qanastek/EMEA-V3 huggingface dataset:
System Organ
Sistema tal - Klassifika tal - Organi Infezzjonijiet u
Very
Komuni Ħafna Komuni Mhux Komuni Mhux Magħruf infezzjonijiet sepsi, infezzjoni serja + mill- batterja, pnewmonja, ikkawżata minn
Common
infestazzjonijiet + virus1,
Uncommon
infezzjonijiet
Unknown
infezzjoni bid -
Class
deni, +herpes
Common
mill- virus, +
Infections and
riattivazzjoni ta ’
bacterial
bronkite
sepsis, +
zoster, +infezzjoni fl- apparat respiratorju, infezzjoni mill - moffa, infezzjonijiet b’ etjoloġija mhux magħrufa, + bronkite akuta, + sinusite
serious viral
epatite B1 newtropenija
infestations
Disturbi tad -
infections,
newtropenja,
pneumonia, +
anemija,
infection1,
disturbi fil -
viral
ittardjata2,
febrile infection, +
demm u tas -
hepatitis B
lewkopenja,
infections, + bronchitis
tromboċitopenija,
reactivation1
koagulazzjoni,
Very
+
Uncommon
anemija aplastika,
Unknown
sistema limfatika
Common
newtropenija
Blood and lymphatic system disorders
panċitopenija
coagulation disorders, aplastic anaemia,
anemija
Late neutropenia2, transient increase
żjieda temporanja
pancytopenia neutropenia
bid- deni
haemolytic anaemia, lymphadenopathy
emolitika, limfadenopatija
in serum IgM levels2
fil- livelli ta ’ IgM fis- serum2
Immune system disorders
Disturbi fis - sistema immuni
infusion hypersensitivity related reactions, angioedema
sensittività eċċessiva
tumour lysis syndrome3, cytokine release syndrome3, serum sickness, anaphylaxis
sindrome tal- lisi tat- tumur3,
Metabolism and nutrition disorders
Disturbi fil - metaboliżmu u n - nutrizzjoni Disturbi psikjatriċi
hyperglycaemia, weight decrease, peripheral oedema, face
infużjoni, anġjoedima
oedema, increased LDH, hypocalcaemia Psychiatric disorders
ipergliċemija, tnaqqis fil- piż, edima periferali, edima fil- wiċċ, żjieda fl- LDH, ipokalċimja
depression, nervousness,
depressjoni, nervi,
paraesthesia, hypoaesthesia, agitation, insomnia, vasodilatation, dizziness, anxiety
parestesija, ipoestesija, aġitazzjoni, nuqqas ta ’ rqad, vażodilatazzjoni, sturdament, ansjetà
Dysgeusia
Disġewsja
cranial neuropathy, peripheral neuropathy facial nerve palsy4, loss of other senses4
newropatija kranjali, newropatija periferali, paralisi tan- nerv tal - wiċċ4, telf ta ’ sensi oħra4
Eye disorders
Disturbi fl - għajnejn Disturbi fil - widnejn u fis - sistema labirintika
lacrimation disorder, conjunctivitis
telf sever tal - vista4 telf tas- smigħ4
severe vision loss4
11 Sistema tal - Klassifika tal - Organi
Ear and labyrinth disorders
Komuni Ħafna Komuni
tinnitus, ear pain
Mhux Komuni
hearing loss4
Mhux Magħruf
myocardial infarction3 and 5,
insuffiċjenza
left ventricular failure, + supraventricular
insuffiċjenza tal -
heart failure3 and 5, severe cardiac
mijokardijaku3 u 5,
arrhythmia, +atrial
ventrikulari tax - xellug, +takikardja
tachycardia, +
arritmija, +
events 3 and 5
avvenimenti kardijaċi severi 3 u
fibrillation, tachycardia, + cardiac disorder
fibrillazjoni atrijali, takikardja, +
ventricular tachycardia, +angina, + myocardial ischaemia, bradycardia,
ventrikulari, + anġina, + iskemija mijokardijaka, bradikardja
hypertension, orthostatic hypotension, hypotension
pressjoni għolja,
vasculitis (predominately cutaneous), leukocytoclastic vasculitis
vaskulite (l- biċċa
Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji,
bronchospasm3, respiratory disease, chest pain, dyspnoea, increased cough, rhinitis
pressjoni ortostatika baxxa, pressjoni baxxa bronkospażmu, marda
asthma, bronchiolitis obliterans, lung disorder, hypoxia
ażżma, bronkolite obliterans, disturb fil- pulmun, ipoxja
respiratory failure3, pulmonary infiltrates, interstitial pneumonitis
l- kbira fil- ġilda), vaskulite lewkoċitoklastika insuffiċjenza respiratorja3,
11
toraċiċi u
System Organ
respiratorja, uġigħ
Very
infiltrati fil -
Common
medjastinali
Uncommon
fis- sider, qtugħ ta ’
Unknown
pulmun,
Class
nifs, żjieda fis - sogħla, rinite
Common
pnewmonite ta ’ l - interstizju
nausea
tqalligħ
vomiting, diarrhoea, abdominal pain, dysphagia, stomatitis, constipation, dyspepsia, anorexia, throat irritation
rimettar, dijarea,
abdominal enlargement
tkabbir ta ’ l -
gastro-intestinal perforation6
perforazzjoni gastro- intestinali6
Skin and subcutaneous
intestinali
pruritis, rash, +
Disturbi fil- ġilda
urticaria, sweating, night
urtikarja, għaraq,
severe bullous skin reactions,
Reazzjonijiet bl -
tissue disorders Musculoskeletal, connective tissue and bone disorders
u fit- tessuti ta ’ taħt il- ġilda Disturbi muskolu - skeltrali u tal - connective tissue Disturbi fil- kliewi u fis- sistema urinarja
alopecia
alopeċja
sweats, +skin disorder hypertonia, myalgia, arthralgia, back pain, neck pain, pain
għaraq bil- lejl, + disturbi fil- ġilda ipertonja, mijalġja, artralġja, uġigħ fid- dahar, uġigħ fl- għonq, uġigħ
toxic epidermal necrolysis6
imsiemer severi fil- ġilda, nekrolisi tossika ta ’ l- epidermide6 insuffiċjenza tal - kliewi3
Renal and urinary disorders
Disturbi ġenerali
renal failure3
deni, kesħa,
General disorders and administration
uġigħ fil- post ta ’
fever, chills, asthenia,
u kundizzjonijiet
tumour pain, flushing, malaise, cold syndrome, +
astenja, uġigħ ta ’
pain at the infusion site
fwawar, tħossok
site conditions
l- infużjoni
headache
ta 'mnejn jingħata
fatigue, + shivering, + multi-organ failure3
ma ’ tiflaħx, sindrome ta ’ riħ, + għeja, +tregħid, + insuffiċjenza ta ’ ħafna organi3
Investigations
Komuni Ħafna Komuni
decreased IgG levels
Mhux Magħruf
For each term, the frequency count was based on reactions of all grades (from mild to severe), except for terms marked with "+" where the frequency count was based only on severe (≥ grade 3 NCI common toxicity criteria) reactions.
