qanastek/EMEA-V3 huggingface dataset:
In an interaction study based on data from 17 patients, assessing the effect of omeprazole, a potent CYP2C19 inhibitor, there was no significant effect on the pharmacokinetics of bortezomib.
Fi studju dwar interazzjoni bbażat fuq data minn 17 il- pazjent, fejn ġie studjat l- effett ta ’ omeprazole, inibitur potenti ta ’ CYP2C19, ma kienx hemm effett sinifikattiv fuq il- farmakokinetika ta ’ bortezomib.
Patients should be closely monitored when given bortezomib in combination with CYP2C19 inhibitors (e. g. fluoxetine).
Il- pazjenti għandhom jiġu monitorjati bir- reqqa meta jingħataw bortezomib flimkien ma ’ inibituri potenti CYP2C19 (ngħidu aħna fluoxetine).
In the absence of interaction studies investigating the effect of CYP3A4 inducers on the pharmacokinetics of bortezomib, patients should be closely monitored when given bortezomib in combination with potent CYP3A4 inducers (e. g. rifampicin).
Fl- assenza ta ’ studji dwar l- interazzjoni bejn prodotti farmaċewtiċi fejn ġie investigat l- effett ta ’ indutturi CYP3A4 fuq il- farmakokinetika ta ’ bortezomib, il- pazjenti għandhom jiġu monitorjati bir - reqqa meta jingħataw bortezomib flimkien ma ’ indutturi CYP3A4 (ngħidu aħna rifampicin).
An interaction study assessing the effect of melphalan-prednisone on bortezomib showed a 17% increase in mean bortezomib AUC based on data from 21 patients.
Studju dwar interazzjoni li jistma l- effett ta ’ melphalan- prednisone fuq bortezomib wera żieda ta ’ 17% fl- AUC medja ta ’ bortezomib ibbażat fuq dejta minn 21 pazjent.
This is not considered clinically relevant.
Dan m’ huwiex ikkunsidrat klinikament rilevanti.
During clinical trials, hypoglycemia and hyperglycemia were uncommonly and commonly reported in diabetic patients receiving oral hypoglycemics.
Waqt provi kliniċi, ġew rappurati ipogliċemja u ipergliċemja b’ mod komuni u mhux komuni f' pazjenti dijabetiċi li kienu qed jirċievu ipogliċemiċi orali.
Patients on oral antidiabetic agents receiving
Pazjenti li qed jieħdu sustanzi orali għal kontra d - dijabete u li qed jingħataw il- kura b' VELCADE għandhom bżonn monitoraġġ bir- reqqa tal- livell tal - glukosju fid- demm, u bdil fid- doża tal- mediċina għal kontra d- dijabete.
The teratogenic potential of bortezomib has not been fully investigated.
Il- potenzjal teratoġeniku ta 'bortezomib għadu ma ġiex studjat għal kollox.
In non-clinical studies, bortezomib had no effects on embryonal/ foetal development in rats and rabbits at the highest maternally tolerated doses.
Fi studji mhux kliniċi, bortezomib ma kellux effetti fuq l- iżvilupp tal- embriju/ fetu fil- firien u l- fniek bl- ogħla dożi li setgħu jiġu tollerati mill- ommijiet.
Animal studies to determine the effects of bortezomib on parturition and post-natal development were not conducted (see section 5.3).
Ma sarux studji fl- annimali dwar l- effetti ta ’ bortezomib fuq il- ħlas u l- iżvilupp wara l- ħlas (ara sezzjoni 5. 3).
VELCADE should not be used during pregnancy unless clearly necessary.
VELCADE m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
For VELCADE no clinical data with regard to exposure during pregnancy are available.
Għal VELCADE m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
Male and female patients of childbearing potential must use effective contraceptive measures during and for 3 months following treatment.
Pazjenti rġiel u nisa li jista ’ jkollhom it- tfal għandhom jużaw metodi effettivi ta 'kontraċezzjoni waqt il- kura u sa tliet xhur wara l - kura.
If VELCADE is used during pregnancy, or if the patient becomes pregnant while receiving this medicinal product, the patient should be informed of potential for hazard to the foetus.
Jekk VELCADE jintuża waqt it- tqala, jew jekk il- pazjenta toħroġ tqila meta tkun qed tingħata l - prodott mediċinali, il- pazjenta għandha tiġi infurmata dwar il- potenzjal ta 'ħsara għall- fetu.
It is not known whether bortezomib is excreted in human milk.
Mhux nagħruf jekk bortezomib joħroġx mal- ħalib tas- sider.
Because of the potential for serious undesirable effects in breast-fed infants, lactation should be discontinued during treatment with VELCADE.
Minħabba l- potenzjal ta 'effetti serji mhux mixtieqa fit- trabi li jitreddgħu, it- treddigħ għandu jitwaqqaf waqt kura b’ VELCADE.
VELCADE may have a moderate influence on the ability to drive and use machines.
VELCADE għandu effett moderat fuq il- ħila ta 'sewqan u l- użu ta ’ magni.
VELCADE may be associated with fatigue very commonly, dizziness commonly, syncope uncommonly, orthostatic/ postural hypotension or blurred vision commonly.
VELCADE jista 'jkollu x' jaqsam b’ mod komuni ħafna ma' għeja, b’ mod komuni ma ’ sturdament, b’ mod mhux komuni ma ’ telf mis- sensi, b’ mod komuni ma ’ ipotensjoni ortostatika/ tal- qagħda jew vista mċajpra.
Therefore, patients must be cautious when operating machinery, or when driving (see section 4.8).
Għalhekk, il - pazjenti għandhom joqogħdu attenti meta jħaddmu l- magni jew meta jsuqu (ara sezzjoni 4. 8).
The following undesirable effects were considered by the investigators to have at least a possible or probable causal relationship to VELCADE during the conduct of 5 non-comparative Phase II studies and 1 comparative Phase III trial VELCADE vs. dexamethasone in 663 patients with relapsed or refractory multiple myeloma, of whom 331 received VELCADE as single agent.
Il- bażidata dwar sigurtà tinkludi
The safety database comprises data from patients with multiple myeloma or B-cell lymphocytic leukemia (CLL).
8 tagħrif mill- pazjenti b’ majloma multipla jew lewċemija limfoċitika taċ- ċelluli- B (CLL).
Patients were treated with VELCADE as a single agent, or in combination with dexamethasone.
Il- pazjenti kienu kkurati b’ VELCADE waħdu, jew flimkien ma ’ dexamethasone.
Adverse reactions are listed below by system organ class and frequency grouping.
Ir- reazzjonijiet avversi huma mniżżla hawn taħt skond il- kategorija tas- sistema ta 'l- organi u l- grupp ta ’ frekwenza.
Frequencies are defined as:
Il- frekwenzi huma definiti b' dan il- mod:
Very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Komuni ħafna (≥1/ 10); komuni (≥1/ 100 sa < 1/ 10); mhux komuni (≥1/ 1, 000 sa < 1/ 100); rari (≥1/ 10, 000 sa < 1/ 1, 000); rari ħafna (< 1/ 10, 000), mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
L- effetti mhux mixtieqa huma mniżżla skond is- serjetà tagħhom bl - aktar serji jitniżżlu l- ewwel Tabella 4:
Adverse reactions in patients with relapsed/ refractory multiple myeloma Infections and infestations Very common: herpes zoster (including disseminated).
