qanastek/EMEA-V3 huggingface dataset:
Therapy should be discontinued if there is evidence of disease progression.
It- terapija għandha tiġi mwaqqfa jekk ikun hemm evidenza ta ’ progressjoni tal- marda.
In the event of serious infection or severe haematological toxicity MabCampath should be interrupted until the event resolves.
Fil- każ ta ’ infezzjoni serja jew tossiċità ematoloġika severa MabCampath għandu jiġi interrott sakemm il- każ jiġi riżolt.
It is recommended that MabCampath should be interrupted in patients whose platelet count falls to < 25,000/μ l or whose absolute neutrophil count (ANC) drops to < 250/μ l.
Huwa rrakkomandat li MabCampath għandu jiġi interrott f’ pazjenti li l - għadd tal- plejtlits tagħhom jinżel għal < 25, 000/ μl jew li l- għadd assolut ta 'newtrofili (ANC) jinżel għal < 250/ μl.
MabCampath may be reinstituted after the infection or toxicity has resolved.
MabCampath jista ’ jiġi mogħti mill- ġdid wara li l- infezzjoni jew it- tossiċità tkun ġiet riżolta.
MabCampath should be permanently discontinued if autoimmune anaemia or autoimmune thrombocytopenia appears.
MabCampath għandu jitwaqqaf b' mod permanenti jekk titfaċċa anemija awtoimmuni jew tromboċitopenija awtoimmuni.
The following table outlines the recommended procedure for dose modification following the occurrence of haematological toxicity while on therapy:
It- tabella li ġejja tiddeskrivi l- proċedura rrakkomandata għal modifikazzjoni tad- doża wara każ ta ’ tossiċità ematoloġika waqt it- terapija:
ANC < 250/μ L and/ or platelet count ≤ 25,000/μ L
Modifikazzjoni fid- Doża * Valuri Ematoloġiċi ANC < 250/ μL u/ jew għadd ta ’ plejtlits ta ’ ≤25, 000/ μL
For first occurrence:
Għall- ewwel okkorrenza:
Withhold MabCampath therapy.
Waqqaf it- terapija ta ’ MabCampath.
Resume MabCampath at 30 mg when ANC ≥ 500/μ L and platelet count ≥ 50,000/μ L.
Kompli MabCampath b’ 30 mg meta l- ANC huwa ≥ 500/ μL u l- għadd ta ’ plejtlits huwa ≥ 50, 000/ μL.
For second occurrence:
Għat- tieni okkorrenza:
Resume MabCampath at 10 mg when ANC ≥ 500/μ L and platelet count ≥ 50,000/μ L.
Kompli MabCampath b’ 10 mg meta l- ANC huwa ≥ 500/ μL u l- għadd ta ’ plejtlits huwa ≥ 50, 000/ μL.
For third occurrence:
Għat- tielet okkorrenza:
Discontinue MabCampath therapy.
Waqqaf għal kollox it- terapija ta ’ MabCampath.
≥ 50% decrease from baseline in patients initiating therapy with a baseline ANC ≤ 250/μ L and/ or a baseline platelet count ≤ 25,000/μ L
Tnaqqis ta ’ ≥ 50% mil- linja bażi f’ pazjenti li ħa jibdew it- terapija b’ ANC fil- linja bażi ta ’ ≤ 250/ μL u/ jew għadd ta ’ plejtlits fil- linja bażi ta ’ ≤ 25, 000/ μL
Resume MabCampath at 30 mg upon return to baseline value(s).
Kompli MabCampath b’ 30 mg hekk kif jirritornaw għall- valur( i) fil- linja bażi.
Resume MabCampath at 10 mg upon return to baseline value(s).
Kompli MabCampath b’ 10 mg hekk kif jirritornaw għall- valur( i) fil- linja bażi.
*If the delay between dosing is ≥ 7 days, initiate therapy at MabCampath 3 mg and escalate to 10 mg and then to 30 mg as tolerated
* Jekk id- dewmien bejn id- dożaġġ huwa ≥ 7 ġranet, ibda ’ t- terapija b’ MabCampath 3 mg u żid għal 10 mg u wara għal 30 mg skond kif ikun ittollerat M’ hemm l- ebda modifikazzjonijiet fid- doża rrakkomandati għal limfopenja severa minħabba l - mekkaniżmu t’ azzjoni ta ’ MabCampath.
Children and adolescents (below 17 years of age):
Tfal u adoloxxenti (taħt l- età ta ’ 17- il sena):
No studies have been conducted.
L- ebda studju ma ġie mwettaq.
MabCampath is not recommended for use in the paediatric age group.
MabCampath mhux irrakkomandat għall- użu fil- grupp ta ’ età pedjatrika.
Elderly (over 65 years of age):
Anzjani ('l fuq minn 65 sena):
Recommendations are as stated above for adults.
Ir- rakkomandazzjonijiet huma kif dikjarati fuq għall- adulti.
Patients should be monitored carefully (see section 4.4).
Il- pazjenti għandhom jiġu sorveljati b’ attenzjoni (ara sezzjoni 4. 4).
Patients with renal or hepatic impairment:
Pazjenti b 'indeboliment tal- kliewi jew tal- fwied:
3 No studies have been conducted.
3 L- ebda studju ma ’ ġie mwettaq.
- hypersensitivity to alemtuzumab, to murine proteins or to any of the excipients;
- sensittività eċċessiva għal alemtuzumab, għall- proteini murini jew għal xi sustanzi mhux attivi
- patients with active systemic infections;
- pazjenti b’ infezzjonijiet sistemiċi attivi;
- patients infected with HIV;
- pazjenti nfettati bl- HIV;
- patients with active second malignancies;
- pazjenti b’ tumuri malinni attivi oħrajn;
- pregnancy.
- tqala
Acute adverse reactions, which may occur during initial dose escalation and some of which may be due to the release of cytokines, include hypotension, chills/ rigors, fever, shortness of breath and rashes.
Reazzjonijiet avversi akuti li jistgħu jseħħu hekk kif tinbeda doża ogħla u li wħud minnhom jistgħu jkunu minħabba r- reħa ta ’ cytokine jinkludi pressjoni baxxa, sirdat/ tertir, deni, nuqqas ta ’ nifs u raxx.
Additional reactions include nausea, urticaria, vomiting, fatigue, dyspnoea, headache, pruritus, diarrhoea and bronchospasm.
Reazzjonijiet oħrajn jinkludu tqalligħ, urtikarja, rimettar, għeja, qtugħ ta ’ nifs, uġigħ ta ’ ras, ħakk, dijarea u bronkospażmu.
The frequency of infusion reactions was highest in the first week of therapy, and declined in the second or third week of treatment, in patients treated with MabCampath both as first line therapy and in previously treated patients.
Il- frekwenza ta ’ reazzjonijiet ta ’ l- infużjoni kienu l- ogħla fl- ewwel ġimgħa ta ’ kura u naqsu fit- tieni u t- tielet ġimgħa ta ’ kura, f’ pazjenti kkurati b’ MabCampath kemm bħala t - terapija preferita kif ukoll f’ pazjenti kkurati qabel.
If these events are moderate to severe, then dosing should continue at the same level prior to each dose escalation, with appropriate premedication, until each dose is well tolerated.