Investigazzjonijiet livelli mnaqqsa ta ’ IgG Għal kull terminu, l- għadd tal- frekwenza kien ibbażat fuq reazzjonijiet ta ’ kull grad (minn ħfief sa severi), ħlief għat- termini mmarkati b ’ "+" fejn l- għadd tal- frekwenza kien ibbażat biss fuq reazzjonijiet severi (kriterji komuni tat- tossiċità ta ’ NCI ≥ grad 3).
Only the highest frequency observed in the trials is reported 1 see also section infection below 2 see also section haematologic adverse reactions below 3 see also section infusion-related reactions below.
1 ara wkoll is- sezzjoni infezzjoni taħt 2 ara wkoll is- sezzjoni reazzjonijiet ematoloġiċi avversi taħt 3 ara wkoll is- sezzjoni reazzjonijiet relatati ma ’ l- infużjoni taħt.
Rarely fatal cases reported 4 signs and symptoms of cranial neuropathy.
Każijiet fatali rrapportati b’ mod rari 4 sinjali u sintomi ta ’ newtropatija kranjali.
Occurred at various times up to several months after completion of MabThera therapy 5 observed mainly in patients with prior cardiac condition and/ or cardiotoxic chemotherapy and were mostly associated with infusion-related reactions 6 includes fatal cases
Seħħew fi żminijiet differenti sa diversi xhur wara t- tmiem tat - terapija b’ MabThera 5 osservati l- aktar f’ pazjenti b’ kundizzjoni tal- qalb minn qabel u/ jew kimoterapija kardjotossika u kienu assoċjati l- aktar ma ’ reazzjonijiet relati ma ’ l- infużjoni 6 inkluż każijiet fatali
The following terms have been reported as adverse events during clinical trials, however, were reported at a similar or lower incidence in the MabThera-arms compared to control arms: haematotoxicity, neutropenic infection, urinary tract infection, sensory disturbance, pyrexia.
Ematotossiċità, infezzjoni newtropenika, infezzjoni fl- apparat urinarju, disturb sensorjali, deni.
Infusion-related reactions Signs and symptoms suggestive of an infusion-related reaction were reported in more than 50% of patients in clinical trials, and were predominantly seen during the first infusion, usually in the first one to two hours.
Reazzjonijiet relatati ma ’ l- infużjoni Sinjali u sintomi li jissuġġerixxu reazzjoni relatata ma ’ l- infużjoni kienu rrapportati f’ aktar minn 50% tal- pazjenti fi provi kliniċi, u fil- biċċa l- kbira dehru waqt l- ewwel infużjoni, normalment fl- ewwel siegħa jew sagħtejn.
These symptoms mainly comprised fever, chills and rigors.
Dawn is- sintomi prinċipalment kienu deni, kesħa u tertir.
Other symptoms included flushing, angioedema, bronchospasm, vomiting, nausea, urticaria/ rash, fatigue, headache, throat irritation, rhinitis, pruritus, pain, tachycardia, hypertension, hypotension, dyspnoea, dyspepsia, asthenia and features of tumor lysis syndrome.
Sintomi oħra inkludew fwawar, angjoedima, bronkospażmu, rimettar, tqalligħ, urtikarja/ raxx, għeja, uġigħ ta ’ ras, irritazzjoni fil- griżmejn, rinite, ħakk, uġigħ, takikardja, pressjoni għolja, pressjoni baxxa, qtugħ ta ’ nifs, dispepsja, astenja u karatteristiċi tas- sindrome tal- lisi tat- tumur.
Severe infusion-related reactions (such as bronchospasm, hypotension) occurred in about 10% of the cases.
Reazzjonijiet severi relatati ma ’ l- infużjoni (bħal bronkospażmu, pressjoni baxxa) seħħew f’ madwar 10% tal- każijiet.
Additional reactions reported in some cases were myocardial infarction, atrial fibrillation and pulmonary oedema.
Reazzjonijiet oħra rrapportati f’ xi każijiet kienu infart mijokardijaku, fibrillazzjoni atrijali u edima pulmonari.
12 events (heart failure, myocardial infarction, atrial fibrillation), pulmonary oedema, multi-organ failure, tumour lysis syndrome, cytokine release syndrome, renal failure, and respiratory failure were reported at lower or unknown frequencies.
Rkadar ta ’ kundizzjonijiet kardijaċi eżistenti minn qabel bħal anġina pectoris jew insuffiċjenza tal- qalb konġestiva jew avvenimenti kardijaċi severi (insuffiċjenza tal- qalb, infart mijokardijaku, fibrillazzjoni atrijali), edima pulmonari, insuffiċjenza ta ’ ħafna organi, sindrome tal- lisi tat- tumur, sindrome tar- reħa ta ’ cytokine, insuffiċjenza tal- kliewi, u insuffiċjenza respiratorja kienu rrapportati bi frekwenza aktar baxxa jew bi frekwenza mhux magħrufa.