Reazzjonijiet avversi f’ pazjenti b’ majloma multipla b’ episodju ġdid/ refrattorja għall- kura Infezzjonijiet u infestazzjonijiet Komuni ħafna: herpes zoster (inkluż dak disseminat).
Uncommon: sepsis, bacteraemia, pneumonia pneumococcal, bronchopneumonia, upper and lower respiratory tract infection, catheter related infection, pleural infection, haemophilus infection, cytomegalovirus infection, influenza, infectious mononucleosis, varicella, urinary tract infection, gastroenteritis, candidal infection, fungal infection, post herpetic neuralgia, oral candidiasis, blepharitis, infection.
Komuni: pulmonite, bronkite, sinużite, nasofarinġite, herpes simplex Mhux komuni: sepsis, batteremija, pulmonite pnewmokokkali, bronkopulmonite, infezzjoni fil- parti ta 'fuq u ta ’ isfel tas- sistema respiratorja, infezzjoni marbuta mal- kateter, infezzjoni plewrali, infezzjoni emofilika, infezzjoni tal- sajtomegalovirus, influwenza, mononukleużi infettiva, variċella, infezzjoni ta ’ l- apparat urinali, gastroenterite, infezzjoni kandidali, infezzjoni fungali, newralġja post - erpetika, kandidaisi orali, blefarite, infezzjoni.
Neoplasms benign and malignant (including cysts and polyps) Uncommon: tumour lysis syndrome (see section 4.4).
Neoplażmi beninni u malinni (inkluż ċesti u polipi) Mhux komuni: sindromu tal- lysis tat- tumur (ara sezzjoni 4. 4).
Blood and the lymphatic system disorders (see section 4.4) Very common:
Disturbi tad- demm u tas- sistema limfatika (ara sezzjoni 4. 4) Komuni ħafna: tromboċitopenja, newtropinja, anemija.
thrombocytopenia, neutropenia, anaemia.
Disturbi fis- sistema immuni Mhux komuni:
Uncommon: pancytopenia, febrile neutropenia, haemolytic anaemia, thrombocytopenic purpura, lymphadenopathy.
ipersensittività, ipersensittività medjata mill- immunocomplex, reazzjonijiet li
Immune system disorders Uncommon: hypersensitivity, immunocomplex mediated hypersensitivity, potentially immunocomplex-mediated reactions, such as serum-sickness-type reaction, polyarthritis with rash and proliferative glomerulonephritis (see section 4.4).
potenzjalment huma marbuta ma ’ l- immunokompless, bħal’ mhi reazzjoni tat- tip tal- marda tas- serum, polijartrite b’ raxx u glomerulonefrite proliferattiva (ara sezzjoni 4. 4)
Endocrine disorders Uncommon: inappropriate antidiuretic hormone (ADH) secretion.
Disturbi fis- sistema endokrinarja Mhux komuni: sekrezzjoni ta ’ l- ormon antidijuretiku (ADH) mhux f’ waqtha.
Metabolism and nutrition disorders Very common:
Distrubi tal- metaboliżmu u n- nutrizzjoni Komuni ħafna: tnaqqis ta 'l- aptit Komuni:
appetite decreased.
Mhux komuni:
Common: dehydration, hypokalaemia, hyperglycaemia.
diżidratazzjoni, ipokalimja, ipergliċemja iperkalemija, kakeksja, iperkalċimja, ipokalċimja, ipernatremija, iponatremija,
Uncommon: hyperkalaemia, cachexia, hypercalcaemia, hypocalcaemia, hypernatraemia, hyponatraemia, hypoglycaemia, hyperuricaemia, vitamin B12 deficiency, appetite increased, hypomagnesaemia, hypophosphataemia.
ipogliċemija, iperuriċemija, żieda fl- aptit minħabba nuqqas tal- vitamina B12, ipomagnesemija, ipofosfatemija.
Psychiatric disorders Common: confusion, depression, insomnia, anxiety.
konfużjoni, depressjoni, insomnja, ansjetà.
Uncommon: agitation, delirium, hallucinations, restlessness, mood swings, mental status changes, sleep disorder, irritability, abnormal dreams.
Uncommon: aġitazzjoni, delirju, alliċunazzjonijiet, nuqqas ta 'kwiet, bdil fil- burdata, bdil fl- istat mentali, disturbi fl- irqad, irritabilità, ħolm mhux normali.
Nervous system disorders (see sections 4.4 and 4.7) Very common:
Disturbi fis- sistema nervuża (ara sezzjonijiet 4. 4 u 4. 7) Komuni ħafna: uġigħ ta 'ras.
peripheral neuropathy, peripheral sensory neuropathy (see section 4.4),
newropatija periferali, newropatija sensorja periferali, (ara sezzjoni 4. 4), paresteżja,
paraesthesia, headache.
disasteżja, ipoasteżja, tferfir.
Common: polyneuropathy, peripheral neuropathy aggravated, dizziness (excluding vertigo), dysgeusia, dysaesthesia, hypoaesthesia, tremor.
(ara sezzjoni 4. 4), newropatija motorja periferali, sinkope, peresisi, telf ta 'l- attenzjoni, żieda fl- attività,
Uncommon: paraplegia, intracranial haemorrhage, subarachnoid haemorrhage convulsions (see section 4.4), peripheral motor neuropathy, syncope, paresis, disturbance in attention, increased activity, ageusia, somnolence, migraine, cognitive disorder, jerky movements, dizziness postural, sciatica, mononeuropathy, speech disorder, restless leg syndrome.
9 agewsija, tħeddil, emikranja, disturbi konjittivi, muvimenti f’ daqqa, sturdament tal- qagħda, xjatika, mononewropatija, disturbi fit- taħdit, sindromu taċ- ċaqlieq tar- riġel.
Eye disorders Common: vision blurred (see section 4.7), eye pain.
Mhux komuni:
Uncommon: eye haemorrhage, vision abnormal, dry eye, conjunctivitis, eye discharge, photophobia, eye irritation, lacrimation increased, conjunctival hyperaemia, eye swelling.
vista mċajpra (ara sezzjoni 4. 7) uġiegħ fl- għajnejn. fsada fl- għajnejn, vista mhux normali, għajnejn niexfa, konġunktivite, għajnejn
9 Ear and labyrinth disorders Common: vertigo.
vertigo
Uncommon: deafness, tinnitus, hypoacusis, hearing impaired.
Mhux komuni: truxija, tinnitus, ipoakużi, indeboliment fis- smiegħ
Cardiac disorders Uncommon: cardiac arrest, cardiogenic shock, myocardial infarction, angina pectoris, angina unstable, development or exacerbation of congestive heart failure (see section 4.4), cardiac failure, ventricular hypokinesia, pulmonary oedema and acute pulmonary oedema, sinus arrest, atrioventricular block complete, tachycardia, sinus tachycardia, supraventricular tachycardia, arrhythmia, atrial fibrillation, palpitations.
instabbli, żvilupp jew tħarrix ta ’ insuffiċjenza konġestiva tal- qalb (ara sezzjoni 4. 4), insuffiċjenza kardijaka, ipokinesja ventrikolari, edema pulmonarja, edema pulmonarja akuta, attakk tas- sinus, imblokk sħiħ atrijoventrikulari, takikardja, takikardja tas- sinus, arritmja, taħbit mgħaġġel tal- qalb, palpitazzjonijiet.
Rare: new onset of decreased left ventricular ejection fraction.
