INDICATIONS
BELEODAQ IS INDICATED FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA (PTCL).
THIS INDICATION IS APPROVED UNDER ACCELERATED APPROVAL BASED ON TUMOR RESPONSE RATE AND DURATION OF RESPONSE [SEE CLINICAL STUDIES]. AN IMPROVEMENT IN SURVIVAL OR DISEASE-RELATED SYMPTOMS HAS NOT BEEN ESTABLISHED. CONTINUED APPROVAL FOR THIS INDICATION MAY BE CONTINGENT UPON VERIFICATION AND DESCRIPTION OF CLINICAL BENEFIT IN THE CONFIRMATORY TRIAL.
SIDE EFFECTS
THE FOLLOWING SERIOUS ADVERSE REACTIONS ARE DESCRIBED IN MORE DETAIL IN OTHER SECTIONS OF THE PRESCRIBING INFORMATION.
" HEMATOLOGIC TOXICITY [SEE WARNINGS AND PRECAUTIONS]
" INFECTION [SEE WARNINGS AND PRECAUTIONS]
" HEPATOTOXICITY [SEE WARNINGS AND PRECAUTIONS]
" TUMOR LYSIS SYNDROME [SEE WARNINGS AND PRECAUTIONS]
" GASTROINTESTINAL TOXICITY [SEE WARNINGS AND PRECAUTIONS]
THE MOST COMMON ADVERSE REACTIONS OBSERVED IN THE TRIAL OF PATIENTS WITH RELAPSED OR REFRACTORY PTCL TREATED WITH BELEODAQ WERE NAUSEA, FATIGUE, PYREXIA, ANEMIA, AND VOMITING [SEE CLINICAL STUDIES].
CLINICAL TRIALS EXPERIENCE
BECAUSE CLINICAL TRIALS ARE CONDUCTED UNDER WIDELY VARYING CONDITIONS, ADVERSE REACTION RATES OBSERVED IN THE CLINICAL TRIALS OF BELEODAQ MAY NOT REFLECT THE RATES OBSERVED IN PRACTICE.
ADVERSE REACTIONS IN PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA
THE SAFETY OF BELEODAQ WAS EVALUATED IN 129 PATIENTS WITH RELAPSED OR REFRACTORY PTCL IN THE SINGLE ARM CLINICAL TRIAL IN WHICH PATIENTS WERE ADMINISTERED BELEODAQ AT A DOSAGE OF 1,000 MG/M² ADMINISTERED OVER 30 MINUTES BY IV INFUSION ONCE DAILY ON DAYS 1-5 OF A 21-DAY CYCLE [SEE CLINICAL STUDIES]. THE MEDIAN DURATION OF TREATMENT WAS 2 CYCLES (RANGE 1 - 33 CYCLES).
TABLE 2 SUMMARIZES THE ADVERSE REACTIONS REGARDLESS OF CAUSALITY FROM THE TRIAL IN PATIENTS WITH RELAPSED OR REFRACTORY PTCL.