The incidence of infusion-related symptoms decreased substantially with subsequent infusions and is < 1% of patients by the eighth cycle of MabThera(-containing) treatment.
L- inċidenza ta ’ sintomi relatati ma ’ l- infużjoni naqset b’ mod sostanzjali b’ infuzjonijiet sussegwenti u hija < 1% tal- pazjenti mat- tmin ċiklu ta ’ kura b ’ (li fiha) MabThera.
Infections MabThera induces B-cell depletion in about 70-80% of patients, but was associated with decreased serum immunoglobulins only in a minority of patients.
Infezzjonijiet MabThera jikkaġuna tnaqqis taċ- ċellula B f’ madwar 70- 80% tal- pazjenti, iżda kien assoċjat ma ’ tnaqqis fl- immunoglobulins fis- serum f' minoranza ta ’ pazjenti.
Localized candida infections as well as Herpes zoster was reported at a higher incidence in the MabThera-containing arm of randomized studies.
Infezzjonijiet lokalizzati ta ’ candida kif ukoll Herpes zoster kienu rrapportati f’ inċidenza ogħla fil - grupp ta ’ l- istudji randomized li kien fih MabThera.
Severe infections were reported in about 4% of patients.
Infezzjonijiet severi kienu rrapportati f' madwar 4% tal- pazjenti.
Higher frequencies of infections overall, including grade 3 or 4 infections, were observed during MabThera maintenance treatment up to 2 years when compared to observation. There was no cumulative toxicity in terms of infections reported over a 2-year treatment period.
Ma kienx hemm tossiċità kumulattiva f’ termini ta ’ infezzjonijiet irrapportata fuq perijodu ta ’ kura ta ’ sentejn.
In addition, other serious viral infections either new, reactivated or exacerbated, some of which were fatal, have been reported with MabThera treatment.
Barra dan, infezzjonijiet virali serji oħra, ġodda, attivazzjoni mill- ġdid jew irkadar, li wħud minnhom kienu fatali, ġew irrapportati b’ kura b’ MabThera.
The majority of patients had received MabThera in combination with chemotherapy or as part of a hematopoetic stem cell transplant.
Il- maġġoranza ta ’ pazjenti kienu rċevew MabThera flimkien ma ’ kimoterapija jew bħala parti minn trapjant ematopoetiku ta ’ ċelluli staminali.
Examples of these serious viral infections are infections caused by the herpes viruses (Cytomegalovirus, Varicella Zoster Virus and Herpes Simplex Virus), JC virus (progressive multifocal leukoencephalopathy (PML)) and hepatitis C virus.
Eżempji ta ’ dawn l- infezzjonijiet virali serji huma infezzjonijiet ikkawżati mill- virusis ta ’ l- herpes (Cytomegalovirus, Virus tal- Varicella Zoster u Virus ta ’ l- Herpes Simplex), virus JC (lewkoenċefalopatija multifokali progressiva (PML)) u virus ta ’ l- epatite Ċ.
Cases of hepatitis B reactivation, have been reported, the majority of which were in subjects receiving MabThera in combination with cytotoxic chemotherapy.
Kienu rrapportati każijiet ta 'riattivazzjoni ta' l- epatite B, li l- maġġoranza tagħhom seħħew f’ individwi li rċevew MabThera flimkien ma ’ kimoterapija ċitotossika.
Progression of Kaposi’ s sarcoma has been observed in rituximab-exposed patients with pre-existing Kaposi’ s sarcoma.
Progressjoni tas- sarkoma ta ’ Kaposi kienet osservata f’ pazjenti esposti għal rituximab b’ sarkoma ta ’ Kaposi eżistenti minn qabel.
These cases occurred in non-approved indications and the majority of patients were HIV positive.
Dawn il- każijiet seħħew f’ indikazzjonijiet mhux approvati u l- maġġoranza tal- pazjenti kienu pożittivi għall- HIV.
Haematologic Adverse Reactions In clinical trials with MabThera monotherapy given for 4 weeks, haematological abnormalities occurred in a minority of patients and were usually mild and reversible.
13 Reazzjonijiet Ematoloġiċi Avversi Fi provi kliniċi b’ monoterapija b’ MabThera mogħtija għal 4 ġimgħat, anormalitajiet ematoloġiċi seħħew f’ minoranza ta ’ pazjenti u normalment kienu ħfief u riversibbli.
Severe (grade 3/ 4) neutropenia was reported in 4.2%, anaemia in 1.1% and thrombocytopenia in 1.7% of the patients.
Newtropenija severa (grad 3/ 4) kienet irrapportata f’ 4. 2%, anemija f’ 1. 1% u tromboċitopenija f’ 1. 7% tal- pazjenti.
4%, grade 3/ 4) were reported at a higher incidence when compared to observation.
Waqt kura ta ’ manteniment b’ MabThera sa sentejn, lewkopenija (5% vs 2%, grad 3/ 4) u newtropenija (10% vs 4%, grad 3/ 4) kienu rrapportati f’ inċidenza ogħla meta mqabbel ma ’ l- osservazzjoni.
The incidence of thrombocytopenia was low (< 1, grade 3/ 4%) and was not different between treatment arms.
L- inċidenza ta ’ tromboċitopenija kienet baxxa (< 1, grad 3/ 4%) u ma kienetx differenti bejn il- gruppi ta ’ kura.
CHOP 88%, R-FC 30% vs.
Fi studji b’ MabThera flimkien ma ’ kimoterapija, lewkopenija ta ’ grad 3/ 4 (R- CHOP 88% vs CHOP 79%, R- FC 23% vs FC 12%), newtropenija (R- CVP 24% vs CVP 14%; R- CHOP 97% vs CHOP 88%, R- FC 30% vs.
FC 1%) were reported higher frequencies when compared to chemotherapy alone.
FC 19%), panċitopenija (R- FC 3% vs FC 1%) kienu rrapportati bi frekwenza ogħla meta mqabbel ma ’ kimoterapija waħedha.