Rari: insuffiċjenza mill- ġdid tat- tfigħ ‘ il barra ventrikolari tax- xellug
Vascular disorders Common: hypotension, orthostatic and postural hypotension (see sections 4.4 and 4.7), phlebitis, haematoma, hypertension.
ipotensjoni, ipotensjoni ortostatika u tal- qagħda (ara sezzjonijiet 4. 4 u 4. 7), flebite, ematoma, ipertensjoni.
Uncommon: cerebral hemorrhage, vasculitis, cerebrovascular accident, pulmonary hypertension, petechiae, ecchymosis, purpura, vein discolouration, vein distended, wound hemorrhage, flushing, hot flushes.
fsada ċelebrali, vaskulite, inċident ċelebrovaskulari, ipertensjoni pulmonari,
Respiratory, thoracic and mediastinal disorders Very common:
petechiae, ekkimożi, purpura, bidla fil- kulur tal- vini, vini minfuħa, fsad tal- ferita, ħmura fil- wiċċ, fawra fil- wiċċ.
dyspnoea.
Mhux komuni:
Common: dyspnoea exertional, epistaxis, cough, rhinorrhoea.
dispnea bl- isforz, epistażi, sogħla, rinorrea. waqfien respiratorju, ipoksja, konġestjoni pulmonarja, effużjoni plewrali, ażma,
Uncommon: respiratory arrest, hypoxia, pulmonary congestion, pleural effusion, asthma, respiratory alkalosis, tachypnoea, wheezing, nasal congestion, hoarseness, rhinitis, hyperventilation, orthopnoea, chest wall pain, sinus pain, throat tightness, productive cough.
alkalożi respiratorja, takipnea, tħarħir, imnieħer miżdud, ħanqa, rinite, iperventilazzjoni, ortopnea, uġiegħ mal- ġenb tas- sider, uġiegħ tas- sinus, gerżuma magħfusa, tqaħqiħa produttiva.
Gastrointestinal disorders (see section 4.4) Very common:
Kumuni:
vomiting, diarrhoea, nausea, constipation.
uġigħ addominali, stomatite, dispepsja, ippurgar maħlul, uġigħ fil- parti ta’ fuq iż- żaqq,
Common: abdominal pain, stomatitis, dyspepsia, loose stools, abdominal pain upper, flatulence, abdominal distension, hiccups, mouth ulceration, pharyngolaryngeal pain, dry mouth.
Mhux komuni:
Uncommon: acute pancreatitis, ileus paralytic, antibiotic associated colitis, colitis, haematemesis, diarrhoea haemorrhagic, gastrointestinal haemorrhage, rectal haemorrhage, enteritis, dysphagia, abdominal discomfort, eructation, gastrointestinal motility disorder, oral pain, retching, change in bowel habit, spleen pain, oesophagitis, gastritis, gastro-oesophageal reflux disease, gastrointestinal pain, gingival bleeding, gingival pain, hiatus hernia, irritable bowel syndrome, oral mucosal petechiae, salivary hypersecretion, tongue coated, tongue discolouration, faecal impaction.
kolite, ematemite, dearreja emorraġika, fsada gastrointestinali, fsada rettali, enterite, disfaġja, skumdità fiż- żaqq, tifwiq, disturb fil- moviment gastro- intestinali, uġigħ fil- ħalq, tqalligħ, bidla fid - drawwa ta 'l- ippurgar, uġigħ fil- milsa, oseofaġite, gastrite, disturbi tar- rifluss gastro- esofaġali, uġigħ gastrointestinali, fsad ġenġivali, uġigħ ġenġivali, ernja hiatus, sindromu tal- musrana irritabbli, petejki mukożali orali, ipersekrezzjoni tas- saliva, ilsien miksi, bidla fil- kulur ta ’ l- ilsien, ippurgar kompattat.
Hepato-biliary disorders (see section 4.4) Uncommon: hepatitis, hepatic haemorrhage, hypoproteinaemia, hyperbilirubinaemia.
Disturbi fil- fwied u fil- marrara (ara sezzjoni 4. 4) Mhux komuni: epatite, fsada epatika, ipoprotenimija, iperbilirubimija.
Skin and subcutaneous tissue disorders Very common:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni ħafna: raxx.
Common: periorbital skin, eczema.
edema periorbitali, urtikarja, raxx bil- ħakk, ħakk, eritema, żieda fl- għaraq,, ġilda niexfa,
rash. oedema, urticaria, rash pruritic, pruritus, erythema, sweating increased, dry
raxx vaskulitiku, raxx eritematoniku, reazzjoni fotosensittiva, tbenġila, raxx
Uncommon: vasculitic rash, rash erythematous, photosensitivity reaction, contusion, pruritus generalised, rash macular, rash papular, psoriasis, rash generalized, eyelid oedema, face oedema, dermatitis, alopecia, nail disorder, skin discolouration, dermatitis atopic, hair texture abnormal, heat rash, night sweats, pressure sore, ichthyosis, skin nodule.
ġeneralizzat, raxx makulari, raxx papulari, psorijażi, raxx ġeneralizzat, edema tal- kappell ta ’ l- għajn, edema tal- wiċċ, dermatite, waqgħa tax- xahar, mard tad- dwiefer, bidla fil- kulur tal- ġilda, dermatite
Musculoskeletal, connective tissue and bone disorders Very common:
10 atopika, għamla tax- xahar mhux normali, raxx tas- sħana, għaraq bil- lejl, ferita tas- sodda, iktjosi, għoqda fil- ġilda.
myalgia.
Komuni:
Common: muscle weakness, musculoskeletal pain, pain in limb, muscle cramps, arthralgia, bone pain, back pain, peripheral swelling.
telqa tal- muskoli, uġigħ muskoloskeletali, uġigħ fid- driegħ jew ir- riġel, bugħawwieġ,
Uncommon: muscle spasms, muscle twitching or sensation of heaviness, muscle stiffness, joint swelling, joint stiffness, buttock pain, swelling, pain in jaw.
spażmi fil- muskoli, tferfir tal- muskoli jew sensazzjoni ta 'toqol, ebusija tal - uġigħ fil- muskolu tal- warrani, nefħa, uġigħ fix- xedaq.
10 Renal and urinary disorders Common: renal impairment, dysuria.
Mhux komuni:
Uncommon: renal failure acute, renal failure, oliguria, renal colic, haematuria, proteinuria, urinary retention, urinary frequency, difficulty in micturition, loin pain, urinary incontinence, micturition urgency.
proteinurja, iżżomm lura milli tagħmel l- urina, tagħmel l- urina b' mod frekwenti, diffikulta` biex tagħmel l- urina, uġigħ fil- ġenbejn, inkontinenza fl- urina, urgenza biex tagħmel l- urina.
Reproductive system and breast disorders Uncommon: testicular pain, erectile dysfunction.
Disturbi fis- sistema riproduttiva u fis- sider Mhux komuni: uġigħ testikulari u disfunzjoni erettili.
General disorders and administration site conditions Very common:
Komuni:
fatigue (see section 4.7), pyrexia.
Mhux komuni:
Common: asthenia, weakness, lethargy, rigors, malaise, influenza like illness, oedema peripheral, chest pain, pain, oedema.
taqa ’, fsada tal- mukożi, infjammazzjoni tal- mukożi, newralġja, flebite tas- sit ta 'l -
Uncommon: fall, mucosal haemorrhage, mucosal inflammation, neuralgia, injection site phlebitis, extravasation inflammation tenderness, injection site erythema, feeling cold, chest pressure sensation, chest discomfort, groin pain, chest tightness.
injezzjoni, sensittività minn infjammazzjoni minn ekstravażazzjoni, eritema tas- sit ta ’ l- injezzjoni, tħoss il- bard, sensazzjoni ta ’ pressjoni fuq is- sider, skumdità fis- sider, uġigħ fil- ġenbejn, għafsa fis - sider.