TABLE 2: ADVERSE REACTIONS OCCURRING IN ? 10% OF PATIENTS BY PREFERRED TERM AND SEVERITY IN PATIENTS WITH RELAPSED OR REFRACTORY PTCL (NCI-CTC GRADE 1-4)
MEDDRA PREFERRED TERM PERCENTAGE OF PATIENTS (%)
(N=129)
ALL GRADES GRADE 3 OR 4
ALL ADVERSE REACTIONS 97 61
NAUSEA 42 1
FATIGUE 37 5
PYREXIA 35 2
ANEMIA 32 11
VOMITING 29 1
CONSTIPATION 23 1
DIARRHEA 23 2
DYSPNEA 22 6
RASH 20 1
PERIPHERAL EDEMA 20 0
COUGH 19 0
THROMBOCYTOPENIA 16 7
PRURITUS 16 3
CHILLS 16 1
INCREASED BLOOD LACTATE DEHYDROGENASE 16 2
DECREASED APPETITE 15 2
HEADACHE 15 0
INFUSION SITE PAIN 14 0
HYPOKALEMIA 12 4
PROLONGED QT 11 4
ABDOMINAL PAIN 11 1
HYPOTENSION 10 3
PHLEBITIS 10 1
DIZZINESS 10 0
NOTE: ADVERSE REACTIONS ARE LISTED BY ORDER OF INCIDENCE IN THE "ALL GRADES" CATEGORY FIRST, THEN BY INCIDENCE IN " THE GRADE 3 OR 4" CATEGORY; MEDDRA = MEDICAL DICTIONARY FOR REGULATORY ACTIVITIES; SEVERITY MEASURED BY NATIONAL CANCER INSTITUTE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (NCI-CTCAE) VERSION 3.0
SERIOUS ADVERSE REACTIONS
SIXTY-ONE PATIENTS (47.3%) EXPERIENCED SERIOUS ADVERSE REACTIONS WHILE TAKING BELEODAQ OR WITHIN 30 DAYS AFTER THEIR LAST DOSE OF BELEODAQ . THE MOST COMMON SERIOUS ADVERSE REACTIONS ( > 2%) WERE PNEUMONIA, PYREXIA, INFECTION, ANEMIA, INCREASED CREATININE, THROMBOCYTOPENIA, AND MULTI-ORGAN FAILURE. ONE TREATMENT-RELATED DEATH ASSOCIATED WITH HEPATIC FAILURE WAS REPORTED IN THE TRIAL.
ONE PATIENT WITH BASELINE HYPERURICEMIA AND BULKY DISEASE EXPERIENCED GRADE 4 TUMOR LYSIS SYNDROME DURING THE FIRST CYCLE OF TREATMENT AND DIED DUE TO MULTI-ORGAN FAILURE. A TREATMENT-RELATED DEATH FROM VENTRICULAR FIBRILLATION WAS REPORTED IN ANOTHER MONOTHERAPY CLINICAL TRIAL WITH BELEODAQ. ECG ANALYSIS DID NOT IDENTIFY QTC PROLONGATION.
DISCONTINUATIONS DUE TO ADVERSE REACTIONS
TWENTY-FIVE PATIENTS (19.4%) DISCONTINUED TREATMENT WITH BELEODAQ DUE TO ADVERSE REACTIONS. THE ADVERSE REACTIONS REPORTED MOST FREQUENTLY AS THE REASON FOR DISCONTINUATION OF TREATMENT INCLUDED ANEMIA, FEBRILE NEUTROPENIA, FATIGUE, AND MULTI-ORGAN FAILURE.
DOSAGE MODIFICATIONS DUE TO ADVERSE REACTIONS
IN THE TRIAL, DOSAGE ADJUSTMENTS DUE TO ADVERSE REACTIONS OCCURRED IN 12% OF BELEODAQ-TREATED PATIENTS.
READ THE BELEODAQ (BELINOSTAT FOR INJECTION FOR INTRAVENOUS USE) SIDE EFFECTS CENTER FOR A COMPLETE GUIDE TO POSSIBLE SIDE EFFECTS
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS
FOR INJECTION: 500 MG, LYOPHILIZED POWDER IN SINGLE-USE VIAL FOR RECONSTITUTION
BELEODAQ (BELINOSTAT) FOR INJECTION IS SUPPLIED IN SINGLE VIAL CARTONS; EACH 30 ML CLEAR VIAL CONTAINS STERILE, LYOPHILIZED POWDER EQUIVALENT TO 500 MG BELINOSTAT.
NDC 68152-108-09: INDIVIDUAL CARTON OF BELEODAQ 30 ML SINGLE-USE VIAL CONTAINING 500 MG BELINOSTAT.