However, the higher incidence of neutropenia in patients treated with MabThera and chemotherapy was not associated with a higher incidence of infections and infestations compared to patients treated with chemotherapy alone and the neutropenia was not prolonged in the MabThera group.
Madankollu, l- inċidenza ogħla ta ’ newtropenija f’ pazjenti kkurati b’ MabThera u kimoterapija ma kientx assoċjata ma ’ inċidenza ogħla ta ’ infezzjonijiet u infestazzjonijiet meta mqabbel ma ’ pazjenti kkurati b’ kimoterapija waħedha u n- newtropenija ma kienetx imtawwla fil- grupp b’ MabThera.
There were no differences reported for the incidence of thrombocytopenia or anaemia.
Ma kienx hemm differenzi rrapportati għall- inċidenza ta ’ tromboċitopenija jew anemija.
Some cases of late neutropenia occurring more than four weeks after the last infusion of MabThera were reported.
Kienu rrapportati xi każijiet ta ’ newtropenija ttardjata li seħħew aktar minn erba ’ ġimgħat wara l- aħħar infużjoni ta ’ MabThera.
FC 71%).
FL- istudju primarju dwar CCL, pazjent fl - istadju Binet Ċ kellhom aktar avvenimenti avversi fil- grupp R- FC meta mqabbel mal- grupp FC (R- FC 83% vs FC 71%).
In studies of MabThera in patients with Waldenstrom’ s macroglobulinaemia, transient increases in serum IgM levels have been observed following treatment initiation, which may be associated with hyperviscosity and related symptoms.
Fi studji dwar MabThera f’ pazjenti b’ makroglobulinimja ta ’ Waldenstrom, ġew osservati żjidiet temporanji fil- livelli ta ’ IgM fis- serum wara l- bidu tal- kura, li jistgħu jkunu assoċjati ma ’ viskożità eċċessiva u sintomi relatati.
The transient IgM increase usually returned to at least baseline level within 4 months.
Iż- żjieda temporanja fl- IgM ġeneralment irritornat għal- livell fil- linja bażi fi żmien 4 xhur.
Cardiovascular reactions Cardiovascular reactions during clinical trials with MabThera monotherapy were reported in 18.8% of patients with the most frequently reported events being hypotension and hypertension.
Reazzjonijiet kardjovaskulari Waqt il- provi kliniċi b’ monoterapija b’ MabThera, reazzjonijet kardjovaskulari Kienu rrapportati fi 18. 8% tal- pazjenti u l- aktar avvenimenti rrapportati b’ mod frekwenti kienu pressjoni baxxa u pressjoni għolja.
Cases of grade 3 or 4 arrhythmia (including ventricular and supraventricular tachycardia) and angina pectoris during infusion were reported.
Kienu rrapportati każijiet ta ’ arritmija ta ’ grad 3 jew 4 (inkluż takikardija ventrikulari u supraventrikulari) u anġina pectoris waqt l- infużjoni.
During maintenance treatment, the incidence of grade 3/ 4 cardiac disorders was comparable between patients treated with MabThera and observation.
Waqt kura ta ’ manteniment, l- inċidenza ta ’ disturbi kardijaċi ta ’ grad 3/ 4 kienet komparabbli bejn pazjenti kkurati b’ MabThera u l- osservazzjoni.
In studies evaluating MabThera in combination with chemotherapy, the incidence of
Avvenimenti kardijaċi kienu rrapportati bħala avvenimenti avversi severi (inkluż fibrillazzjoni atrijali, infart mijokardijaku, insuffiċjenza ventrikolari tax- xellug, iskemija mijokardijaka) f’ 3% tal- pazjenti kkurati b’ MabThera meta mqabbel ma ’ < 1% fuq osservazzjoni.
13 grade 3 and 4 cardiac arrhythmias, predominantly supraventricular arrhythmias such as tachycardia and atrial flutter/ fibrillation, was higher in the R-CHOP group (14 patients, 6.9%) as compared to the CHOP group (3 patients, 1.5%).
Fi studji li vvalutaw MabThera flimkien ma ’ kimoterapija, l- inċidenza ta ’ arritmija kardijaka ta ’ grad 3 u 4, l- aktar arritmija supraventrikolari bħal takikardija u taħbit irregolari/ fibrillazzjoni atrijali, kienet ogħla fil- grupp ta ’ R - CHOP (14- il pazjent, 6. 9%) meta mqabbel mal- grupp ta ’ CHOP (3 pazjenti, 1. 5%).
All of these arrhythmias either occurred in the context of a MabThera infusion or were associated with predisposing conditions such as fever, infection, acute myocardial infarction or pre-existing respiratory and cardiovascular disease.
Dawn l- arritmiji kollha seħħew fil- kuntest ta ’ infużjoni ta ’ MabThera jew kienu assoċjati ma ’ kudizzjonijiet li jippredisponu bħal deni, infezzjoni, infart mijokardijaku akut jew mard respiratorju u kardjovaskulari eżistenti minn qabel.
No difference between the R-CHOP and CHOP group was observed in the incidence of other grade 3 and 4 cardiac events including heart failure, myocardial disease and manifestations of coronary artery disease.
Ma kienet osservata l- ebda differenza bejn il- grupp ta ’ R- CHOP u CHOP fl - inċidenza ta ’ avvenimenti kardijaċi oħra ta ’ grad 3 u 4 inkluż insuffiċjenza tal- qalb, mard mijokardijaku u manifestazzjonijiet tal- marda ta ’ l- arterji koronarji.
In the CLL first-line study, the overall incidence of grade 3 or 4 cardiac disorders was low (4% R-FC, 3% FC).
Fl- istudju primarju dwar CCL, l - inċidenza globali ta ’ disturbi tal- qalb ta ’ grad 3 jew 4 kien baxx (4% R- FC, 3% FC).
Neurologic events During the treatment period, four patients (2%) treated with R-CHOP, all with cardiovascular risk factors, experienced thromboembolic cerebrovascular accidents during the first treatment cycle.