Investigations Common: weight decreased, blood lactate dehydrogenase increased.
żieda fil- piż, żieda fid- dehydrogenase tal- lactate tad- demm żieda fl- alanine aminotransferase, żieda fl- aspartate aminotransferase, żieda fil - żieda fil- phosphatase ta 'l- alkalina tad- demm, żieda fil- kreatitina tad- demm,
Uncommon: alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, blood alkaline phosphatase increased, blood creatinine increased, blood urea increased, gamma-glutamyltransferase increased, blood amylase increased, liver function tests abnormal, red blood cell count decreased, white blood cell count decreased, blood bicarbonate decreased, heart rate irregular, C-reactive protein increased, blood phosphate decreased, weight increased.
żieda tad- demm fl- urea, żieda fil- gamma- glutamyltransferase, żieda fl- amylase tad- demm, testijiet tal - funzjoni tal- fwied mhux normali, tnaqqis fl- għadd taċ- ċelluli ħomor tad- demm, tnaqqis fl- għadd taċ - ċelluli bojod tad- demm, żieda fil- bikarbonat tad- demm, tħabbit tal- qalb irregolari, żieda fil- proteina C - reattiva, żieda fil- fosfat tad- demm, żieda fil- piż.
Injury and poisoning Uncommon: catheter related complications, post procedural pain, post procedural haemorrhage, burns.
komplikazzjonijiet marbuta mal- kateter, uġigħ ta ’ wara l- proċedura, fsad ta ’ wara l -
Summary of safety data in patients with previously untreated multiple myeloma:
Sommarju ta ’ tagħrif ta ’ sigurtà f’ pazjenti b’ majloma multipla li qatt ma kienet ikkurata qabel:
The following table 5 describes safety data from 340 patients with previously untreated multiple myeloma who received VELCADE (1.3 mg/ m2) in combination with melphalan (9 mg/ m2) and prednisone (60 mg/ m2) in a prospective Phase III study.
It- tabella 5 li ġejja tiddeskrivi d- dejta ta ’ sigurtà minn 340 pazjent b’ majloma multipla li qatt ma kienet ikkurata qabel li rċievew VELCADE (1. 3 mg/ m2) flimkien ma ’ melphalan (9 mg/ m2) u prednisone (60 mg/ m2) fi studju prospettiv tal- Fażi III.
Overall, the safety profile of patients treated with VELCADE in monotherapy was similar to that observed in patients treated with VELCADE in combination with melphalan and prednisone.
Ġeneralment, il- profil ta ’ sigurtà tal- pazjenti kkurati b’ VELCADE f’ monoterapija kien jixbah lil dak osservat f’ pazjenti kkurati b’ VELCADE flimkien ma ’ melpalan u prednisone.
Table 5:
11 Tabella 5:
Treatment emergent drug-related adverse reactions reported in ≥ 10% of patients treated with VELCADE in combination with melphalan and prednisone -------------- Vc+M+P ------------ ---------------- M+P ---------------
Reazzjonijiet avversi relatati mal- mediċina li tfaċċaw mal- kura rrappurtati f’ ≥ 10% tal - pazjenti kkurati b’ VELCADE flimkien ma ’ melphalan u prednisone -------------- Vc+M+P -------------- ---------------- M+P ---------------
(%) Total Toxicity Grade, n (%)
Total Grad ta ’ tossiċità, n (%) Total Grad ta ’ tossiċità, n (%) Klassifikazzjoni tas- Sistema ta ’ l - Organi MedDRA Terminu Ppreferut Infezzjonijiet u infestazzjonijiet
Herpes Zoster Blood and lymphatic system disorders
Herpes Zoster Disturbi tad- demm u tas- sistema limfatika
Thrombocytopenia Neutropenia Anaemia Leukopenia Lymphopenia Metabolism and nutrition disorders
Tromboċitopenja Newtropenja Anemija Lewkopenja Limfopenja Disturbi fil- metaboliżmu u n - nutrizzjoni
164 (48) 60 (18) 160 (47) 101 (30) 33 109 (32) 41 (12) 108 (32) 64 (19) 78 (23) 46 (14)
164 (48) 60 (18) 160 (47) 101 (30) 33 109 (32) 41 (12) 108 (32) 64 (19) 78 (23) 46 (14)
57 (17) 140 (42) 48 (14) (10) 143 (42) 77 (23) 4 (1) 156 (46) 61 (18) 8 (2) 93 (28) 53 (16) 17 (5) 51 (15) 26 (8)
57 (17) 140 (42) 48 (14) (10) 143 (42) 77 (23) 4 (1) 156 (46) 61 (18) 8 (2) 93 (28) 53 (16) 17 (5) 51 (15) 26 (8)
Anorexia Psychiatric disorders
Anoreksja Disturbi psikjatriċi
Insomnia Nervous system disorders
Insomnja Disturbi fis- sistema nervuża
Peripheral Neuropathy
Newropatija periferali
156 (46)
156 (46) 42 (12)
Neuralgia Paraesthesia Gastrointestinal disorders
Nevralġija Paresteżija Disturbi gastro- intestinali
117 (34) 42 (12)
117 (34) 27 (8) 42 (12) 6 (2)
134 (39)
134 (39) 1
119 (35)
119 (35) 19 (6)
Vomiting Constipation Abdominal Pain Upper Skin and subcutaneous tissue disorders
Rimettar Stitikezza
87 (26) 77 (23) 34 (10)
87 (26) 77 (23)
13 (4) 2 (1) 1 (< 1)
13 (4) 2 (1)
41 (12) 14 (4) 20 (6)
41 (12) 14 (4)
2 (1) 0 0
0 0
Rash General disorders and administration site conditions
Raxx Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata
Fatigue Asthenia
Għeja kbira Astenja
In the Phase III study in patients with previously untreated multiple myeloma, 27% of patients received prophylactic antivirals in the Vc+M+P arm.
Riattivazzjoni tal- virus ta ’ l- Erpete zoster Fl- istudju tal- Fażi III f’ pazjenti b’ majloma multipla li qatt ma kienet ikkurata qabel, 27% tal- pazjenti rċievew mediċini kontra l- virus bħala profilassi fil- fergħa Vc+M+P.
In this study, herpes zoster reactivation was more common in patients treated with Vc+M+P compared with M+P (11% vs 3% respectively).
F’ dan l- istudju, riattivazzjoni tal - virus erpete zoster kienet aktar komuni f’ pazjenti kkurati b’ Vc+M+P meta mqabbel ma ’ M+P (11% vs 3% rispettivament).
Three (3%) of the 91 patients in the Vc+M+P treatment group who received prophylactic antivirals developed herpes zoster reactivation.
Tlieta (3%) mill- 91 pazjent fil- grupp ta ’ kura b’ Vc+M+P li rċievew mediċini kontra l- virus bħala profilassi żviluppaw riattivazzjoni ta ’ l- erpete zoster.
Post-marketing experience Clinically significant adverse reactions are listed in Table 6, if they have been reported during post approval use of VELCADE and may or may not have been reported in clinical trials.