Jekk dawn l- avvenimenti huma moderati sa severi, d- dożaġġ għandu jissokta bl- istess livell qabel kull żjieda fid- doża, b’ kura minn qabel xierqa, sakemm kull doża tkun ittollerata sew.
If therapy is withheld for more than 7 days, MabCampath should be reinstituted with gradual dose escalation.
Jekk it- terapija tiġi miżmuma għal aktar minn 7 ijiem, MabCampath għandu jigi ristabbilit b’ żjieda gradwali fid- doża.
Transient hypotension has occurred in patients receiving MabCampath.
Pressjoni baxxa li tgħaddi seħħet f’ pazjenti li ħadu MabCampath.
Caution should be used in treating patients with ischaemic heart disease, angina and/ or in patients receiving an antihypertensive medicinal product.
Għandu jkun hemm kawtela fil- kura ta ’ pazjenti b’ mard iskemiku tal- qalb, anġina u/ jew f’ pazjenti li qed jirċievu prodott mediċinali kontra l- pressjoni għolja.
Myocardial infarction and cardiac arrest have been observed in association with MabCampath infusion in this patient population.
Infart mijokardijaku u arrest kardijaku ġew osservati f’ assoċjazzjoni ma ’ infużjoni ta ’ MabCampath f’ din il- popolazzjoni ta 'pazjenti.
Assessment and ongoing monitoring of cardiac function (e. g. echocardiography, heart rate and body weight) should be considered in patients previously treated with potentially cardiotoxic agents.
Valutazzjoni u sorveljanza kostanti tal- funzjoni tal- qalb (e. g. ekokardjografija, rata tal- qalb u piż tal - ġisem) għandhom jiġu kkonsidrati f' pazjenti li qabel kienu kkurati b' mediċini li setgħu kienu kardjotossiċi.
It is recommended that patients be premedicated with oral or intravenous steroids 30 - 60 minutes prior to each MabCampath infusion during dose escalation and as clinically indicated.
Huwa rrakkomandat li pazjenti jkunu kkurati minn qabel bi sterojdi orali jew fil- vini 30- 60 minuta qabel kull infużjoni ta ’ MabCampath waqt żjieda fid- doża u kif indikat klinikament.
Steroids may be discontinued as appropriate, once dose escalation has been achieved.
Sterojdi jistgħu jitwaqqfu kif xieraq la darba l- ogħla doża tkun intlaħqet.
In addition, an oral antihistamine, e. g. diphenhydramine 50 mg, and an analgesic, e. g. paracetamol 500 mg, may be given.
Barra dan, jistgħu jingħataw ukoll antistamina orali e. ż. diphenhydramine 50 mg, u analġeżiku e. ż. paracetamol 500.
In the event that acute infusion reactions persist, the infusion time may be extended up to 8 hours from the time of reconstitution of MabCampath in solution for infusion.
F’ każ li r - reazzjonijiet akuti għall- infużjoni jippersistu, il- ħin ta ’ infużjoni jista ’ jiġi estiż għal sa 8 sigħat mill - ħin ta ’ rikostituzzjoni ta ’ MabCampath f’ soluzzjoni għall- infużjoni.
Profound lymphocyte depletion, an expected pharmacological effect of MabCampath, inevitably occurs and may be prolonged.
Tnaqqis sostanzjali tal- limfoċiti, effett farmakologiku mistenni ta ’ MabCampath, jiġri inevitabbilment u jista ’ jdum.
CD4 and CD8 T-cell counts begin to rise from weeks 8-12 during treatment and continue to recover for several months following the discontinuation of treatment.
L- għadd ta ’ ċelluli- T CD4 u CD8 jibda jogħla minn 8 ġimgħat sa 12- il ġimgħa waqt il - kura u jkompli jirkupra għal diversi xhur wara li titwaqqaf il- kura.
In patients receiving MabCampath as first line therapy, the recovery of CD4+ counts to ≥ 200 cells/ µl occurred by 6 months post-treatment, however, at 2 months post-treatment the median was 183 cells/μ l.
F’ pazjenti li jirċievu MabCampath bħala terapija preferita, l- irkupru ta ’ l- għadd ta ’ CD4+ għal ≥200 ċellula/ µl seħħ sa 6 xhur wara l- kura, madankollu, fi żmien xahrejn wara l- kura l- medjan kien ta ’ 183 ċellula/ µl.
In previously treated patients receiving MabCampath, the median time to reach a level of 200 cells/μ l is 2 months following last infusion with MabCampath but may take more than 12 months to approximate pretreatment levels.
F’ pazjenti kkurati qabel li kienu qed jirċievu MabCampath il- ħin medjan sabiex jintlaħaq livell ta ’ 200 ċellula/ μl huwa ta ’ xahrejn wara l- aħħar infużjoni ta ’ MacCampath iżda jista ’ jieħu aktar minn 12- il xahar biex jintlaħqu l- livelli approssimattivi ta ’ qabel il- kura.
This may predispose patients to opportunistic infections.
Dan jista ’ jippredisponi lill- pazjenti għall- infezzjonijiet opportunistiċi.
It is highly recommended that anti-infective prophylaxis (e. g. trimethoprim/ sulfamethoxazole 1 tablet twice daily, 3 times weekly, or other prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and an effective oral anti-herpes agent, such as famciclovir, 250 mg twice daily) should be initiated while on therapy and for a minimum of 2 months following completion of treatment with MabCampath or until the CD4+ count has recovered to 200 cells/μ l or greater, whichever is the later.
Hija rrakkomandata ħafna li tiġi mibdija profilassi anti- infettiva waqt it- terapija (e. ż. pillola waħda darbtejn kuljum, tliet darbiet fil- ġimgħa ta ’ trimethoprim/ sulfamethoxazole, jew profilassi oħra kontra il- pnewmonja Pneumocystis jiroveci (PCP) u mediċina orali effettiva kontra l - herpes bħal famciclovir, 250 mg darbtejn kuljum) u għal ta ’ l- inqas xagħrejn wara li l- kura b’ MabCampath tkun tlestiet jew sakemm l- għadd totali ta ’ CD4+ ikun irkupra għal 200 ċellula/ μl jew aktar, skond liema jiġi l- aħħar.
Because of the potential for Transfusion Associated Graft Versus Host Disease (TAGVHD) it is recommended that patients who have been treated with MabCampath receive irradiated blood products.
Minħabba l- possibiltà ta ’ Transfusion Associated Graft Versus Host Disease (TAGVHD), huwa rrakkomandat li pazjenti li kienu ikkurati b’ MabCampath jirċievu prodotti tad- demm irradjati.
4 Asymptomatic laboratory positive Cytomegalovirus (CMV) viraemia should not necessarily be considered a serious infection requiring interruption of therapy.
4 Viremija kkawżata minn cytomegalovirus (CMV) mhix sintomatika iżdaa pożittiva fil- laboratorju m’ għandhiex bilfors tiġi kkunsidrata bħala infezzjoni serja li teħtieġ li t- terapija tiġi interrotta.
Ongoing clinical assessment should be performed for symptomatic CMV infection during MabCampath treatment and for at least 2 months following completion of treatment.
Għandha titwettaq valutazzjoni klinika li tibqa ’ għaddejja għall- infezzjoni sintomatika ta ’ CMV waqt kura b’ MabCampath u għal ta ’ lanqas xahrejn wara li tintemm il- kura.