STORAGE AND HANDLING
STORE BELEODAQ (BELINOSTAT) FOR INJECTION AT ROOM TEMPERATURE 20°C TO 25°C (68°C TO 77°F). EXCURSIONS ARE PERMITTED BETWEEN 15°C AND 30°C (59°F AND 86°F). RETAIN IN ORIGINAL PACKAGE UNTIL USE. [SEE USP CONTROLLED ROOM TEMPERATURE].
BELEODAQ IS A CYTOTOXIC DRUG. FOLLOW SPECIAL HANDLING AND DISPOSAL PROCEDURES [SEE REFERENCES1].
REFERENCES
1 OSHA HAZARDOUS DRUGS. OSHA. [ACCESSED ON 14 MAY 2014, FROM HTTP://WWW.OSHA.GOV/SLTC/HAZARDOUSDRUGS/INDEX.HTML].
MANUFACTURED FOR: SPECTRUM PHARMACEUTICALS, INC. IRVINE, CA 92618. ISSUED: JULY 2014
DOSAGE AND ADMINISTRATION
DOSING INFORMATION
THE RECOMMENDED DOSAGE OF BELEODAQ IS 1,000 MG/M² ADMINISTERED OVER 30 MINUTES BY INTRAVENOUS INFUSION ONCE DAILY ON DAYS 1-5 OF A 21-DAY CYCLE. CYCLES CAN BE REPEATED EVERY 21 DAYS UNTIL DISEASE PROGRESSION OR UNACCEPTABLE TOXICITY.
DOSAGE MODIFICATION FOR HEMATOLOGIC AND NON-HEMATOLOGIC TOXICITIES
TABLE 1 DISPLAYS THE RECOMMENDED BELEODAQ DOSAGE MODIFICATIONS FOR HEMATOLOGIC AND NON-HEMATOLOGIC TOXICITIES. BASE DOSAGE ADJUSTMENTS FOR THROMBOCYTOPENIA AND NEUTROPENIA ON PLATELET AND ABSOLUTE NEUTROPHIL NADIR (LOWEST VALUE) COUNTS IN THE PRECEDING CYCLE OF THERAPY.
" ABSOLUTE NEUTROPHIL COUNT (ANC) SHOULD BE GREATER THAN OR EQUAL TO 1.0 X 109/L AND THE PLATELET COUNT SHOULD BE GREATER THAN OR EQUAL TO 50 X 109/L PRIOR TO THE START OF EACH CYCLE AND PRIOR TO RESUMING TREATMENT FOLLOWING TOXICITY. RESUME SUBSEQUENT TREATMENT WITH BELEODAQ ACCORDING TO THE GUIDELINES DESCRIBED IN TABLE 1 BELOW. DISCONTINUE BELEODAQ IN PATIENTS WHO HAVE RECURRENT ANC NADIRS LESS THAN 0.5 X 109/L AND/OR RECURRENT PLATELET COUNT NADIRS LESS THAN 25 X 109/L AFTER TWO DOSAGE REDUCTIONS.
" OTHER TOXICITIES MUST BE NCI-CTCAE GRADE 2 OR LESS PRIOR TO RE-TREATMENT.
MONITOR COMPLETE BLOOD COUNTS AT BASELINE AND WEEKLY. PERFORM SERUM CHEMISTRY TESTS, INCLUDING RENAL AND HEPATIC FUNCTIONS PRIOR TO THE START OF THE FIRST DOSE OF EACH CYCLE.