Esperjenza ta ’ wara t- tqegħid tal- prodott fis- suq F’ Tabella 6 jitniżżlu reazzjonijiet mhux mixtieqa li huma klinikament sinifikanti jekk ġew irrapurtati waqt l- użu wara l- approvazzjoni ta ’ VELCADE u setgħu ġew jew ma ġewx irrapurati fi provi kliniċi.
Their frequency is not known.
Il- frekwenza tagħhom mhix magħrufa.
Table 6:
12 Tabella 6:
Adverse reactions from post-marketing reports Infections and infestations Not known:
Reazzjonijiet avversi mir- rapporti ta ’ wara t- tqegħid fis- suq Infezzjonijiet u infestazzjonijiet Herpes meningoencephalitis, xokk settiku Mhux magħruf:
Immune system disorders
Disturbi fis- sistema immuni Angjoedima Mhux magħruf:
Nervous system disorders
Disturbi fis- sistema nervuża Mhux magħruf:
Not known:
Disturbi fll- għajnejn Mhux magħruf:
Eye disorders
Disturbi fil- qalb
Encephalopathy, autonomic neuropathy
Enċefalopatija, newropatija awtonomika Herpes fl- għajnejn
Gastrointestinal disorders
Imblukkar kardijaku, perikardite, waqfien kardijaku jew kardjopulmonari, arritmiji ventrikulari, imblukkkar totali atriju - Mhux magħruf: ventrikulari, fibrillazzjoni atrijali, takikardija, takikardija tas- sinus u ventrikulari.
disease, pulmonary hypertension, respiratory failure, pulmonary alveolar haemorrhage, acute pulmonary oedema, pulmonary oedema, pulmonary embolism, peripheral embolism
Disturbi respiratorji, toraċiċi u medjastinali (ara sezzjoni 4, 4) Pnewmonite, pnewmonja, pulmonite interstitjali, Sindrome ta ’ Għeja Respiratorja Akuta (ARDS), mard pulmonari akut imxerred infiltrattiv, pressjoni pulmonari għolja, insuffiċjenza respiratorja, Mhux magħruf: emorraġija alveolari pulmonari, edima pulmonari akuta edima pulmonari, emboliżmu pulmonari, emboliżmu periferali Disturbi gastro- intestinali Mhux magħruf:
Ischemic colitis
Kolite iskemika
Liver failure
Insuffiċjenza tal- fwied
(For preclinical cardiovascular safety pharmacology studies, see section 5.3.
Fil- pazjenti, doża eċċessiva iktar minn darbtejn mid- doża rakkomandata ġiet marbuta ma ’ episodju akut ta ’ ipotensjoni sintomatika u trombositapenija b’ riżultati fatali (Għal studji prekliniċi kardjovaskulari ta ’ sigurtà farmakoloġika, ara sezzjoni 5. 3).
There is no known specific antidote for bortezomib overdose.
M’ hemmx antidotu speċifiku għal doża eċċessiva ta ’ bortezomib.
In the event of an overdose, the patient ’ s vital signs should be monitored and appropriate supportive care given to maintain blood pressure (such as fluids, pressors, and/ or inotropic agents) and body temperature (see sections 4.2 and 4.4).
Jekk tittieħed doża eċċessiva, is - sinjali vitali tal- pazjent għandhom ikunu monitorjati u għandha tingħata l- kura xierqa biex tinżamm il - pressjoni tad- demm (bħal fluwidi, pressors u/ jew aġenti inotropiċi) u t- temperatura tal- ġisem (ara sezzjonijiet 4. 2 u 4. 4).
Other antineoplastic agents, ATC code:
Sustanzi antineoplastiċi oħra, Kodiċi ATC:
This medicinal product has been authorised under “ Exceptional Circumstances”.
Dan il- prodott mediċinali ġie awtorizzat taħt ‘ Ċirkustanzi ta ’ Eċċezzjoni ’.
This means that for scientific reasons it has not been possible to obtain complete information on this medicinal product.
Dan ifisser li għal raġunijiet xjentifiċi ma kienx possibbli li tinkiseb informazzjoni kompleta dwar dan il- prodott mediċinali.
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
L - Aġenzija Ewropea dwar il- Mediċini (EMEA) ser tirrevedi kull tip ta ’ informazzjoni ġdida li toħroġ kull sena u ser taġġorna dan is- Sommarju tal- Karatteristiċi tal- Prodott, skond il- bżonn.
Mechanism of action Bortezomib is a proteasome inhibitor.
13 Mekkaniżmu kif jaħdem Bortezomib huwa inibitur tal- proteasome.
It is specifically designed to inhibit the chymotrypsin-like activity of the 26S proteasome in mammalian cells.
Huwa msawwar apposta biex jinibixxi l- attività li tixbaħ dik ta ’ chymotrypsin minn 26S proteasome f' ċelluli mammali.
The 26S proteasome is a large protein complex that degrades ubiquitinated proteins.
26S proteasome hija proteina komposta kbira li tiddegrada proteini ubikwitinati.
The ubiquitin-proteasome pathway plays an essential role in regulating the turnover of specific proteins, thereby maintaining homeostasis within cells.
Il- passaġġ proteasome ubikwitinat għandu sehem essenzjali biex jirregola l- ipproċessar ta 'proteini speċifiċi, u b' dan il- mod jinżamm l- omeostażi fiċ- ċelluli.
Inhibition of the 26S proteasome prevents this targeted proteolysis and affects multiple signalling cascades within the cell, ultimately resulting in cancer cell death.
L - inibizzjoni tal- 26S proteasome iżomm milli sseħħ din il- proteoliżi u taffettwa l- kaskati ta 'senjalazzjonijiet multipli fiċ- ċellula, li fl- aħħar mill- aħħar iwassal għall- mewt taċ- ċellula tal- kanċer.
Bortezomib is highly selective for the proteasome.
Bortezomib huwa selettiv ħafna għall- proteasome.
At 10 μ M concentrations, bortezomib does not inhibit any of a wide variety of receptors and proteases screened and is more than 1500-fold more selective for the proteasome than for its next preferable enzyme.
F' konċentrazzjonijiet ta '10 μM, bortezomib ma jinibixxi l- ebda wieħed minn varjeta' wiesgħa ta 'reċetturi u proteasi ttestjati u huwa iktar minn 1500 darba iktar selettiv għall- proteasome milli għall- enżima li jkun imiss.
The kinetics of proteasome inhibition were evaluated in vitro, and bortezomib was shown to dissociate from the proteasome with a t½ of 20 minutes, thus demonstrating that proteasome inhibition by bortezomib is reversible.
Il- kinetiċi ta 'l- inibizzjoni tal - proteasome ġew evalwati in vitro, u bortezomib intwera li jiddissoċja mill- proteasome b' t½ ta' 20 minuta, u b' hekk wera li l- inibizzjoni tal- proteasome minn bortezomib hija reversibbli.
Bortezomib mediated proteasome inhibition affects cancer cells in a number of ways, including, but not limited to, altering regulatory proteins, which control cell cycle progression and nuclear factor kappa B (NF-kB) activation.
L- inibizzjoni tal- proteasome permezz ta 'bortezomib jaffettwa ċ- ċelluli tal- kanċer b’ diversi modi, inkluż, imma mhux limitat, għall- bdil tal- proteini regolatorji, li jikkontrollaw iċ- ċiklu tal- progressjoni taċ- ċellula u l- attivazzjoni tal- fattur nukleari kappa B (NF- kB).