Transient grade 3 or 4 neutropenia occurs very commonly by weeks 5-8 following initiation of treatment.
Newtropenija li tgħaddi ta ’ Grad 3 jew 4 isseħħ ta ’ spiss ħafna 5- 8 ġimgħat wara l- bidu tal- kura.
Transient grade 3 or 4 thrombocytopenia occurs very commonly during the first 2 weeks of therapy and then begins to improve in most patients.
Tromboċitopenija li tgħaddi ta ’ grad 3 jew 4 isseħħ b’ mod komuni ħafna waqt l- ewwel ġimagħtejn ta ’ terapija u mbagħad tibda tmur għal aħjar fil- biċċa l- kbira tal- pazjenti.
Therefore, haematological monitoring of patients is indicated.
Għalhekk, hija ndikata sorveljanza ematoloġika tal- pazjenti.
If a severe haematological toxicity develops, MabCampath treatment should be interrupted until the event resolves.
Jekk tiżviluppa tossiċità ematoloġika severa, kura b’ MabCampath għandha tiġi nterrotta sakemm il- każ jiġi riżolt.
MabCampath treatment may be reinstituted following resolution of the haematological toxicity (see section 4.2).
Il- kura b’ MabCampath tista ’ terġa ’ tibda mill- ġdid wara li tkun riżolta t- tossiċità ematoloġika (ara sezzjoni 4. 2).
Complete blood counts and platelet counts should be obtained at regular intervals during MabCampath therapy and more frequently in patients who develop cytopenias.
L- għadd sħiħ ta ’ ċelluli fid- demm u l- għadd ta ’ plejtlits għandhom jittieħdu f’ intervalli regolari waqt it- terapija b’ MabCampath u aktar ta ’ spiss f’ pazjenti li jiżviluppaw ċitopeniji.
It is not proposed that regular and systematic monitoring of CD52 expression should be carried out as routine clinical practice.
Mhux qed jiġi propost li sorveljanza sistematika u regolari ta ’ l- espressjoni ta ’ CD52 għandha titwettaq bħala prattika klinika regolari.
However, if retreatment is considered, it may be prudent to confirm the presence of CD52 expression.
Madankollu, jekk tiġi kkunsidrata kura mill- ġdid, ikun prudenti li tiġi kkonfermata l- preżenza ta ’ l- espressjoni ta ’ CD52.
In data available from first line patients treated with MabCampath, loss of CD52 expression was not observed around the time of disease progression or death.
F’ tagħrif disponibbli minn pazjenti kkurati b’ MabCampath bħala l- mediċina preferita, telf ta ’ l- espressjoni ta ’ CD52 ma kienx osservat fil- ħin tal- progressjoni tal- marda jew il- mewt.
Patients may have allergic or hypersensitivity reactions to MabCampath and to murine or chimeric monoclonal antibodies.
Pazjenti jista ’ jkollhom reazzjonijiet allerġiċi jew ta ’ sensittività eċċessiva għal MabCampath u għal antikorpi monoklonali murini jew kimeriċi.
Medicinal products for the treatment of hypersensitivity reactions, as well as preparedness to institute emergency measures in the event of reaction during administration is necessary (see section 4.2).
Prodotti mediċinali għall- kura ta 'reazzjonijiet ta' sensittività eċċessiva, kif ukoll preparament sabiex isiru interventi ta 'emerġenza f' każ ta' reazzjoni waqt l- għoti huma meħtieġa (ara sezzjoni 4. 2).
Males and females of childbearing potential should use effective contraceptive measures during treatment and for 6 months following MabCampath therapy (see sections 4.6 and 5.3).
Nisa u rġiel li jista ’ jkollhom it- tfal għandhom jużaw miżuri effettivi ta ’ kontraċezzjoni waqt il- kura u għal sitt xhur wara li jtemmu t- terapija b' MabCampath (ara sezzjonijiet 4. 6 u 5. 3).
No studies have been conducted which specifically address the effect of age on MabCampath disposition and toxicity.
Ma saru l- ebda studji li jindirizzaw b' mod speċifiku l- effett ta 'l- età fuq id- dispożizzjoni u t- tossiċità ta ’ MabCampath.
In general, older patients (over 65 years of age) tolerate cytotoxic therapy less well than younger individuals.
B’ mod ġenerali, pazjenti anzjani (b’ età `l fuq minn 65 sena) jittolleraw it- terapija ċitotossika ferm inqas minn individwi iżgħar.
Since CLL occurs commonly in this older age group, these patients should be monitored carefully (see section 4.2).
Peress li CLL hija aktar komuni f' dan il- grupp ta ’ etajiet akbar, dawn il- pazjenti għandhom jiġu sorveljati b' attenzjoni (ara sezzjoni 4. 2).
In the studies in first line and previously treated patients no substantial differences in safety and efficacy related to age were observed; however the sizes of the databases are limited.
Fl- istudji f’ pazjenti kkurati għall- ewwel darba u pazjenti kkurati qabel ma kienux osservati differenzi sostanzjali fis - sigurtà u l- effikaċja relatati ma ’ l- età, madankollu d- daqsijiet tat- tagħrif huma ristretti.
Although no formal drug interaction studies have been performed with MabCampath, there are no known clinically significant interactions of MabCampath with other medicinal products.
Għalkemm ma sarux studji formali dwar l- interazzjonijiet b' MabCampath, mhux magħrufa interazzjonijiet ta ’ sinifikanza klinika ta ’ MabCampath ma ’ prodotti mediċinali oħra.
Because MabCampath is a recombinant humanized protein, a P450 mediated drug-drug interaction would not be expected.
Peress li Mabcampath huwa proteina rikombinanti umanizzat, interazzjoni ta ’ mediċina ma ’ mediċina permezz ta ’ P450 mhix mistennija.
However, it is recommended that MabCampath should not be given within 3 weeks of other chemotherapeutic agents.
Madankollu, huwa rrakkomandat li MabCampath m’ għandux jingħata fi żmien 3 ġimgħat wara t- teħid ta ’ sustanzi kimoterapewtiċi oħra.
Although it has not been studied, it is recommended that patients should not receive live viral vaccines in, at least, the 12 months following MabCampath therapy.
Għalkemm għadu ma ġiex studjat, huwa rrakkomandat li pazjenti m' għandhomx jirċievu vaċċini tal- viri ħajjin qabel ta ’ l- anqas, 12- il xahar wara li tintemm it- terapija b' MabCampath.
The ability to generate a primary or anamnestic humoral response to any vaccine has not been studied.
Il- ħila ta ’ ġenerazzjoni ta ’ rispons primarju jew rispons umurali anamnestiku għal kwalunkwe vaċċin għadu ma ġiex studjat.
MabCampath is contraindicated during pregnancy.
5 MabCampath huwa kontra- indikat waqt it- tqala.
Human IgG is known to cross the placental barrier; MabCampath may cross the placental barrier as well and thus potentially cause foetal B and T cell lymphocyte depletion.
IgG uman huwa magħruf li jgħaddi mill- barriera tas- sekonda; MabCampath jista ’ jgħaddi mill- barriera tas- sekonda u b’ hekk jista 'jikkaġuna tnaqqis limfoċetiku taċ- ċelluli B u T tal- fetu.
