0 3 3 0 1 0 1 N 0 0 4 0 0 0 0 Grade 4 % 0 0 4 0 0 0 0 N 13 12 12 12 11 11 11 FOLOTYN. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating physician. Based on FOLOTYN’S mechanism of action the prompt administration of leucovorin should be considered. PATIENT COUNSELING INFORMATION See FDA-approved Patient Package Insert. Patients should be instructed to read the Patient Package Insert carefully. DOSAGE AND ADMINISTRATION FOLOTYN should be administered under the supervision of a qualiﬁed physician experienced in the use of antineoplastic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. Peripheral T-cell Lymphoma The recommended dose of FOLOTYN is 30 mg/m2 administered as an intravenous (IV) push over 3-5 minutes via the side port of a free-ﬂowing 0.9% Sodium Chloride Injection, USP IV line once weekly for 6 weeks in 7-week cycles until progressive disease or unacceptable toxicity. Vitamin Supplementation Patients should take low-dose (1.0-1.25 mg) oral folic acid on a daily basis. Folic acid should be initiated during the 10-day period preceding the ﬁrst dose of FOLOTYN, and dosing should continue during the full course of therapy and for 30 days after the last dose of FOLOTYN. Patients should also receive a vitamin B12 (1 mg) intramuscular injection no more than 10 weeks prior to the ﬁrst dose of FOLOTYN and every 8-10 weeks thereafter. Subsequent vitamin B12 injections may be given the same day as treatment with FOLOTYN (see Warnings and Precautions). Monitoring and Dose Modiﬁcations Management of severe or intolerable adverse reactions may require dose omission, reduction, or interruption of FOLOTYN therapy. Monitoring Complete blood cell counts and severity of mucositis should be monitored weekly. Serum chemistry tests, including renal and hepatic function, should be performed prior to the start of the ﬁrst and fourth dose of a given cycle. Dose Modiﬁcation Recommendations Prior to administering any dose of FOLOTYN: • Mucositis should be ≤Grade 1. • Platelet count should be ≥100,000/µL for ﬁrst dose and ≥50,000/µL for all subsequent doses. • Absolute neutrophil count (ANC) should be ≥1,000/µL. Doses may be omitted or reduced based on patient tolerance. Omitted doses will not be made up at the end of the cycle; once a dose reduction occurs for toxicity, do not re-escalate. For dose modiﬁcations and omissions, use the guidelines in Tables 1, 2, and 3. Table 1 FOLOTYN Dose Modiﬁcations for Mucositis Mucositis Gradea on Day of Treatment Grade 2 Grade 2 recurrence Grade 3 Grade 4 a Today 11:15 a.m. - 12:15 p.m. Workforce Issues in Hematology: Where the Jobs Are San Diego Convention Center, Room 31 Linda Burns, MD, University of Minnesota Ethics Misconduct and Research Integrity San Diego Convention Center, Room 33 Nancy Kernan, MD, Memorial Sloan-Kettering Cancer Center Stomatitis or mucosal inﬂammation of the gastrointestinal and genitourinary tracts Five patients with platelets <10,000/µL c Alanine aminotransferase, aspartate aminotransferase, and transaminases increased b Serious Adverse Events Forty-four percent of patients (n=49) experienced a serious adverse event while on study or within 30 days after their last dose of FOLOTYN. The most common serious adverse events (>3%), regardless of causality, were pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. One death from cardiopulmonary arrest in a patient with mucositis and febrile neutropenia was reported in this trial. Deaths from mucositis, febrile neutropenia, sepsis, and pancytopenia occurred in 1.2% of patients treated on all FOLOTYN trials at doses ranging from 30 to 325 mg/m2. Discontinuations Twenty-three percent of patients (n=25) discontinued treatment with FOLOTYN due to adverse reactions. The adverse reactions reported most frequently as the reason for discontinuation of treatment were mucositis (6%, n=7) and thrombocytopenia (5%, n=5). Dose Modiﬁcations The target dose of FOLOTYN was 30 mg/m2 once weekly for 6 weeks in 7-week cycles. The majority of patients (69%, n=77) remained at the target dose for the duration of treatment. Overall, 85% of scheduled doses were administered. Post Marketing Experience Toxic epidermal necrolysis has been identiﬁed during post approval use of FOLOTYN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (see Warnings and Precautions). DRUG INTERACTIONS In vitro studies indicate that pralatrexate is not a substrate, inhibitor, or inducer of CYP450 isoenzymes and has low potential for drug-drug interactions at CYP450 isoenzymes. No formal clinical assessments of pharmacokinetic drug-drug interactions between FOLOTYN and other drugs have been conducted. The effect of co-administration of the uricosuric drug probenecid on pralatrexate pharmacokinetics was investigated in a Phase 1 clinical study. Co-administration of increasing doses of probenecid resulted in delayed clearance of pralatrexate and a commensurate increase in exposure. Due to the contribution of renal excretion (approximately 34%) to the overall clearance of pralatrexate, concomitant administration of drugs that are subject to substantial renal clearance (eg, NSAIDs, trimethoprim/ sulfamethoxazole) may result in delayed clearance of pralatrexate. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category D (see Warnings and Precautions). FOLOTYN can cause fetal harm when administered to a pregnant woman. Pralatrexate was embryotoxic and fetotoxic in rats at IV doses of 0.06 mg/kg/ day (0.36 mg/m2/day or about 1.2% of the clinical dose on a mg/m2 basis) given on gestation days 7 through 20. Treatment with pralatrexate caused a dose-dependent decrease in fetal viability manifested as an increase in late, early, and total resorptions. There was also a dose-dependent increase in post-implantation loss. In rabbits, IV doses of 0.03 mg/kg/day (0.36 mg/ m2/day) or greater given on gestation days 8 through 21 also caused abortion and fetal lethality. This toxicity manifested as early and total resorptions, post-implantation loss, and a decrease in the total number of live fetuses. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Nursing Mothers It is not known whether pralatrexate is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from this drug, a decision should be made whether to discontinue nursing or to discontinue FOLOTYN, taking into account the importance of FOLOTYN to the mother. Pediatric Use Pediatric patients were not included in clinical studies with FOLOTYN. The safety and effectiveness of FOLOTYN in pediatric patients have not been established. Geriatric Use In the PTCL efﬁcacy study, 36% of patients (n=40) were 65 years of age and over. No overall differences in efﬁcacy and safety were observed in patients based on age (<65 years compared with ≥65 years). No dosage adjustment is required in elderly patients with normal renal function. Hepatic Impairment Formal studies have not been performed with FOLOTYN in patients with hepatic impairment. Patients with the following laboratory values were excluded from the pralatrexate lymphoma clinical trials: total bilirubin >1.5 mg/dL; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN); and AST or ALT >5 × ULN if documented hepatic involvement with lymphoma. Renal Impairment See Warnings and Precautions. OVERDOSAGE No speciﬁc information is available on the treatment of overdosage of Monday, December 12 12:15 - 1:15 p.m. Drug Development – Bench to Bedside and Beyond San Diego Convention Center, Room 31 John Leonard, MD, Cornell University How to Publish a Manuscript in a Peer-Reviewed Journal San Diego Convention Center, Room 33 Cindy Dunbar, MD, Editor in-Chief, Blood Trainee Lounge San Diego Convention Center, Sails Pavilion, Upper Level The lounge provides a relaxing place for trainees to meet with colleagues, access the Internet, and recharge with complimentary refreshments. Trainee Lounge Hours Sunday and Monday: 7:00 a.m. 6:00 p.m. Tuesday: 7:00 a.m. - 12:00 noon Action Omit dose Omit dose Omit dose Stop therapy Dose upon Recovery to ≤Grade 1 Continue prior dose 20 mg/m2 20 mg/m2 Per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE, Version 3.0) Table 2 FOLOTYN Dose Modiﬁcations for Hematologic Toxicities Blood Count on Day of Treatment Platelet <50,000/µL Duration of Toxicity 1 week 2 weeks 3 weeks Action Omit dose Omit dose Stop therapy Omit dose Omit dose, give G-CSF or GM-CSF support Omit dose, give G-CSF or GM-CSF support Stop therapy Continue prior dose Continue prior dose with G-CSF or GM-CSF support 20 mg/m2 with G-CSF or GM-CSF support Dose upon Restart Continue prior dose 20 mg/m2 ANC 500-1,000/µL 1 week and no fever 1 week ANC 500-1,000/µL with fever 2 weeks or or recurrence ANC <500/µL 3 weeks or 2nd recurrence Table 3 FOLOTYN Dose Modiﬁcations for All Other Treatment-related Toxicities Toxicity Gradea on Day of Treatment Grade 3 Grade 4 a Action Omit dose Stop therapy Dose upon Recovery to ≤Grade 2 20 mg/m2 Per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE, Version 3.0) Manufactured for: Allos Therapeutics, Inc. Westminster, CO 80020 1-888-ALLOS88 (1-888-255-6788) FOLOTYN, ALLOS, and the mobius triangle symbol are all registered trademarks of Allos Therapeutics, Inc. U.S. Patent: 6,028,071 and 7,622,470 Rev.3: January 2011 © 2011 Allos Therapeutics, Inc. All rights reserved. Recycle Abstract and Program Books If you will be disposing of your Abstract Book, Program Book, or any other paper materials, please be sure to recycle them. Throughout the convention center there are clearly marked, bright blue recycling bins for your convenience. Thank you for helping ASH lessen its carbon footprint. ALL-11-0506_FOL-1184-11_ASH-Brf-Sum.indd 1 10/19/11 1:13 PM

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ASH News Daily - Sunday, December 11, 2011

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