NF-kB is a transcription factor whose activation is required for many aspects of tumourigenesis,
L- inibizzjoni tal- proteasome iwassal għall- waqfien taċ- ċiklu taċ- ċellula u għall- apoptożi.
13 including cell growth and survival, angiogenesis, cell-cell interactions, and metastasis.
NF- kB huwa fattur ta 'traskrizzjoni li l - attivazzjoni tiegħu hemm bżonnha għal ħafna aspetti tal- ġenesi tat- tumur, inkluż l- iżvilupp u l - għajxien taċ- ċellula, l- anġjoġenesi, interazzjonijiet bejn iċ- ċelluli u l- metastażi.
In myeloma, bortezomib affects the ability of myeloma cells to interact with the bone marrow microenvironment.
Fil- majloma, bortezomib jaffettwa l- ħila taċ- ċelluli tal- majloma li jinteraġixxu mal- mikroambjent tal- mudullun.
Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types and that cancer cells are more sensitive to the pro-apoptotic effects of proteasome inhibition than normal cells.
Esperimenti wrew li bortezomib huwa ċitotossiku għal varjetà ta 'tipi ta' ċelluli tal- kanċer, u li ċ- ċelluli tal- kanċer huma iktar sentittivi għall- effetti preventivi ta 'l- inibizzjoni ta ’ proteasome milli ċelluli normali.
Bortezomib causes reduction of tumour growth in vivo in many preclinical tumour models, including multiple myeloma.
Bortezomib inaqqas it- tkabbir tat- tumur in vivo f' ħafna mudelli tumorali prekliniċi, inkluż il - majloma multipla.
Clinical efficacy in previously untreated multiple myeloma A prospective Phase III, international, randomised (1:1), open-label clinical study (VISTA) of 682 patients was conducted to determine whether VELCADE (1.3 mg/ m2) in combination with melphalan (9 mg/ m2) and prednisone (60 mg/ m2) resulted in improvement in time to progression (TTP) when compared to melphalan (9 mg/ m2) and prednisone (60 mg/ m2) in patients with previously untreated multiple myeloma.
Effikaċja klinika f’ majloma multipla li qatt ma kienet ikkurata qabel Studju kliniku prospettiv tal- Fazi III randomised (1: 1), open- label, internazzjonali (VISTA) ta ’ 682 pazjent kien magħmul biex jiġi dderminat jekk VELCADE (1. 3 mg/ m2) flimkien ma ’ melphalan (9 mg/ m2) u prednisone (60 mg/ m2) jirriżultawx f’ titjib fiż- żmien ta ’ progressjoni (TTP) meta mqabbel ma ’ melphalan (9 mg/ m2) u prednisone (60 mg/ m2) f’ pazjenti b’ majloma multipla li qatt ma kienet ikkurata qabel.
Treatment was administered for a maximum of 9 cycles (approximately 54 weeks) and was discontinued early for disease progression or unacceptable toxicity.
Il- kura kienet mogħtija għal massimu ta ’ 9 ċikli (bejn wieħed u ieħor 54 ġimgħa) u twaqqfet qabel fejn kien hemm progressjoni tal- marda jew tossiċità mhux aċċetabbli.
Baseline demographics and patient characteristics are summarized in Table 7.
Demografiċi tal - linja bażi u karatteristiċi tal- pazjent huma miġbura fil- qosor f’ Tabella 7.
Summary of baseline patient and disease characteristics in the VISTA study
Sommarju tal- karatteristiċi tal- pazjent u l- marda fil- linja bażi fl- istudju VISTA
Patient characteristics
Karatteristiċi tal- pazjent
Median age in years (range) Gender: male/ female
Età medja fi snin (medda) Sess: raġel/ mara
71.0 (57, 90) 51% / 49%
71. 0 (57, 90) 51% / 49%
71.0 (48, 91) 49% / 51%
71. 0 (48, 91) 49% / 51%
Race: caucasian/ asian/ black/ other Karnofsky performance status score ≤ 70 Hemoglobin < 100 g/ l Platelet count < 75 x 109/ l Disease Characteristics
Razza: kawkasu/ a/ asjatiku/ a/ iswed/ sewda/ oħra Punteġġ tal- performance status Karnofsky ≤70 Emoglobina < 100 g/ l Għadd tal- plejtlits < 75 x 109/ l Karatteristiċi tal- marda
Type of myeloma (%):
Tip ta ’ majloma (%):
IgG/ IgA/ Light chain Median β 2-microglobulin (mg/ l) Median albumin (g/ l) Creatinine clearance ≤ 30 ml/ min [n (%)]
Tneħħija tal- kreatinina ≤30 mL/ min [n (%)]
At the time of a pre-specified interim analysis, the primary endpoint, time to progression, was met and patients in the M+P arm were offered Vc+M+P treatment.
Fil- ħin ta ’ l- analiżi interim speċifikata minn qabel, il- punt aħħari primarju, iż- żmien għall- progressjoni intlaħaq u l- pazjenti fil- fergħa M+P saritilhom offerta għall- kura Vc+M+P.
Survival continued to be followed after the interim analysis.
Sopravivenza kompliet tiġi segwita wara l- analiżi interim.
Median follow-up was 16.3 months.
Żmien medjan ta ’ follow- up kien ta ’ 16. 3 xhur.
Efficacy results are presented in Table 7:
Riżultati ta ’ effikaċja huma ppreżentati f’ Tabella 8:
Summary of efficacy analyses in the VISTA study Efficacy endpoint Time to progression –
Żmien għall- progressjoni –
Events n (%) Mediana (95% CI)
Każijiet n (%)
Hazard ratiob
Medjana (95% CI)
(17.6, 24,7)
(17. 6, 24, 7)
(14.1, 17.9)
(14. 1, 17. 9)
(95% CI) p-value c Progression-free survival
(95% CI) Valur- p c Sopravivenza mingħajr progressjoni
(0.42, 0.70) 0.000002
(0. 42, 0. 70) 0. 000002
Events n (%) Mediana (95% CI)
Każijiet n (%) Medjana (95% CI)
135 (39) 18.3 mo
135 (39) 18. 3 mo
190 (56) 14.0 mo
190 (56) 14. 0 mo
Hazard ratiob
Proporzjon ta ’ periklub
(16.6, 21.7)
(16. 6, 21. 7)
(11.1, 15.0)
(11. 1, 15. 0)
(95% CI) p-value c Overall survival
(95% CI) Valur- p c Sopravivenza totali
(0.49, 0.76) 0.00001
(0. 49, 0. 76) 0. 00001
Events (deaths) n (%) Hazard ratiob (95% CI) c
Każijiet (imwiet) n (%) Proporzjon ta ’ periklub (95% CI) Valur- p c Rata ta ’ rispons popolazzjonie n = 668
0.61 (0.42, 0.88)
0. 61 (0. 42, 0. 88) 0. 00782
CR + PRf n (%) p-valued
CR + PR n (%) Valur- pd Tnaqqis tal- proteina M fis- serum g popolazzjoni n=667
238 (71)
238 (71) n=336
> =90% n (%) Time to first response in CR + PR
> =90% n (%) Żmien għall- ewwel rispons f’ CR + PR
Median a Median response duration
Medjan a Medjan ta ’ tul ta ’ żmien tar- rispons
1.4 mo
1. 4 mo
4.2 mo
4. 2 mo
CRf CR + PRf Time to next therapy
CRf CR + PRf Żmien għall- kura li jmiss
24.0 mo 19.9 mo
24. 0 mo 19. 9 mo
12.8 mo 13.1 mo
12. 8 mo 13. 1 mo
Events n (%) Mediana
Każijiet n (%) Medjana
127 (38) 20.8 mo
127 (38) 20. 8 mo
(95% CI) Hazard ratiob
(95% CI) Proporzjon ta ’ periklub
(26.1, NE)
(26. 1, NE)
(18.3, 28.5)
(18. 3, 28. 5)
(95% CI)
(95% CI) Valur- pc a Stima Kaplan- Meier. b
(0.39, 0.70)
(0. 39, 0. 70) 0. 000009
Kaplan-Meier estimate. b Hazard ratio estimate is based on a Cox proportional-hazard model adjusted for stratification factors: β 2-microglobulin, albumin, and region.