It is
Ma sarux studji dwar ir- riproduzzjoni fl - annimali b' MabCampath.
5 not known whether MabCampath can cause foetal harm when administered to a pregnant woman or whether it can affect reproductive capacity.
Mhux magħruf jekk MabCampath jistax jikkaġuna ħsara fil- fetu meta jingħata lil nisa tqal jew jekk jistax jaffetwa l- kapaċità riproduttiva.
Males and females of childbearing capacity should use effective contraceptive measures during treatment and for 6 months following MabCampath therapy.
Irġiel u nisa li jista ’ jkollhom it- tfal għandhom jużaw miżuri effettivi ta ’ kontraċezzjoni waqt il- kura u sa sitt xhur wara t- terapija b' MabCampath.
It is not known whether MabCampath is excreted in human milk.
Mhux magħruf jekk MabCampath huwiex eliminat fil- ħalib tal- bniedem.
If treatment is needed, breast-feeding should be discontinued during treatment and for at least 4 weeks following MabCampath therapy.
Jekk il- kura hija meħtieġa, t - treddigħ għandu jitwaqqaf waqt il- kura u għal ta ’ l- anqas 4 ġimgħat wara li tintemm it- terapija b' MabCampath.
However, caution should be exercised as confusion and somnolence have been reported.
Madankollu, għandu jkun hemm attenzjoni peress li ġew irrapportati każijiet ta 'konfużjoni u ngħas.
The tables below report adverse reactions by MedDRA system organ classes (MedDRA SOCs).
It- tabelli taħt jirrapportaw reazzjonijiet avversi skond is- sistema tal- klassifika ta ’ l- organi MedDRA (MedDRA SOC).
The frequencies are based on clinical trial data.
Il- frekwenzi huma bbażżati fuq tagħrif minn provi kliniċi.
The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.
L- aktar terminu xieraq ta ’ MedDra qed jintuża sabiex jiddeskrivi ċertu reazzjoni u s- sinonimi u l - kondizzjonijiet relatati miegħu.
The frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100).
Il- frekwenzi huma definiti bħala: komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100 sa < 1/ 10), mhux komuni (≥ 1/ 1, 000 sa < 1/ 100).
No information is available for events that occur at lower frequency, due to the size of the population studied; n=147 for first line treated patients and n=149 for previously treated patients.
L- ebda informazzjoni ma hija disponibbli għal każijiet li jseħħu fi frekwenza aktar baxxa, minħabba d- daqs tal- popolazzjoni studjata; n=147 għal pazjenti kkurati l- ewwel darba u n=149 għal pazjenti kkurati qabel.
Undesirable effects in first line patients
Effetti mhux mixtieqa għal pazjenti kkurati l- ewwel darba
Safety data in first-line B-CLL patients are based on adverse reactions that occurred on study in 147 patients enrolled in a randomized, controlled study of MabCampath as a single agent administered at a dose of 30 mg intravenously three times weekly for up to 12 weeks, inclusive of dose escalation period.
Tagħrif dwar is- sigurtà f’ pazjenti b’ B- CLL ikkurati l- ewwel darba huwa bbażat fuq reazzjonijiet avversi li seħħew waqt l- istudju b’ 147 pazjent rekrutati fi studju randomised, b’ kontrolli, ta ’ MabCampath bħala s- sustanza unika mogħti f’ doża ta ’ 30 mg ġol- vini tliet darbiet fil- ġimgħa sa 12- il ġimgħa, inkluż iż- żmien li d- doża titqawwa.
Approximately 97% of first-line patients experienced adverse reactions; the most commonly reported reactions in first line patients usually occurred in the first week of therapy.
Madwar 97% tal- pazjenti ikkurati għall- ewwel darba kellhom reazzjonijiet avversi: l- aktar reazzjonijiet irrapportati b’ mod komuni f’ pazjenti ikkurati għall - ewwel darba ġeneralment seħħew fl- ewwel ġimgħa ta ’ terapija.
Within each frequency grouping, undesirable effects observed during treatment or within 30 days following the completion of treatment with MabCampath are presented in order of decreasing seriousness.
L- effetti li huma l- aktar serji huma mniżżla l- ewwel, segwiti minn dawk anqas serji.
6 SYSTEM ORGAN CLASS MEDDRA
6 Sistema tal- Klassifika tal- Organi MedDRA
VERY
Komuni ħafna
COMMON COMMON
Komuni
UNCOMMON
Mhux komuni
Cytomegalovirus viraemia
Cytomegalovirus viremija
Pneumonia
Pnewmonja
Cytomegalovirus infection
Infezzjoni b ’ cytomegalovirus
Bronchitis Pharyngitis Oral candidiasis
Bronkite Farinġite Kandidajasi orali
Staphylococcal bacteraemia Tuberculosis Bronchopneumonia Herpes ophthalmicus Beta haemolytic streptococcal infection Candidiasis Genital candidiasis Urinary tract infection Cystitis Body tinea Nasopharyngitis Rhinitis
Batterimja kkawżata minn Staphyloccus Tuberkulosi Bronkopnewmonja Herpes ophthalmicus Infezzjoni emolitika beta kkawżata minn streptococcus Kandidajasi Kandidajasi ġenitali Infezzjoni fl- apparat urinarju Ċistite Tinea tal- ġisem Nasofarinġite Rinite
Blood and lymphatic system disorder
Disturbi tad- demm u tas- sistema limfatika
Febrile neutropenia Neutropenia Leukopenia Thrombocytopenia Anaemia
Newtropenija bid- deni Newtropenija Lewkopenija Tromboċitopenija Anemija
Agranulocytosis Lymphopenia Lymphadenopathy Epistaxis
Agranuloċitosi Limfopenija Limfoadenopatija Epistassi
Anaphylactic reaction Hypersensitivity
Reazzjoni anafilattika Sensittività eċċessiva
Metabolic and nutrition disorders
Disturbi fil - metaboliżmu u n - nutrizzjoni
Tumour lysis syndrome Hyperglycaemia Protein total decreased Anorexia
Sindrome tad - disintegrazzjoni tat- tumur Ipergliċemija Total tal- proteina mnaqqas Anoreksja
Syncope Dizziness Tremor Paraesthesia Hypoesthesia Headache
Sinkope Sturdament Tertir Parastesija Ipoestesija Uġigħ ta ’ ras
Cyanosis Bradycardia Tachycardia Sinus tachycardia
Ċjanożi Bradikardja Takikardja Sinus takikardja
Cardiac arrest Myocardial infarction Angina pectoris Atrial fibrillation Arrhythmia supraventricular Sinus bradycardia Supraventricular extrasystoles
Arrest kardijaku Infart mijokardijaku Anġina pektoris Fibrillazzjoni atrijali Arritmija supraventrikulari Sinus bradikardja Ekstrasistoles supraventrikulari
Respiratory, thoracic and mediastinal disorders
Pressjoni ortostatika baxxa Fwawar ta ’ sħana
7
7 Fwawar Disturbi respiratorji, toraċiċi u medjastinali
Bronchospasm Dyspnoea
Bronkospażmu Qtugħ ta ’ nifs
Hypoxia Pleural effusion Dysphonia
Ipoksja Effużjoni fil- plewra Disfonija Rinoreja
Gastrointestinal
Disturbi gastro - intestinali
disorders
Tqalligħ
Oral discomfort Stomach discomfort Diarrhoea
Rimettar Uġigħ addominali
Skin and subcutaneous tissue disorders
Ileus Skomdu fil- ħalq Taqlib fl- istonku Dijarea
Dermatitis allergic
Disturbi fil- ġilda u fit - tessuti ta ’ taħt il- ġilda
Rash pruritic
Urtikarja Raxx
Pruritus Hyperhidrosis Erythema
Dermatite allerġika Ħakk Iperidrosi Eritema
Rash macular Rash erythematous Dermatitis
Raxx bil- ħakk Raxx makulari Raxx eritematuż Dermatite
Myalgia Musculoskeletal pain Back pain
Mijalġja Uġigħ muskolu - skeltrali Uġigħ fid- dahar
Bone pain Arthralgia Musculoskeletal chest pain Muscle spasms
Uġigħ fl- għadam Artralġja Uġigħ muskolu- skeltrali fis- sider Spażmi fil- muskoli
Urine output decreased Dysuria
Infjammazzjoni fil- mukosa
General disorders and administration site conditions
mnejn jingħata
Fever Chills
Sirdat
Fatigue Asthenia
Astenja
Mucosal inflammation Infusion site erythema Localised oedema Infusion site oedema Malaise
Eritema fis- sit ta ’ l- infużjoni Edima lokalizzata Edima fis- sit ta ’ l- infużjoni Tħossok ma tiflaħx
Acute infusion reactions including fever, chills, nausea, vomiting, hypotension, fatigue, rash, urticaria, dyspnoea, headache, pruritus and diarrhoea have been reported.