Avvenimenti newroloġiċi Waqt il- perijodu ta ’ kura, erba ’ pazjenti (2%) ikkurati b’ R- CHOP, kollha b’ fatturi ta ’ riskju kardjovaskulari, kellhom esperjenza ta ’ inċidenti ċerebrovaskulari tromboembolitiċi waqt l- ewwel ċiklu ta ’ kura.
There was no difference between the treatment groups in the incidence of other thromboembolic events.
Ma kien hemm l- ebda differenza bejn il- gruppi ta ’ kura fl- inċidenza ta ’ avvenimenti tromboembolitiċi oħra.
In contrast, three patients (1.5%) had cerebrovascular events in the CHOP group, all of which occurred during the follow-up period.
B’ kuntrast, tliet pazjenti (1. 5%) fil- grupp ta ’ CHOP kellhom avvenimenti ċerebrovaskulari li lkoll seħħew waqt il- perijodu ta ’ wara.
In the CLL first-line study, the overall incidence of grade 3 or 4 nervous system disorders was low (4% R-FC, 4% FC).
Fl- istudju primarju dwar CCL, l- inċidenza globali ta ’ disturbi fis- sitema nervuża ta ’ grad 3 jew 4 kien baxx (4% R- FC, 4% FC).
Gastrointestinal Disorders Gastrointestinal perforation in some cases leading to death has been observed in patients receiving MabThera for treatment of non Hodgkin lymphoma.
Disturbi Gastro- intestinali Perforazzjoni gastro- intestinali li f’ xi każijiet wasslet għall- mewt kienet osservata f’ pazjenti li rċevew MabThera għall- kura ta ’ limfoma mhux ta ’ Hodgkin.
In the majority of these cases, MabThera was administered with chemotherapy.
Fil- maġġoranza ta ’ dawn il- każijiet, MabThera ingħata flimkien ma ’ kimoterapija.
IgG levels In the clinical trial evaluating MabThera maintenance treatment, median IgG levels were below the lower limit of normal (LLN) (< 7 g/ L) after induction treatment in both the observation and the MabThera groups.
14 Fil- prova klinika li vvalutat kura ta ’ manteniment b’ MabThera, livelli medjana ta ’ IgG kienu taħt il - limitu l- baxx tan- normal (LLN) (< 7 g/ L) wara l- kura ta ’ induzzjoni kemm fil- grupp ta ’ osservazzjoni kif ukoll f’ dak ta ’ MabThera.
In the observation group, the median IgG level subsequently increased to above the LLN, but remained constant in the MabThera group.
Fil- grupp ta ’ osservazzjoni, il- livell medjan ta ’ IgG sussegwentement żdied sa ’ l fuq mil- LLN, iżda baqa ’ kostanti fil- grupp ta ’ MabThera.
The proportion of patients with IgG levels below the LLN was about 60% in the MabThera group throughout the 2 year treatment period, while it decreased in the observation group (36% after 2 years).
Il- proporzjon ta ’ pazjenti b’ livelli ta ’ IgG taħt l- LLN kien madwar 60% fil- grupp ta ’ MabThera tul il- perijodu ta ’ kura ta ’ sentejn, filwaqt li naqas fil- grupp ta ’ osservazzjoni (36% wara sentejn).
Patient subpopulations (MabThera monotherapy) Elderly patients(≥ 65 years):
Sottopopolazzjonijiet ta ’ pazjenti (monoterapija ta ’ MabThera) Pazjenti anzjani (≥ 65 sena):
The incidence of ADRs of all grades and grade 3 / 4 ADR was similar in elderly patients compared to younger patients (< 65 years).
L- inċidenza ta ’ ADRs ta ’ kull grad u ta ’ ADRs ta ’ grad 3/ 4 kienu simili f’ pazjenti anzjani meta mqabbel ma ’ pazjenti iżgħar (< 65 sena).
Bulky disease There was a higher incidence of grade 3/ 4 ADRs in patients with bulky disease than in patients without bulky disease (25.6% vs.
Bulky disease Kien hemm inċidenza ogħla ta ’ ADRs ta ’ grad 3/ 4 f’ pazjenti b’ bulky disease meta mqabbel ma ’ pazjenti mingħajr bulky disease (25. 6% vs 15. 4%).
The incidence of ADRs of any grade was similar in these two groups.
L- inċidenz ta ’ ADRs ta ’ kull grad kienet simili f’ dawn iż- żewġ gruppi.
Re-treatment The percentage of patients reporting ADRs upon re-treatment with further courses of MabThera was similar to the percentage of patients reporting ADRs upon initial exposure (any grade and grade 3/ 4 ADRs).
Kura mill- ġdid Il- perċentwal ta ’ pazjenti li rrapportaw ADRs wara kura mill- ġdid b’ aktar korsijiet ta ’ MabThera kien simili għall- perċentwal ta ’ pazjenti li rrapportaw ADRs wara li kienu esposti fil- bidu (kwalunkwe grad u ADRs ta ’ grad 3/ 4).
Experience from rheumatoid arthritis
Esperjenza minn artrite rewmatika
The overall safety profile of MabThera in rheumatoid arthritis is based on data from patients from clinical trials and from post-marketing surveillance.
Il- profil ta ’ sigurtà globali ta ’ MabThera f’ artrite rewmatika huwa bbażat fuq tagħrif minn pazjenti minn provi kliniċi u minn sorveljanza ta ’ wara t- tqegħid fis- suq.
The clinical efficacy of MabThera, given together with methotrexate was studied in three double blind controlled clinical trials (one phase III two phase II trials) in patients with rheumatoid arthritis.
L- effikaċja klinika ta ’ MabThera, mogħti flimkien ma ’ methotrexate ġiet studjata fi tliet provi kkontrollati tat- tip double blind (prova ta ’ fażi II żewġ provi ta ’ fażi III) f’ pazjenti b’ artrite rewmatika.