TABLE 1: DOSAGE MODIFICATIONS FOR HEMATOLOGIC AND NON-HEMATOLOGIC TOXICITIES
DOSAGE MODIFICATION
DOSAGE MODIFICATIONS DUE TO HEMATOLOGIC TOXICITIES
PLATELET COUNT ? 25 X 109/L AND NADIR ANC ? 0.5 X 109/L NO CHANGE
NADIR ANC < 0.5 X 109/L (ANY PLATELET COUNT) DECREASE DOSAGE BY 25% (750 MG/M2)
PLATELET COUNT < 25 X 109/L (ANY NADIR ANC)
DOSAGE MODIFICATIONS DUE TO NON-HEMATOLOGIC TOXICITIES
ANY CTCAE GRADE 3 OR 4 ADVERSE REACTIONA DECREASE DOSAGE BY 25% (750 MG/M2)
RECURRENCE OF CTCAE GRADE 3 OR 4 ADVERSE REACTION AFTER TWO DOSAGE REDUCTIONS DISCONTINUE BELEODAQ
AFOR NAUSEA, VOMITING, AND DIARRHEA, ONLY DOSE MODIFY IF THE DURATION IS GREATER THAN 7 DAYS WITH SUPPORTIVE MANAGEMENT
PATIENTS WITH REDUCED UGT1A1 ACTIVITY
REDUCE THE STARTING DOSE OF BELEODAQ TO 750 MG/M² IN PATIENTS KNOWN TO BE HOMOZYGOUS FOR THE UGT1A1*28 ALLELE [SEE CLINICAL PHARMACOLOGY].
PREPARATION AND ADMINISTRATION PRECAUTIONS
AS WITH OTHER POTENTIALLY CYTOTOXIC ANTICANCER AGENTS, EXERCISE CARE IN THE HANDLING AND PREPARATION OF SOLUTIONS PREPARED WITH BELEODAQ.
RECONSTITUTION AND INFUSION INSTRUCTIONS
a. ASEPTICALLY RECONSTITUTE EACH VIAL OF BELEODAQ BY ADDING 9 ML OF STERILE WATER FOR INJECTION, USP, INTO THE BELEODAQ VIAL WITH A SUITABLE SYRINGE TO ACHIEVE A CONCENTRATION OF 50 MG OF BELINOSTAT PER ML. SWIRL THE CONTENTS OF THE VIAL UNTIL THERE ARE NO VISIBLE PARTICLES IN THE RESULTING SOLUTION. THE RECONSTITUTED PRODUCT MAY BE STORED FOR UP TO 12 HOURS AT AMBIENT TEMPERATURE (15-25°C; 59-77°F).
b. ASEPTICALLY WITHDRAW THE VOLUME NEEDED FOR THE REQUIRED DOSAGE (BASED ON THE 50 MG/ML CONCENTRATION AND THE PATIENT'S BSA [M²]) AND TRANSFER TO AN INFUSION BAG CONTAINING 250 ML OF 0.9 % SODIUM CHLORIDE INJECTION. THE INFUSION BAG WITH DRUG SOLUTION MAY BE STORED AT AMBIENT ROOM TEMPERATURE (15-25°C; 59-77°F) FOR UP TO 36 HOURS INCLUDING INFUSION TIME.
c. VISUALLY INSPECT THE SOLUTION FOR PARTICULATE MATTER. DO NOT USE IF CLOUDINESS OR PARTICULATES ARE OBSERVED.
d. CONNECT THE INFUSION BAG CONTAINING DRUG SOLUTION TO AN INFUSION SET WITH A 0.22 ?M IN-LINE FILTER FOR ADMINISTRATION.
e. INFUSE INTRAVENOUSLY OVER 30 MINUTES. IF INFUSION SITE PAIN OR OTHER SYMPTOMS POTENTIALLY ATTRIBUTABLE TO THE INFUSION OCCUR, THE INFUSION TIME MAY BE EXTENDED TO 45 MINUTES.
OVERDOSE
NO SPECIFIC INFORMATION IS AVAILABLE ON THE TREATMENT OF OVERDOSAGE OF BELEODAQ. THERE IS NO ANTIDOTE FOR BELEODAQ AND IT IS NOT KNOWN IF BELEODAQ IS DIALYZABLE. IF AN OVERDOSE OCCURS, GENERAL SUPPORTIVE MEASURES SHOULD BE INSTITUTED AS DEEMED NECESSARY BY THE TREATING PHYSICIAN. THE ELIMINATION HALF-LIFE OF BELINOSTAT IS 1.1 HOURS [SEE CLINICAL PHARMACOLOGY].