L- Istima tal- proporzjon tar- riskju hija bbażata fuq il- mudell Cox ta ’ riskju proporzjonali aġġustat għal fatturi ta ’ stratifikazzjoni: β2- mikroglobulina, albumina, u reġjun.
A hazard ratio less than 1 indicates an advantage for VMP c p-value based on the stratified log-rank test adjusted for stratification factors: beta2-microglobulin, albumin, and region d p-value for Response Rate (CR + PR) from the Cochran-Mantel-Haenszel chi-square test adjusted for the stratification factors e Response population includes patients who had measurable disease at baseline f EBMT criteria g All randomized patients with secretory disease
Proporzjon ta ’ riskju anqas minn 1 jindika vantaġġ għall- VMP c Valur- p ibbażat fuq it- test log- rank stratifikat aġġustat għal fatturi ta ’ stratifikazzjoni: beta2 - mikroglobulina, albumina, u reġjun. d Valur- p għar- Rata ta ’ Rispons (CR + PR) mit- test chi- square Cochran- Mantel- Haenszel aġġustat għal fatturi ta ’ stratifikazzjoni e Rispons tal- popolazzjoni jinkludi pazjenti li kellhom marda li titkejjel fil- linja bażi f Kriterji EBMT g Il- pazjenti randomized kollha b’ mard ta ’ sekrezzjoni
Not estimable
Ma jistax jiġi stmat
Clinical efficacy in relapsed or refractorymultiplemyeloma The safety and efficacy of VELCADE were evaluated in 2 studies at the recommended dose of 1.3 mg/ m2: a Phase III randomized, comparative study, versus dexamethasone (Dex), of 669 patients with relapsed or refractory multiple myeloma who had received 1-3 prior lines of therapy, and a Phase II single-arm study of 202 patients with relapsed and refractory multiple myeloma, who had received at least 2 prior lines of treatment and who were progressing on their most recent treatment.
Studji kliniċi f’ majloma multipla b’ episodju ġdid tagħha jew refrattorja Is- sigurtà u l- effikaċja ta ’ VELCADE kienu evalwati f’ 2 studji bid- doża rakkomandata ta ’ 1. 3 mg/ m2: studju random komparattiv ta ’ Fażi III kontra dexamethasone (Dex), ta ’ 669 pazjent b’ majloma multipla refrattorja jew b’ episodju ġdid tagħha li ħadu bejn 1 u 3 linji ta ’ terapija minn qabel, u studju ta ’ Fażi II b’ taqsima waħda b’ 202 pazjenti b’ majloma multipla refrattorja jew b’ episodju ġdid tagħha, li kienu ħadu mill- inqas 2 linji ta ’ terapija minn qabel u li kienu għaddejjin fuq l- iktar terapija reċenti.
(see Tables 9, 10 and 11).
(ara Tabelli 9, 10, u 11)
Dosing regimens in Phase II and Phase III studies Phase
Kuri ta ’ dożaġġ fl- istudji ta ’ Fażi II u Fażi III Fażi II
Treatment schedule
Skeda ta ’ kura Vc:
Dose
mistrieħ 12- 21)
Regimen
(estensjoni **)
Day 1,4,8,11, (rest Day 12-21) 1.3 mg/ m2 (intravenous bolus) Vc* 1.3 mg/ m2 a) Days 1,4,8,11, (Rest Day 12-21) (intravenous bolus) b) Days 1,8,15,22 Dex 40 mg (oral) a) Days 1– 4, 9 – 12, 17– 20Days 1– 4
Dex a) Jiem 1– 4, 9– 12, 17– 20 b) Jiem 1– 4
Q3 weeks x 8cycles (extension**) a) Q3weeks x 8, then b) Q5 weeks x 3 a) Q5 week x 4 b) Q4 week x 5
a) Q5 ġimgħa x 4 b) Q4 ġimgħa x 5
Add Dex*** 20 mg (oral) (Days 1,2,4,5,8,9, 11,12)
20 mg (mill- ħalq) (Jiem 1, 2, 4, 5, 8, 9, 11, 12)
Q3 weeks
Q3 ġimgħat
*a) is the initial treatment, a) and b) represent a full course of treatment **An extension study authorised patients benefiting from treatment to continue receiving VELCADE ***If after 2 or 4 cycles of VELCADE, the patients had progressive disease or stable disease, respectively, they could receive dexamethasone
a) huwa l- kura tal- bidu, a) u b) jirrappreżentaw il- kors kollu ta ’ kura ** Estensjoni ta ’ l- istudju awtorizza lil pazjenti li kienu qed jibbenefikaw mill- kura biex ikomplu jirċievu VELCADE *** Jekk wara 2 jew 4 ċikli ta ’ VELCADE, il- pazjenti kellhom mard progressiv jew mard stabbli, rispettivament, kienu jirċievu dexamethasone
Patient characteristics in Phase II and Phase III studies
Karatteristiċi tal- pazjenti fi studji ta ’ Fażi II u Fażi III
Phase II Vc
Fażi II Vc
Phase III Vc
Fażi III Vc
Phase III Dex
Fażi III Dex
Patient number, ITT analysis Male% Median age, yrs (range) Caucasian Karnofsky PS > 80% Platelets < 75,000/μ l Hemoglobin < 100g/ l Median Creatinine Clearance, ml/ min (range) 74
Numru ta ’ pazjenti, analiżi ITT% rġiel Età medja, snin (medda) Kawkażi Karnofsky PS > 80% Plejtlets < 75, 000/ μl
Myeloma IgG Myeloma IgA Myeloma light chain Median duration since diagnosis (yrs) Chromosome 13 abnormalities Median β 2-microglobulin (mg/ l) Median number prior treatment lines* (range)
(medda) Majloma IgG Majloma IgA Katina ħafifa tal- majloma Tul medju mid- djanjożi (snin) Anormalitajiet fil- Kromożomi 13 Medjan β2- mikroglobulina (mg/ l) Numru medju qabel il- linja ta ’ kura * (medda)
60% 24% 14% 4.0 15% 3.5 6 (2-15)
(14- 221) 60% 24% 14% 4. 0 15% 3. 5 6 (2- 15)
60% 23% 12% 3.5 25.7% 3.7 2 (1-7)
(15. 6- 170. 7) 60% 23% 12% 3. 5 25. 7% 3. 7 2 (1- 7)
59% 24% 13% 3.1 25.0% 3.6 2 (1-8)
(15. 3- 261. 1) 59% 24% 13% 3. 1 25. 0% 3. 6 2 (1- 8)
1 prior line > 1 prior line
1 linja ta ’ qabel > 1 linja ta ’ qabel
n =132 (40%) n = 186 (60%) n =
n = 132( 40%) n = 186 (60%)
n = 119 (35%) 194 (65%)
n = 119 (35%) n = 194 (65%)
*Including steroids, alkylating agents, anthracyclines, thalidomide and stem cell transplants
* Inklużi sterojdi, aġenti alkaliti, antraċiklini, thalidomide and trapjanti taċ- ċelluli staminali
16 Table 11:
16 Tabella 11:
Patient exposure to treatment with VELCADE during Phase II and III studies
Espożizzjoni tal- pazjenti għall- kura b’ VELCADE waqt studji ta ’ Fażi II u III
Received at least 1 dose Completed 4 cycles
Ħadu mill- inqas doża waħda Komlew 4 ċikli
a) all initial cycles (number) b) full course (number) c) extension *
a) ċikli kollha inizjali (numru) b) kors sħiħ (numru) c) estensjoni *
27% (8 cycles) NA N= 63 pts (median 7 cycles) or total median 14 cycles (range 7-32)
27% (8 ċikli) MA N= 63 punti (medja MA ta ’ 7 ċikli) jew total ta ’ medja ta ’ 14- il ċiklu (medda 7- 32)
29% (8 cycles) 9% (11 cycles) NA
29% (8 ċikli) 9% (11 ċikli)
36% (4 cycles) 5% (9 cycles) NA
36% (4 ċikli) 5% (9 ċikli) MA
*Patients could continue on treatment after completing 8 cycles, in case of benefit NA = not applicable
* Il- pazjenti setgħu ikomplu bil- kura wara li għamlu 8 ċikli, jekk il- kura kienet ta ’ benefiċċju MA = Mhux Applikabbli
In the Phase III study, treatment with VELCADE led to a significantly longer time to progression, a significantly prolonged survival and a significantly higher response rate, compared to treatment with dexamethasone (see Table 12), in all patients as well as in patients who have received 1 prior line of therapy.