Kienu rrapportati reazzjonijiet akuti għall- infużjoni, inkluż deni, sirdat, tqalligħ, rimettar, pressjoni baxxa, għeja, raxx, uritkarja, qtugħ ta ’ nifs, uġigħ ta ’ ras, ħakk u dijarea.
The majority of these reactions are mild to moderate in severity.
Il- maġġoranza ta ’ dawn ir - reazzjonijiet huma ta ’ severità ħafifa sa moderata.
Acute infusion reactions usually occur during the first week of therapy and substantially decline thereafter.
Reazzjonijiet akuti għall- infużjoni ħafna drabi jseħħu fl- ewwel ġimgħa ta ’ terapija u wara jonqsu sostanzjalment.
Grade 3 or 4 infusion reactions are uncommon after the first week of therapy.
Wara l- ewwel ġimgħa ta ’ terapija, reazzjonijiet għall- infużjoni ta ’ grad 3 jew 4 mhumiex komuni.
Undesirable effects in previously treated patients
Effetti mhux mixtieqa f’ pazjenti kkurati qabel
Safety data in previously treated B-CLL patients are based on 149 patients enrolled in single-arm studies of MabCampath (Studies 1, 2, and 3).
Tagħrif dwar is- sigurtà f’ pazjenti b’ B- CLL kkurati qabel huwa bbażżat fuq 149 pazjent rekrutat fi studji single arm ta ’ MabCampath (Studji 1, 2 u 3).
More than 80% of previously treated patients may be expected to experience adverse reactions; the most commonly reported reactions usually occur during the first week of therapy.
Aktar minn 80% ta ’ pazjenti kkurati minn qabel huma mistennija li jkollhom reazzjonijiet avversa: l- aktar reazzjonijiet irrapportati b’ mod komuni ġeneralment iseħħu fl- ewwel ġimgħa ta ’ terapija.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżla skond is- serjetà tagħhom.
SYSTEM ORGAN CLASS MEDDRA
8 SISTEMA TAL - KLASSIFIKA TAL - ORGANI MEDDRA
VERY
KOMUNI ĦAFNA
COMMON COMMON
KOMUNI
UNCOMMON
MHUX KOMUNI Infezzjoni kkawżata minn batterja
Cytomegalovirus infection
Infezzjoni kkawżata minn Cytomegaloviru s
Bacterial infection
Infezzjoni virali
Pneumocystis jiroveci infection
Infezzjoni Pneumocystis jiroveci
Pneumonitis Fungal infection Candidiasis Herpes zoster Abscess
Pnewmonite Infezzjoni kkawżata minn fungi
Fungal dermatitis Laryngitis Rhinitis Onychomycosis
Dermatite kkawżata minn fungi Larinġite
8
Neoplażmi, beninni, malinni u dawk mhux speċifikati (inkluż ċesti u polipi)
Urinary tract infection Sinusitis Bronchitis Upper respiratory tract infection Pharyngitis Infection Neoplasms, benign, malignant and unspecified (incl. cysts and polyps)
Kandidajasi Herpes zoster Axxess Infezzjoni fl- apparat urinarju Sinusite Bronkite Infezzjoni fl- apparat respiratorju ta 'fuq Faringite Infezzjoni
Lymphoma – like disorder
Rinite Onikomikożi Disturbi bħal limfoma
Blood and lymphatic system disorder
Disturbi tad- demm u
Granulocytopenia Thrombocytopenia
Aplasja tal- mudullun tal- għadam
Febrile neutropenia Pancytopenia
tas- sistema limfatika
Aplasia bone marrow Disseminated intravascular coagulation
Koagulazzjoni intravaskulari mifruxa
Leukopenia
Lewkopenija
Haemolytic anaemia, Decreased haptoglobin
Anemija emolitika, Ħaptoglobin imnaqqas
Bone marrow depression Epistaxis Gingival bleeding Haematology test abnormal
Mudullun imrażżan Epistassi Fsada mill- ħanek Test ematoloġiku mhux normali
Allergic reaction Severe anaphylactic and other hypersensitivity reactions
Reazzjoni allerġika Reazzjonijiet anafilattiċi severi u reazzjonijiet ta ’ sensittività eċċessiva oħra
Metabolic and nutrition disorders
Disturbi fil - metaboliżmu u n - nutrizzjon
Hyponatraemia Hypocalcaemia Weight decrease Dehydration Thirst
Iponatrimija Ipokalċimija Tnaqqis fil- piż Deidrazzjoni Għatx
Hypokalaemia Diabetes mellitus aggravated
Ipokalimja Dijabete mellitus taggrava
Psychiatric disorders
Disturb fil- personalità
Confusion Anxiety Depression Somnolence Insomnia
Depressjoni Ħedla Insomnija
Depersonalisation Personality disorder Abnormal thinking Impotence Nervousness
Ħsibijiet mhux normali Impotenza Nervi
Vertigo Dizziness Tremor Paresthesia Hypoesthesia Hyperkinesia Taste loss
Vertiġo Sturdament Rogħda Parastesja Ipoestesija Iperkinesja Telf tat- togħma
Syncope Abnormal gait Dystonia Hyperesthesia Neuropathy Taste perversion
Sinkope Mixja mhux normali Distonja Iperestisja Newropatija Perverżjoni tat- togħma
Eye disorders Ear and labyrinth disorders
Disturbi fl- għajnejn
Endophthalmitis Deafness Tinnitus
Truxija Tinnitus
Palpitation Tachycardia
Palpitazzjoni Takikardja
Cardiac arrest Myocardial infarction Atrial fibrillation Supraventricular tachycardia Arrhythmia Bradycardia Abnormal ECG
Arrest kardijaku Infart mijokardijaku Fibrillazzjoni atrijali Takikardja supraventrikulari Arritimija Bradikardja ECG mhux normali
Hypertension Vasospasm Flushing
Pressjoni għolja Vażospażmu Fwawar
Peripheral ischaemia
Iskemija periferali
Hypoxia Haemoptysis Bronchospasm Coughing
Ipoksja Emoptisi Bronkspażmu Sogħla
Stridor Throat tightness Pulmonary infiltration Pleural effusion Breath sounds decreased Respiratory disorder
Stridor Griżmejn jingħalqu Infiltrazzjoni pulmonari Effużjoni plewrali Jitnaqqsu l- ħsejjes tan- nifs Disturb respiratorju
Vomiting
Rimettar
Gastrointestinal haemorrhage
emorraġija gastrointestinali
Nausea Diarrhoea
Ulceri fl- ilsien
Ulcerative stomatitis Stomatitis Abdominal pain Dyspepsia Constipation Flatulence
Stomatite Uġigħ addominali