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
BELEODAQ IS A HISTONE DEACETYLASE (HDAC) INHIBITOR. HDACS CATALYZE THE REMOVAL OF ACETYL GROUPS FROM THE LYSINE RESIDUES OF HISTONES AND SOME NON-HISTONE PROTEINS. IN VITRO, BELINOSTAT CAUSED THE ACCUMULATION OF ACETYLATED HISTONES AND OTHER PROTEINS, INDUCING CELL CYCLE ARREST AND/OR APOPTOSIS OF SOME TRANSFORMED CELLS. BELINOSTAT SHOWS PREFERENTIAL CYTOTOXICITY TOWARDS TUMOR CELLS COMPARED TO NORMAL CELLS. BELINOSTAT INHIBITED THE ENZYMATIC ACTIVITY OF HISTONE DEACETYLASES AT NANOMOLAR CONCENTRATIONS ( < 250 NM).
PHARMACODYNAMICS
CARDIAC ELECTROPHYSIOLOGY
MULTIPLE CLINICAL TRIALS HAVE BEEN CONDUCTED WITH BELEODAQ, IN MANY OF WHICH ECG DATA WERE COLLECTED AND ANALYZED BY A CENTRAL LABORATORY. ANALYSIS OF CLINICAL ECG AND BELINOSTAT PLASMA CONCENTRATION DATA DEMONSTRATED NO MEANINGFUL EFFECT OF BELEODAQ ON CARDIAC REPOLARIZATION. NONE OF THE TRIALS SHOWED ANY CLINICALLY RELEVANT CHANGES CAUSED BY BELEODAQ ON HEART RATE, PR DURATION OR QRS DURATION AS MEASURES OF AUTONOMIC STATE, ATRIO-VENTRICULAR CONDUCTION OR DEPOLARIZATION; THERE WERE NO CASES OF TORSADES DE POINTES.
PHARMACOKINETICS
THE PHARMACOKINETIC CHARACTERISTICS OF BELINOSTAT WERE ANALYZED FROM POOLED DATA FROM PHASE ½ CLINICAL STUDIES THAT USED DOSES OF BELINOSTAT RANGING FROM 150 TO 1200 MG/M². THE TOTAL MEAN PLASMA CLEARANCE AND ELIMINATION HALF-LIFE WERE 1240 ML/MIN AND 1.1 HOURS, RESPECTIVELY. THE TOTAL CLEARANCE APPROXIMATES AVERAGE HEPATIC BLOOD FLOW (1500 ML/MIN), SUGGESTING HIGH HEPATIC EXTRACTION (CLEARANCE BEING FLOW DEPENDENT).
DISTRIBUTION
THE MEAN BELINOSTAT VOLUME OF DISTRIBUTION APPROACHES TOTAL BODY WATER, INDICATING THAT BELINOSTAT HAS LIMITED BODY TISSUE DISTRIBUTION. IN VITRO PLASMA STUDIES HAVE SHOWN THAT BETWEEN 92.9% AND 95.8% OF BELINOSTAT IS BOUND TO PROTEIN IN AN EQUILIBRIUM DIALYSIS ASSAY, AND WAS INDEPENDENT OF BELINOSTAT PLASMA CONCENTRATIONS FROM 500 TO 25,000 NG/ML.
METABOLISM
BELINOSTAT IS PRIMARILY METABOLIZED BY HEPATIC UGT1A1. STRONG UGT1A1 INHIBITORS ARE EXPECTED TO INCREASE EXPOSURE TO BELINOSTAT. BELINOSTAT ALSO UNDERGOES HEPATIC METABOLISM BY CYP2A6, CYP2C9, AND CYP3A4 ENZYMES TO FORM BELINOSTAT AMIDE AND BELINOSTAT ACID. THE ENZYMES RESPONSIBLE FOR THE FORMATION OF METHYL BELINOSTAT AND 3-(ANILINOSULFONYL)-BENZENECARBOXYLIC ACID, ( 3-ASBA) ARE NOT KNOWN.