More than 1000 patients received at least one treatment course and were followed for periods ranging from 6 months to over 3 years; nearly 600 patients received two or more courses of treatment during the follow up period.
Aktar minn 1000 pazjent irċevew mill- anqas kors wieħed ta ’ kura u kienu segwiti għal perjodi li varjaw minn 6 xhur għal aktar minn 3 snin; kważi 600 pazjent irċevew żewġ korsijiet jew aktar ta ’ kura matul il- perjodu ta ’ wara.
14 Patients received 2 x 1000 mg of MabThera separated by an interval of two weeks; in addition to methotrexate (10-25 mg/ week).
Il- pazjenti rċevew 2 x 1000 mg ta ’ MabThera separati b’ intervall ta ’ ġimagħtejn; flimkien ma ’ methotrexate (10- 25 mg/ ġimgħa).
MabThera infusions were administered after an intravenous infusion of 100 mg methylprednisolone; patients also received treatment with oral prednisone for 15 days.
L- infużjonijiet ta ’ MabThera ngħataw wara infużjoni fil- vini ta ’ 100 mg methylprednisolone; il- pazjenti rċevew ukoll kura bi prednisone orali għal 15- il jum.
ADRs, which occurred with at least a 2% difference compared to the control arm and more frequently by patients who had received at least one infusion of MabThera than among patients that had received placebo in the phase III trial and the combined population included in phase II studies, are listed in the Table below.
L- ADRs, li seħħew b’ differenza ta ’ l- inqas 2% meta mqabbel mal- grupp ta ’ kontroll u aktar ta ’ spiss minn pazjenti li kienu rċevew mill- anqas infużjoni waħda ta ’ MabThera milli fost il- pazjenti li kienu rċevew plaċebo fil- prova ta ’ fażi III u l- popolazzjoni kombinata inkluża fl- istudji ta ’ fażi II, huma elenkati fit - Tabella taħt.
Frequencies are defined as very common (≥ 1/ 10) and common (≥ 1/ 100 to < 1/ 10).
Il- frekwenzi huma definiti bħala komuni ħafna (≥1/ 10) u komuni (≥1/ 100 sa < 1/ 10).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness
L - effetti li huma l- aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk anqas serji.
The most frequent adverse reactions considered due to receipt of 2x1000 mg MabThera in Phase II and III studies were acute infusion reactions.
L- aktar reazzjonijiet avversi frekwenti kkunsidrati bħala dovuti għar- riċeviment ta ’ 2 x 1000 mg ta ’ MabThera fi studji ta ’ Fażi II u III kienu reazzjonijiet akuti għall- infużjoni.
Infusion reactions occurred in 15% patients following the first infusion of rituximab and 5% in placebo patients.
Reazzjonijiet għall - infużjoni seħħew fi 15% tal- pazjenti wara l- ewwel infużjoni ta ’ rituximab u f’ 5% tal- pazjenti fuq plaċebo.
Infusion reactions decreased to 2% following the second infusion in both rituximab and placebo groups.
Ir- reazzjonijiet għall- infużjoni naqsu għal 2% wara t- tieni infużjoni kemm fil- grupp ta ’ rituximab kif ukoll fil- grupp tal- plaċebo.
The safety information collected during post marketing experience reflects the expected adverse reaction profile as seen in clinical trials for MabThera (see section 4.4).
It- tagħrif dwar is- sigurtà miġbur waqt l- esperjenza ta ’ wara t - tqegħid fis- suq jirrifletti l- profil ta ’ reazzjonijiet avversi mistenni kif deher fi provi kliniċi għal MabThera (ara sezzjoni 4. 4).
Table 2
15 Tabella 2
Summary of Adverse Drug Reactions Reported in Clinical Trials or During Postmarketing Surveillance Occurring in Patients with Rheumatoid Arthritis receiving MabThera
Sommarju ta ’ Reazzjonijiet Avversi tal- Mediċina Rrapportati fi Provi Kliniċi jew Waqt Sorveljanza ta ’ Wara t- Tqegħid fis- Suq li Seħħew f’ Pazjenti b’ Artrite Rewmatika li kienu qed jirċievu MabThera
System Organ Infections and Infestations
Sistema tal- Klassifika ta ’ l- Organi
Class Very Common Common any infection, upper urinary tract respiratory tract infections infection
Komuni Ħafna Komuni
Immune System Disorders General disorders and administration site conditions
Infezzjonijiet u
Metabolism and Nutritional Disorders
kull infezzjoni,
hypercholesterolemia
infezzjonijiet fl -
Nervous System disorders Gastrointestinal Disorders
infestazzjonijiet Disturbi fis- Sistema Immuni Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Disturbi fil - metaboliżmu u n - nutrizzjoni Disturbi fis- sistema nervuża Disturbi Gastro - intestinali Disturbi muskolu - skeltrali
Paraesthesia, migraine dyspepsia
infezzjoni fl- apparat respiratorju ta ’ fuq * Reazzjonijiet relatati ma ’ l - infużjoni (tqalligħ, sirdat, rinite, urtikarja u fwawar) pressjoni għolja, raxx, deni, ħakk, irritazzjoni fil - griżmejn u pressjoni baxxa)
Musculo skeletal disorders
apparat urinarju iperkolesterolimja Parasteżija, emigranja dispepsja artralġja / uġigħ muskolu- skeletrali, osteoartrite
arthralgia / musculoskeletal pain, osteoarthritis
* Reazzjonijiet relatati ma ’ l- infużjoni (edima ġeneralizzata, bronkospażmu, tħarħir, edima fil- larinġi, edima anġjonewrotika, ħakk ġeneralizzat, anafilassi, reazzjoni anafilattojda)
*Reactions occurring during or within 24 hours of infusion.
* Reazzjonijiet li jseħħu waqt jew sa 24 siegħa wara l- infużjoni.
See also infusion-related reactions below.
Ara wkoll reazzjonijiet relatati ma ’ l- infużjoni taħt.
Infusion related reactions may occur as a result of hypersensitivity and/ or to the mechanism of action.