Tongue ulceration Gingivitis Hiccup Eructation Dry mouth
Ġinġivite Sulluzzu
Hepatic function abnormal
Tifwiq Ħalq xott
Pruritus
nfafet
Bullous eruption
Raxx makulo- papulari
Maculo-papular rash
Urtikarja
Urticaria Rash Hyperhidrosis
Raxx eritematuż
Erythematous rash
Disturbi tal- ġilda
Skin disorder
KOMUNI
Musculoskeletal and connective tissue disorders
Disturbi muskolo - skeltrali u tal- connective tissue
Arthralgia Myalgia Skeletal pain Back pain
Artralġja Mijalġja Uġigħ skeltrali Uġigħ fid- dahar
Leg pain Hypertonia
Uġigħ fir- riġlejn Ipertonja
Renal and urinary disorders
Disturbi fil- kliewi u fis - sistema urinarja:
Haematuria Urinary incontinence Urine flow decreased Polyuria Renal function abnormal
Ematurja Inkontinenza urinarja Tnixxija tal- awrina mnaqqsa Poliurja Funzjoni tal- kliewi mhux normali
Chills Fever
Sirdat Deni
Chest pain Influenza-like symptoms
Uġigħ fis- sider Sintomi bħal ta ’ l- influwenza
Pulmonary oedema Peripheral oedema
Edima pulmonarja Edima periferali
Mucositis Oedema mouth Oedema Asthenia Malaise Temperature change sensation Infusion site reaction Pain
Edima Astenja Telqa Sensazzjoni ta ’ bdil fit - temperatura Reazzjoni fil - lok ta ’ l - injezzjoni Uġigħ
Periorbital oedema Mucosal ulceration Infusion site bruising Infusion site dermatitis Infusion site pain
Tbenġil fis- sit ta ’ l- infużjoni Dermatite fis- sit ta ’ l- infużjoni Uġigħ fis- sit ta ’ l- infużjoni
Undesirable Effects Observed During Post-Marketing Surveillance
Effetti Mhux Mixiteqa Osservati Waqt is- Sorveljanza ta ’ Wara t- Tqegħid fis- Suq
Infusion reactions:
Reazzjonijiet għall- infużjoni:
Serious and sometimes fatal reactions, including bronchospasm, hypoxia, syncope, pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, myocardial infarction, arrhythmias, acute cardiac insufficiency and cardiac arrest have been observed.
Kienu osservati reazzjonijiet serji u kultant fatal li jinkludu bronkospażmu, ipoksja, sinkope, infiltrati fil- pulmun, sindrome akuta ta ’ distress respiratorju (ARDS), arrest respiratorju, infart mijokardijaku, arritmiji, insuffiċjenza kardijaka akuta u arrest kardijaku.
Severe anaphylactic and other hypersensitivity reactions, including anaphylactic shock and angioedema, have 10 been reported following MabCampath administration.
Reazzjonijiet anafilattiċi severi u reazzjonijiet ta ’ sensittività eċċessiva oħrajn, li jinkludu xokk anafilattiku u anġjoedima ġew irrapportati wara l- għoti ta 'MabCampath.
These symptoms can be ameliorated or avoided if premedication and dose escalation are utilised (see section 4.4).
Dawn is- sintomi jistgħu jitjiebu jew jiġu evitati jekk tingħata medikazzjoni minn qabel u jkun hemm żjieda gradwali fid- doża (ara sezzjoni 4. 4).
Serious and sometimes fatal viral (e. g. adenovirus, parainfluenza, hepatitis B, progressive multifocal leukoencephalopathy (PML)), bacterial (including tuberculosis and atypical mycobacterioses, nocardiosis), protozoan (e. g. toxoplasma gondii), and fungal (e. g. rhinocerebral mucormycosis) infections, including those due to reactivation of latent infections have occurred during post-marketing surveillance.
Infezzjonijiet serji u xi daqqiet anki fatali kkawżati minn viri (e. ż. adenovirus, parainfluwenza, epatite B, lewkoenċefalopatija multifokali mifruxa (PML)), batterja (inkluż tuberkulożi u mikobatterjosi atipika, nokardjosi), protożoa (e. ż. toxoplasma gondii) u infezzjonijiet ikkawżati minn fungu (e. ż. mukomikosi rinoċerebrali), inkluż dawk dovuti għar - riattivazzjoni ta 'infezzjonijiet rieqda, seħħew waqt sorvelljanza ta ’ wara t- tqegħid fis- suq.
The recommended anti-infective prophylaxis treatment appears to be effective in reducing the risk of PCP and herpes infections (see section 4.4).
Il- kura rakkomandata għal profilassi kontra l- infezzjonijiet tidher li hija effettiva biex tnaqqas ir- riskju t ’ infezzjonijiet ikkawżati minn PCP u herpes (ara sezzjoni 4. 4).
EBV-associated lymphoproliferative disorder has been reported.
Kien irrapportat disturb limfoproliferattiv assoċjat ma 'EBV.
Severe bleeding reactions have been reported.
Kienu rrapportati reazzjonijiet severi ta ’ fsada.
Immune system disorders:
11 Disturbi fis- sistema immuni:
Serious and sometimes fatal autoimmune phenomena including autoimmune haemolytic anaemia, autoimmune thrombocytopenia, aplastic anaemia, Guillain Barré syndrome and its chronic form, chronic inflammatory demyelinating polyradiculoneuropathy have been reported.
Kienu rrappurtati fenomeni awtoimmuni serji u xi kultant fatali inkluż anemija emolitika awtoimmuni, tromboċitopenija autoimmuni, anemija aplastika, is- sindrome ta 'Guillain Barré u l- forma kronika tiegħu, u demyelinating polyradiculoneuropathy infjammatorja kronika.
A positive Coombs test has also been observed.
Kien osservat ukoll riżultat pożittiv għat- test ta 'Coombs.
Fatal Transfusion Associated Graft Versus Host Disease (TAGVHD) has also been reported.
Fatal Transfusion Associated Graft Versus Host Disease (TAGVHD) kienet irrapportata wkoll.
Metabolism and nutritional disorders:
Disturbi fil- metaboliżmu u n- nutrizzjon:
Tumour lysis syndrome with fatal outcome has been reported.
Kienet irrapportata sindrome tad- disintegrazzjoni tat- tumur b’ riżultat fatali.