EXCRETION
BELINOSTAT IS ELIMINATED PREDOMINANTLY THROUGH METABOLISM WITH LESS THAN 2% OF THE DOSE RECOVERED UNCHANGED IN URINE. ALL MAJOR HUMAN METABOLITES (METHYL BELINOSTAT, BELINOSTAT AMIDE, BELINOSTAT ACID, BELINOSTAT GLUCURONIDE, AND 3-ASBA) ARE GENERALLY EXCRETED IN URINE WITHIN THE FIRST 24 HOURS AFTER DOSE ADMINISTRATION. METABOLITES 3-ASBA AND BELINOSTAT GLUCURONIDE REPRESENTED THE HIGHEST FRACTIONS OF THE BELINOSTAT DOSE EXCRETED IN URINE (4.61% AND 30.5%, RESPECTIVELY).
DRUG-DRUG INTERACTIONS
IN VITRO STUDIES SHOWED BELINOSTAT AND ITS METABOLITES (INCLUDING BELINOSTAT GLUCURONIDE, BELINOSTAT AMIDE, METHYL BELINOSTAT) INHIBITED METABOLIC ACTIVITIES OF CYP2C8 AND CYP2C9. OTHER METABOLITES (3-ASBA AND BELINOSTAT ACID) INHIBITED CYP2C8.
IN CANCER PATIENTS, CO-ADMINISTRATION OF BELEODAQ (1,000 MG/M²) AND WARFARIN (5 MG), A KNOWN CYP2C9 SUBSTRATE, DID NOT INCREASE THE AUC OR CMAX OF EITHER R-OR S-WARFARIN.
BELINOSTAT IS LIKELY A GLYCOPROTEIN (P-GP) SUBSTRATE BUT IS UNLIKELY TO INHIBIT P-GP.
PHARMACOGENOMICS
UGT1A1 ACTIVITY IS REDUCED IN INDIVIDUALS WITH GENETIC POLYMORPHISMS THAT LEAD TO REDUCED ENZYME ACTIVITY SUCH AS THE UGT1A1*28 POLYMORPHISM. APPROXIMATELY 20% OF THE BLACK POPULATION, 10% OF THE WHITE POPULATION, AND 2% OF THE ASIAN POPULATION ARE HOMOZYGOUS FOR THE UGT1A1*28 ALLELE. ADDITIONAL REDUCED FUNCTION ALLELES MAY BE MORE PREVALENT IN SPECIFIC POPULATIONS.
BECAUSE BELINOSTAT IS PRIMARILY (80 -90%) METABOLIZED BY UGT1A1, THE CLEARANCE OF BELINOSTAT COULD BE DECREASED IN PATIENTS WITH REDUCED UGT1A1 ACTIVITY (E.G., PATIENTS WITH UGT1A1*28 ALLELE). REDUCE THE STARTING DOSE OF BELEODAQ TO 750 MG/M² IN PATIENTS KNOWN TO BE HOMOZYGOUS FOR THE UGT1A1*28 ALLELE TO MINIMIZE DOSE LIMITING TOXICITIES.
CLINICAL STUDIES
RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA (PTCL)
IN AN OPEN-LABEL, SINGLE-ARM, NON-RANDOMIZED INTERNATIONAL TRIAL CONDUCTED AT 62 CENTERS, 129 PATIENTS WITH RELAPSED OR REFRACTORY PTCL WERE TREATED WITH BELEODAQ 1,000 MG/M² ADMINISTERED OVER 30 MINUTES VIA IV INFUSION ONCE DAILY ON DAYS 1-5 OF A 21-DAY CYCLE. THERE WERE 120 PATIENTS WHO HAD HISTOLOGICALLY CONFIRMED PTCL BY CENTRAL REVIEW EVALUABLE FOR EFFICACY. PATIENTS WERE TREATED WITH REPEAT CYCLES EVERY THREE WEEKS UNTIL DISEASE PROGRESSION OR UNACCEPTABLE TOXICITY.