Reazzjonijiet relatati ma ’ l- infużjoni jistgħu jseħħu wkoll bħala riżultat ta ’ sensittività eċċessiva u/ jew għall- mekkaniżmu ta ’ azzjoni.
The following terms have been reported as adverse events during clinical trials, however, were reported at a similar incidence in the MabThera-arms compared to control arms: lower respiratory tract infections/ pneumonia, abdominal pain upper, muscle spasms and asthenia.
It- termini li ġejjin ġew irrapportati bħala avvenimenti avversi waqt provi kliniċi, iżda fil- gruppi b’ MabThera kienu rrapportati f’ inċidenza simili meta mqabbla mal- gruppi ta ’ kontroll: infezzjonijiet fl- apparat respiratorju ta ’ taħt/ pnewmonja, uġigħ fl- addome ta ’ fuq, spażmi fil- muskoli u astenja.
Multiple Courses The limited clinical trial data on multiple courses of treatment of RA patients seem to be associated with a similar ADR profile to that observed following first exposure.
Korsijiet multipli L- informazzjoni limitata tal- provi kliniċi dwar korsijiet multipli ta ’ kura ta ’ pazjenti RA donnha li hija assoċjata ma ’ profil simili ta ’ ADR għal dak osservat wara l- ewwel esponiment.
However, worsening of infusion or allergic reactions and failure to B cell deplete following rituximab cannot be excluded in HACA positive patients after repeated exposure to rituximab on the basis of available data.
Madankollu, it- taħżin tar- reazzjonijiet għall- infużjoni jew allerġiċi u l- falliment li titnaqqas iċ- ċellula B wara rituximab ma jistgħux ikunu esklużi f’ pazjenti HACA pożittivi wara esponiment ripetut għal rituximab fuq il- bażi ta ’ l- informazzjoni disponibbli.
The incidence of acute infusion reactions following subsequent treatment courses was generally lower than the incidence following the first infusion of MabThera.
L- inċidenza tar- reazzjonijiet akuti għall- infużjoni wara korsijiet suċċessivi ta ’ kura kienet ġeneralment aktar baxxa mill- inċidenza wara l- ewwel infużjoni ta ’ MabThera.
15 Infusion-related reactions Symptoms suggesting an acute infusion reaction (e. g. pruritis, fever, urticaria/ rash, chills, pyrexia, rigors, sneezing, angioneurotic edema, throat irritation, cough and bronchospasm, with or without associated hypotension or hypertension) were observed in 79/ 540 (15%) patients following their first exposure to MabThera; In a study comparing the effect of glucocorticoid regimen, these events were observed in 5/ 149 (3%) of patients following their first rituximab placebo infusion and 42/ 192 (22%) of patients receiving their first infusion of 1000 mg rituximab.
Reazzjonijiet relatati ma ’ l- infużjoni Sintomi li jissuġġerixxu reazzjoni akuta għall- infużjoni (eż. ħakk, deni, urtikarja/ raxx, kesħa, deni, tregħid, għatis, edima anġjonewrotika, irritazzjoni fil- griżmejn, sogħla u bronkospażmi, bi jew mingħajr pressjoni baxxa jew pressjoni għolja assoċjata) kienu osservati f’ 79/ 540 (15%) pazjent wara l- ewwel esponiment tagħhom għal MabThera; Fi studju li qabbel l- effett ta ’ reġim bil- glukokortikojd, dawn l- episodji kienu osservati f’ 5/ 149 (3%) pazjent wara l- ewwel infużjoni tagħhom ta ’ rituximab plaċebo u fi 42/ 192 (22%) pazjent li rċevew l- ewwel infużjoni tagħhom ta ’ 1000 mg rituximab.
Premedication with intravenous glucocorticoid significantly reduced the incidence and severity of these events.
Premedikazzjoni bi glukokortikojd fil- vini naqqset b’ mod sinifikanti l- inċidenza u s- severità ta ’ dawn l- episodji.
Of the patients who received 1000 mg rituximab without premedication with glucocorticoids, 18/ 65 (28%) experienced an acute infusion reaction, compared with 24/ 127 (19%) in patients given intravenous glucocorticoid premedication, respectively.
16 18/ 65 (28%) esperjenzaw reazzjoni akuta għall- infużjoni, meta mqabbel ma ’ 24/ 127 (19%) f’ pazjenti mogħtija premedikazzjoni bi glukokortikojdi fil- vini, rispettivament.
Infections The rate of infection was approximately 0.9 per patient year in MabThera treated patients.
Infezzjonijiet Ir- rata ta ’ infezzjoni kienet bejn wieħed u ieħor 0. 9 għal kull sena ta ’ pazjent fil- pazjenti ttrattati b’ MabThera.
The infections consisted mostly of upper respiratory tract infections and urinary tract infections.
L- infezzjonijiet kienu jikkonsistu prinċipalment minn infezzjonijiet ta ’ l- apparat respiratorju ta ’ fuq u infezzjonijiet ta ’ l- apparat urinarju.
The incidence of clinically significant infection, some of which were fatal, was 0.05 per patient year in MabThera treated patients.
L- inċidenza ta ’ infezzjonijiet klinikament sinifikanti, li xi wħud minnhom kienu fatali, kienet 0. 05 għal kull sena ta ’ pazjent fil- pazjenti ttrattati b’ MabThera.
Cases of Progressive Multifocal Leukoencephalopathy with fatal outcome have been reported following use of MabThera for the treatment of autoimmune diseases.
Wara l- użu ta ’ MabThera għall- kura ta ’ mard awtoimmuni kienu rrapportati każijiet ta ’ Lewkoenċefalopatija Multifokali Progressiva (PML) b’ riżultat fatali.
This includes Rheumatoid Arthritis and off-label autoimmune diseases, including Systemic Lupus Erythematosus (SLE) and Vasculitis.
Dan jinkludi Artrite Rewmatika u mard awtoimmuni off- label ieħor, inkluż Lupus Eritematosus Sistemika (SLE) u Vaskulite.