Intracranial haemorrhage has occurred with fatal outcome, in patients with thrombocytopenia.
Emorraġija intrakranjali seħħet b’ riżultat fatali f’ pazjenti bi tromboċitopenija.
Congestive heart failure, cardiomyopathy, and decreased ejection fraction have been reported in patients previously treated with potentially cardiotoxic agents.
Insuffiċjenza tal- qalb konġestiva, kardjomijopatija, u tnaqqis fil- porzjon mitfugħ ’ l barra kienu rrapportati f’ pazjenti li kienu kkurati qabel b' sustanzi b’ potenzjal kardjotossiku.
Patients have received repeated unit doses of up to 240 mg of MabCampath.
Pazjenti rċevew dożi waħdiena ripetuti sa 240 mg ta 'MabCampath.
The frequency of grade 3 or 4 adverse events, such as fever, hypotension and anaemia, may be higher in these patients.
Il- frekwenza ta ’ avvenimenti avversi ta ’ grad 3 jew 4, bħal deni, pressjoni baxxa u anemija, tista ’ tkun ogħla f’ dawn il- pazjenti.
There is no known specific antidote for MabCampath.
M’ hemm l- ebda antidotu speċifiku magħruf għal MabCampath.
Treatment consists of discontinuation of MabCampath and supportive therapy.
Il- kura tikkonsisti fi twaqqif ta ’ MabCampath u terapija t’ appoġġ.
Pharmacotherapeutic group: monoclonal antibody, ATC code:
Kategorija farmakoterapewtika: antikorp monoklonali, Kodiċi ATC:
Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 21-28 kD lymphocyte cell surface glycoprotein (CD52) expressed primarily on the surface of normal and malignant peripheral blood B and T cell lymphocytes.
Alemtużumab huwa antikorp monoklonali umanizzat tat- tip IgG1 kappa magħmul permezz ta ’ inġinerija ġenetika, speċifiku għal glycoprotein (CD52) fuq il- wiċċ ta ’ ċellula limfoċita tat- tip 21- 28 kD, li jinsab prinċipalment fuq il- wiċċ ta ’ ċelluli limfoċiti B u T periferali tad- demm normali u malinni.
Alemtuzumab was generated by the insertion of six complementarity-determining regions from an IgG2a rat monoclonal antibody into a human IgG1 immunoglobulin molecule.
Alemtużumab kien ġenerat bl- inserzjoni ta ’ sitt reġjuni li jiddeterminaw il- kumplimentarità minn antikorp monoklonali IgG2a tal- firien f’ molekula immunoglobulin IgG1 umana.
Alemtuzumab causes the lysis of lymphocytes by binding to CD52, a highly expressed, non- modulating antigen which is present on the surface of essentially all B and T cell lymphocytes as well as monocytes, thymocytes and macrophages.
Alemtużumab jikkaġuna d- diżintegrazzjoni ta ’ limfoċiti billi jintrabat ma ’ antiġen CD52 li jinsab f’ ammonti kbar u li ma jimmodulax, li essenzjalment jinsab fuq il- wiċċ taċ- ċelluli limfoċiti kollha tat - tip B u T kif ukoll fuq monoċiti, timoċiti u makrofaġi.
The antibody mediates the lysis of lymphocytes via complement fixation and antibody-dependent cell mediated cytotoxicity.
L- antikorp jikkaġuna d- diżintegrazzjoni tal - limfoċiti permezz ta ’ rabta kumplimentari u ċitotossiċità medjata minn ċelluli u dipendenti mill - antikorpi.
The antigen has been found on a small percentage (< 5%) of granulocytes, but not on erythrocytes or platelets.
L- antiġen instab fuq perċentwali żgħir (< 5%) ta ’ granuloċiti, iżda mhux fuq eritroċiti jew plejtlits.
Alemtuzumab does not appear to damage haematopoietic stem cells or progenitor cells.
Alemtużumab ma jidhirx li jikkawża ħsarat lil ċelluli staminali ematopoetiċi jew ċelluli proġenituri.
11 First Line B-CLL Patients The safety and efficacy of MabCampath were evaluated in a Phase 3, open-label, randomized comparative trial of first line (previously untreated) Rai stage I-IV B-CLL patients requiring therapy (Study 4).
Is- sigurtà u l- effikaċja ta ’ MabCampath kienu evalwati fi prova ta ’ Fażi 3, open- label, randomised u komparattiva ta ’ pazjenti b’ B- CLL ta ’ Rai stage I- IV kkurati għall- ewwel darba (mhux ikkurati qabel) li kienu jeħtieġu terapija (Studju 4).
MabCampath was shown to be superior to chlorambucil as measured by the primary endpoint progression free survival (PFS) (see Figure 1).
MabCampath intwera li hu superjuri għal chlorambucil kif imkejjel mill- mira primarja ta ’ sopravivenza mingħajr progressjoni (ara Figura 1).
Progression Free Survival in First Line Study (by Treatment Group)
0. 43, 0. 77
The secondary objectives included complete response (CR) and overall response (CR or partial response) rates using the 1996 NCIWG criteria, the duration of response, time to alternative treatment and safety of the two treatment arms.
L- oġġettivi sekondarji kienu jinkludu rati ta ’ rispons sħiħ (CR) u rati ta ’ risponsi globali (CR jew rispons parzjali) bl- użu tal- kriterji NCIWG ta ’ l- 1996, it- tul tar- rispons, iż- żmien sa kura alternattiva u s- sigurtà taż- żewg gruppi ta ’ kura.
Summary of First-Line Patient Population and Outcomes
Sommarju tal- Popolazzjonijiet ta ’ Pazjenti kkurati għall- Ewwel darba u r- Riżultati
Independent Review of Response Rate and Duration
Analiżi Indipendenti tar- Rata u t- tul tar- Rispons
P value
Valur P
Median Age (Years) Rai Stage III/ IV Disease
Età Medjana (Snin)
Not Applicable Not Applicable
Rispons Sħiħ
Overall Response Rate Complete Response MRD negative****
MRD negattiv ****
83.2% 24.2% 7.4%
59. 1%
55.4% 2.0% 0.0%
53. 4%
< 0.0001* < 0.0001* 0.0008*
Ma Japplikax
Partial Response Duration of Response**, CR or PR (Months)
Tul tar- Rispons **, CR jew PR
Not Applicable Not Applicable
Ma Japplikax
K-M median (95% Confidence Interval)
K- M medjan (95% Intervall ta ’ Kunfidenza)
(11.5, 23.0)
(11. 5, 23. 0)
(10.2, 14.3)
(10. 2, 14. 3)
Time to Alternative Treatment (Months) K-M median (95% Confidence Interval)
(Xhur) K- M medjan (95% Intervall ta ’ Kunfidenza) * Test Pearson chi- square jew test Exact ** It- Tul ta ’ l- aħjar rispons
23.3 (20.7, 31.0)
(20. 7, 31. 0)
14.7 (12.6, 16.8)
(12. 6, 16. 8)
*Pearson chi-square test or Exact test ** Duration of best response *** log-rank test stratified by Rai group (Stage I-II vs III-IV) **** by 4-colour flow
*** Test log- rank stratifikat skond il- grupp Rai (Stadju I- II vs III- IV) **** b’ influss ta ’ 4- kuluri
Cytogenetic Analyses in First Line B-CLL Patients:
13 Analiżi Ċitoġenika għal Pazjenti b’ B- CLL Ikkurati għall- Ewwel Darba:
The cytogenetic profile of B-CLL has been increasingly recognized as providing important prognostic information and may predict response to certain therapies.