THE PRIMARY EFFICACY ENDPOINT WAS RESPONSE RATE (COMPLETE RESPONSE AND PARTIAL RESPONSE) AS ASSESSED BY AN INDEPENDENT REVIEW COMMITTEE (IRC) USING THE INTERNATIONAL WORKSHOP CRITERIA (IWC) (CHESON 2007). THE KEY SECONDARY EFFICACY ENDPOINT WAS DURATION OF RESPONSE. RESPONSE ASSESSMENTS WERE EVALUATED EVERY 6 WEEKS FOR THE FIRST 12 MONTHS AND THEN EVERY 12 WEEKS UNTIL 2 YEARS FROM THE START OF STUDY TREATMENT. DURATION OF RESPONSE WAS MEASURED FROM THE FIRST DAY OF DOCUMENTED RESPONSE TO DISEASE PROGRESSION OR DEATH. RESPONSE AND PROGRESSION OF DISEASE WERE EVALUATED BY THE IRC USING THE IWC.
TABLE 3 SUMMARIZES THE BASELINE DEMOGRAPHIC AND DISEASE CHARACTERISTICS OF THE STUDY POPULATION, WHO WERE EVALUABLE FOR EFFICACY.
TABLE 3: BASELINE PATIENT CHARACTERISTICS (PTCL POPULATION)
CHARACTERISTICS EVALUABLE PATIENTS (N=120)
AGE (YEARS)
MEDIAN (RANGE) 64.0 (29-81)
SEX, %
MALE 52
FEMALE 48
RACE, %
WHITE 88
BLACK 6
ASIAN 3
LATIN 3
OTHER 2
PTCL SUBTYPE BASED ON CENTRAL DIAGNOSIS, %
PTCL UNSPECIFIED (NOS) 64
ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA (AITL) 18
ALK-1 NEGATIVE ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) 11
OTHER 7
BASELINE PLATELET COUNT, %
? 100,000/?L 83
< 100,000/?L 17
ECOG PERFORMANCE STATUS, %
0 34
1 43
2 22
3 1
MEDIAN TIME (MONTHS) FROM INITIAL PTCL DIAGNOSIS (RANGE) 12.0 (2.6 - 266.4)
MEDIAN NUMBER OF PRIOR SYSTEMIC THERAPIES (RANGE) 2.0 (1-8)
IN ALL EVALUABLE PATIENTS (N = 120) TREATED WITH BELEODAQ, THE OVERALL RESPONSE RATE PER CENTRAL REVIEW USING IWC WAS 25.8% (N = 31) (TABLE 4) WITH RATES OF 23.4% FOR PTCL, NOS AND 45.5% FOR AITL, THE TWO LARGEST SUBTYPES ENROLLED.
TABLE 4: RESPONSE ANALYSIS PER CENTRAL ASSESSMENT USING IWC IN PATIENTS WITH RELAPSED OR REFRACTORY PTCL
RESPONSE RATE EVALUABLE PATIENTS
(N=120)
N (%) (95% CI)
CR+PR 31 (25.8) 18.3-34.6
CR 13 (10.8) 5.9-17.8
PR 18 (15.0) 9.1 - 22.7
CI=CONFIDENCE INTERVAL, CR=COMPLETE RESPONSE, PR=PARTIAL RESPONSE
THE MEDIAN DURATION OF RESPONSE BASED ON THE FIRST DATE OF RESPONSE TO DISEASE PROGRESSION OR DEATH WAS 8.4 MONTHS (95% CI: 4.5 - 29.4). OF THE RESPONDERS, THE MEDIAN TIME TO RESPONSE WAS 5.6 WEEKS (RANGE 4.3 -50.4 WEEKS). NINE PATIENTS (7.5%) WERE ABLE TO PROCEED TO A STEM CELL TRANSPLANT AFTER TREATMENT WITH BELEODAQ.