Fl- istudju ta ’ Fażi III, il- kura b’ VELCADE wassal għal titwil sinifikanti tal- progressjoni, titwil sinifikanti ta ’ sopravivenza, u rata ogħla ta ’ rispons b’ mod sinifikanti, meta mqabbel mal- kura b’ dexamethasone (ara Tabella 12), fil- pazjenti kollha kif ukoll f’ pazjenti li kienu ħadu linja minn qabel ta ’ terapija.
As a result of a preplanned interim analysis, the Dexamethasone arm was halted at the recommendation of the data monitoring committee and all patients randomised to dexamethasone were then offered VELCADE, regardless of disease status.
Minħabba analiżi ad interim maħsuba minn qabel, il- parti b’ Dexamethasone twaqqfet wara rakkomandazzjoni tal- kumitat li kien qed jimmonitorja t- tagħrif, u l- pazjenti kollha li kienu qed jieħdu dexamethasone b’ mod random ġew offruti VELCADE, irrisprettivament mill- istat tal- marda.
Due to this early crossover, the median duration of follow-up for surviving patients is 8.3 months.
Minħabba din il- bidla bikrija fil- kura, it- tul medju tal- follow- up għall- pazjenti li kienu għadhom ħajjin kien ta ’ 8. 3 xhur.
Both in patients who were refractory to their last prior therapy and those who were not refractory, overall survival was significantly longer and response rate was significantly higher on the VELCADE arm.
Kemm fil- pazjenti li fl- aħħar terapija ta ’ qabel tagħhom kienu refrattarji u kemm dawk li ma kinux, is- sopravivenza kienu itwal b’ mod sinifikanti għal min kien qed jieħu VELCADE.
Of the 669 patients enrolled, 245 (37%) were 65 years of age or older.
Mis- 669 pazjent li daħlu għal dan l- istudju, 245 (37%) kellhom 65 sena jew iktar.
Response parameters as well as TTP remained significantly better for VELCADE independently of age.
Il- parametri ta ’ rispons kif ukoll it- TTP baqa ’ ogħla b’ mod sinifikanti irrispettivament mill- età.
Regardless of β 2- microglobulin levels at baseline, all efficacy parameters (time to progression and overall survival, as well as response rate) were significantly improved on the VELCADE arm.
Irrispettivament mill - livelli ta ’ β2 mikroglobulina fil- linja bażi, il- parametri kollha ta ’ effikaċja (żmien ta ’ progressjoni, sopravvivenza ġenerali, kif ukoll rata ta ’ rispons) tjiebu b’ mod sinifikattiv fil- parti ta ’ VELCADE ta ’ l- istudju.
In the refractory population of the Phase II study, responses were determined by an independent review committee and the response criteria were those of the European Bone Marrow Transplant Group.
Fil- popolazzjoni refrattorja ta ’ istudju ta ’ Fażi II, ir- rispons kien determinat minn kumitat indipendenti ta ’ verifika u l- kriterji ta ’ rispons kienu mal- Grupp Ewropew tat- Trapjant tal- Mudullun.
The median survival of all patients enrolled was 17 months (range < 1 to 36+ months).
Il- medja ta ’ sopravvivenza tal- pazjenti kollha kienet 17- il xahar (medda < 1 sa 36+ xahar).
This survival was greater than the six-to-nine month median survival anticipated by consultant clinical investigators for a similar patient population.
Din is- sopravvivenza kienet ikbar mill- medja ta ’ sopravvivenza ta ’ bejn 6 u 9 xhur antiċipata mill- investigaturi kliniċi konsulenti għal popolazzjoni simili ta ’ pazjenti.
By multivariate analysis, the response rate was independent of myeloma type, performance status, chromosome 13 deletion status, or the number or type of previous therapies.
B’ analiżi ‘ multivariate ’, ir- rata ta ’ rispons kienet indipendenti mit- tip ta ’ majloma, l- effett tal- kura, stat tat- tħassir tal- kromożomi, jew numru jew it- tip ta ’ terapiji ta ’ qabel.
Patients who had received 2 to 3 prior therapeutic regimens had a response rate of 32% (10/ 32) and patients who received greater than 7 prior therapeutic regimens had a response rate of 31% (21/ 67).
Pazjenti li kienu ħadu minn 2 sa 3 terapiji qabel kellhom rata ta ’ rispons ta ’ 32% (10/ 32) u pazjenti li kellhom iktar minn 7 terapiji minn qabel kellhom rata ta ’ rispons ta ’ 31% (21/ 67).
Summary of
Fażi III
disease outcomes from the Phase III and Phase II Phase III Phase III All patients 1 Prior line of therapy
Fażi III Linja waħda ta ’
studies Phase III > 1 Prior line of
Fażi III > Linja waħda ta ’
≥ 2
Fażi II ≥2 linji minn
Phase II prior
Il- pazjenti kollha
therapy
terapija minn qabel terapija minn qabel
lines
qabel
Time related
Episodji ta ’
events TTP, days
TTP, jiem
[148, 211]
211]
1 year survival,%
Sena waħda soppravvivenza
60
,%
[64,82]
L- aħjar
Best response
c
Dex Vc Dex Vc Dex
Vc Dex Vc Dex c
Dex Vc Dex Vc Dex
rispons (%)
Vc
n=110
Dex Vc Dex Vc Dex
n=187
41 (13) b
121 (38)
16 (13)
4 (4)
4 (4)
25 (13) 64 (34)
25 (13)
1 (< 1)
(10)**
CR+