Il- profil ċitoġenetiku ta ’ B- CLL qed ikun identifikat dejjem aktar li jagħti informazzjoni prognostika importanti u tista ’ tipprevedi r- rispons ta ’ ċertu terapiji.
Of the first-line patients (n=282) in whom baseline cytogenetic (FISH) data were available in Study 4, chromosomal aberrations were detected in 82%, while normal karyotype was detected in 18%.
Mill- pazjenti kkurati għall- ewwel darba (n=282) li għalihom it- tagħrif ċitoġeniku fil- linja bażi (FISH) kien disponibbli fi Studju 4, aberrazzjonijiet kromosomali ġew osservati fi 82%, filwaqt li karjotip normali kien osservat fi 18%.
Chromosomal aberrations were categorized according to Döhner’ s hierarchical model.
L - aberrazzjonijiet kromosomali kienu mqassma f’ kategoriji skond il- mudell ġerarkiku ta ’ Döhner.
In first line patients, treated with either MabCampath or chlorambucil, there were 21 patients with the 17p deletion, 54 patients with 11q deletion, 34 patients with trisomy 12, 51 patients with normal karyotype and 67 patients with sole 13q deletion.
F’ pazjenti kkurati għall- ewwel darba, b’ MabCampath jew b’ chlorambucil, kien hemm 21 pazjent bi tneħħija ta ’ bis- 17 p, 54 pazjent bi tneħħija ta ’ 11 q, 34 pazjent b’ trisomy 12, 51 pazjent b’ karjotip normali u 67 pazjent bi tneħħija ta ’ 13 q waħedha.
ORR was superior in patients with any 11q deletion (87% v 29%; p < 0.0001) or sole deletion 13q (91% v 62%; p=0.0087) treated with MabCampath compared to chlorambucil.
ORR kien superjuri f’ pazjenti b’ kull tneħħija ta ’ 11q (87% v 29%; p < 0. 0001) jew tneħħija ta ’ 13q waħedha (91% v 62%; p=0. 0087) kkurati b’ MabCampath meta mqabbel ma ’ chlorambucil.
A trend toward improved ORR was observed in patients with 17p deletion treated with MabCampath (64% v 20%; p=0.0805).
Xejra lejn ORR imtejjeb kienet osservata f’ pazjenti bi tneħħija ta ’ 17p ikkurati b’ MabCampath (64% v 20%; p - 0. 0805).
Complete remissions were also superior in patients with sole 13q deletion treated with MabCampath (27% v 0%; p=0.0009).
Irkupru komplut kien ukoll superjuri f’ pazjenti bi tneħħija ta ’ 13q waħedha ikkurati b’ MabCampath (27% v 0%; p=0. 0009).
Median PFS was superior in patients with sole 13q deletion treated with MabCampath (24.4 v 13.0 months; p=0.0170 stratified by Rai Stage).
PFS medjan kien superjuri f’ pazjenti bi tneħħija ta ’ 13 q waħedha kkurati b’ MabCampath (24. 4 v 13. 0 xhur; p=0. 0170 stratifikati skond Stadju Rai).
A trend towards improved PFS was observed in patients with 17p deletion, trisomy 12 and normal karyotype, which did not reach significance due to small sample size.
Xejra lejn PFS imtejjeb kienet osservata f’ pazjenti bi tneħħija ta ’ 17q, trisomy 12 u karjotip normali, li ma laħqitx sinifikanza minħabba daqs ta ’ kampjun żgħir.
Assessment of CMV by PCR:
Analiżi ta ’ CMV permezz ta ’ PCR:
In the randomized controlled trial in first line patients (Study 4), patients in the MabCampath arm were tested weekly for CMV using a PCR (polymerase chain reaction) assay from initiation through completion of therapy, and every 2 weeks for the first 2 months following therapy.
Fil- prova randomised b’ kontrolli f’ pazjenti kkurati għall- ewwel darba (Studju 4), il- pazjenti fil- grupp ta ’ MabCampath kienu ttestjati kull ġimgħa għal CMV permezz ta ’ analiżi ta ’ PCR (polymerase chain reaction) mill- bidu sa tmiem it- terapija, u kull ġimagħtejn għall- ewwel xahrejn wara tmiem it- terapija.
In this study, asymptomatic positive PCR only for CMV was reported in 77/ 147 (52.4%) of MabCampath-treated patients; symptomatic CMV infection was reported less commonly in 23/ 147 MabCampath treated patients (16%).
F’ dan l- istudju, CMV mhux sintomatiku pożittiv biss permezz ta ’ PCR kien irrapportat f’ 77/ 147 (52. 4%) pazjent ikkurat b’ MabCampath; infezzjoni sintomatika ta ’ CMV kienet irrapportata b’ mod inqas komuni f’ 23/ 147 pazjent (16%) ikkurat b’ MabCampath.
In the MabCampath arm 36/ 77 (46.8%) of patients with asymptomatic PCR positive CMV received antiviral therapy and 47/ 77 (61%) of these patients had MabCampath therapy interrupted.
Fil- grupp ta ’ MabCampath 36/ 77 (46. 8) pazjent b’ CMV mhux sintomatiku pożittiv bil- PCR irċevew terapija antivirali u 47/ 77 (61%) minn dawn il- pazjenti kellhom it- terapija ta ’ MabCampath interrota.
The presence of asymptomatic positive PCR for CMV or symptomatic PCR positive CMV infection during treatment with MabCampath had no measurable impact on progression free survival (PFS).
Il- preżenza ta ’ CMV mhux sintomatiku pożittiv permezz tal- PCR jew infezzjoni sintomatika ta ’ CMV pożittiva permezz ta ’ PCR waqt il- kura b’ MabCampath ma kellha l- ebda impatt li jista ’ jitkejjel fuq is- sopravivenza mingħajr progressjoni (PFS).
Previously treated B-CLL Patients:
Pazjenti b’ B- CLL ikkurati qabel:
Determination of the efficacy of MabCampath is based on overall response and survival rates.
Id- determinazzjoni ta 'l- effikaċja ta' MabCampath hija msejsa fuq ir- rispons globali u r- rati ta ’ sopravivenza.
Data available from three uncontrolled B-CLL studies are summarised in the following table:
Dejta disponibbli minn tliet studji dwar B- CLL mingħajr kontrolli huma miġbura fil - qosor fit- tabella li ġejja:
Efficacy Parameters
Kriterji ta ’ l- effikaċja
Study 3
Studju 3
Number of Patients
Numru ta 'Pazjenti
24
24 b’ B- CLL
B-CLL pts who had B-CLL pts who had
Pazjenti b’ B- CLL li Grupp Dijanjostiku
received an alkylating agent and had failed fludarabine
Pazjenti b’ B- LL li kienu rċevew alkylating agent u
failed to respond or relapsed following treatment with conventional chemotherapy
kienu naqsu milli jirrispondu jew
pts who had failed to respond or relapsed following treatment with fludarabine
(flimkien ma ’ PLL) li kienu naqsu milli jirrispondu jew