All the reported cases had multiple risk factors for PML, including either the underlying disease and or long-term immunosuppressive therapy or chemotherapy.
Il - każijiet irrapportati kollha kellhom diversi fatturi ta ’ riskju għal PML, inkluż l- marda li hemm preżenti u/ jew terapija immunosoppressiva fit- tul jew kimoterapija.
Malignancies The clinical data, particularly the number of repeated courses, are too limited to assess the potential incidence of malignancies following exposure to rituximab, although present data do not seem to suggest any increased risk.
Tumuri malinni L- informazzjoni klinika, b’ mod partikulari n- numru ta ’ korsijiet ripetuti, hija limitata wisq biex tkun evalwata l- inċidenza possibbli ta ’ tumuri malinni wara esponiment għal rituximab, għalkemm l - informazzjoni preżenti ma tissuġġerix xi riskju akbar.
Long-term safety evaluations are ongoing.
L- evalwazzjonijiet tas- sigurtà fuq perijodu fit - tul għadhom għaddejjin.
Cardiovascular Cardiac events were observed in 11% patients in clinical studies with MabThera.
Kardjovaskulari Episodji kardijaċi kienu osservati fi 11% tal- pazjenti fl- istudji kliniċi b’ MabThera.
In placebo controlled studies, serious cardiac events were reported equally in MabThera and placebo treated patients (2%).
Fl- istudji kkontrollati bil- plaċebo, episodji kardijaċi serji ġew irrapportati b’ mod ugwali fil- pazjenti ttrattati b’ MabThera u dawk ittrattati bil- plaċebo (2%).
There has been no experience of overdose in human clinical trials.
Ma kien hemm l- ebda esperjenza ta ’ doża eċċessiva fil- provi kliniċi umani.
However, single doses higher than 1000 mg have not been tested in controlled clinical trials.
Madankollu, dożi waħdiena ta ’ aktar minn 1000 mg ma ġewx ippruvati fi provi kliniċi kkontrollati.
Pharmacotherapeutic group: monoclonal antibodies, ATC code:
Kategorija farmakoterapewtika: antikorpi monoklonali, Kodiċi ATC:
Rituximab binds specifically to the transmembrane antigen, CD20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes.
Rituximab jintrabat speċifikament ma ’ l- antiġen trasmembran, CD20, fosfoprotein mhux glikosilat, li jkun jinsab f’ limfositi pre- B u B matura.
The antigen is expressed on > 95% of all B cell non-Hodgkin’ s lymphomas.
L- antiġen huwa espress fuq > 95% tal- limfomi mhux ta ’ Hodgkin taċ- ċellula B.
CD20 is found on both normal and malignant B cells, but not on haematopoietic stem cells, pro- B cells, normal plasma cells or other normal tissue.
CD20 jinsab kemm fuq ċelluli B normali kif ukoll fuq dawk kanċerużi, iżda mhux fuq ċelluli stemmi ematopojetiċi, ċelluli pro- B, ċelluli plażma normali jew saffi normali oħrajn.
This antigen does not internalise upon antibody binding and is not shed from the cell surface.
Dan l- antiġen ma jinternalizzax fuq l- irbit ta ’ l- antikorp u m’ huwhiex mgħotti mill- wiċċ taċ- ċellula.
CD20 does not circulate in the plasma as a free antigen and, thus, does not compete for antibody binding.
CD20 ma jiċċirkolax fil- plażma bħala antiġen liberu u, għaldaqstant, ma jikkompetix għall- irbit ta ’ l- antikorp.
16 The Fab domain of rituximab binds to the CD20 antigen on B lymphocytes and the Fc domain can recruit immune effector functions to mediate B cell lysis.
L- arja Fab tar- rituximab torbot ma ’ l- antiġen CD20 fuq limfositi B u l- arja Fc tkun tista ’ tqabbad funzjonijiet li jaffetwaw l- immunità sabiex iservu ta ’ medjaturi fil- lisi taċ- ċellula B.
Possible mechanisms of effector-mediated cell lysis include complement-dependent cytotoxicity (CDC) resulting from C1q binding, and antibody-dependent cellular cytotoxicity (ADCC) mediated by one or more of the Fcγ receptors on the surface of granulocytes, macrophages and NK cells.
Il- mekkaniżmi possibli ta ’ lisi taċ- ċellula effector- mediated jinkludu ċitotossiċità komplimentari- dipendenti (ĊKD) li tirriżulta minn irbit C1q, u ċitotossiċità ċellulari dipendenti fuq l- antikorp (ĊĊDA) medjata bir - reċetturi Fcγ, wieħed jew aktar, fuq il- wiċċ tal- granuloċiti, makrofaġi u ċelluli NK.
Rituximab binding to CD 20 antigen on B lymphocytes has also been demonstrated to induce cell death via apoptosis.
Ir- Rituximab li jorbot fuq l- antiġen CD 20 fuq il- limfoċiti B wera wkoll li jwassal għall- mewt taċ- ċelluli permezz ta ’ apoptosi.
Peripheral B cell counts declined below normal following completion of the first dose of MabThera.
17 L- għadd ta ’ ċelluli B periferali waqa ’ taħt in- normal wara t- teħid ta ’ l- ewwel doża ta ’ MabThera.
In patients treated for hematological malignancies, B cell repletion began within 6 months of treatment returning to normal levels between 9 and 12 months after completion of therapy.
Fil - pazjenti kkurati għal tumuri ematoloġiċi malinni, il- forniment ta ’ ċellula B beda fi żmien 6 xhur mill - kura biex reġa ’ lura għal- livelli normali bejn 9 u 12- il xahar wara li tlestiet it- terapija.
In rheumatoid arthritis patients, immediate depletion of B cells in the peripheral blood was observed following two infusions of 1000 mg MabThera separated by a 14 day interval.
F’ pazjenti morda bl- artrite rewmatika, tnaqqis immedjat taċ- ċelluli B fid- demm periferali ġie osservat wara żewġ infużjonijiet ta ’ 1000 mg MabThera separati b’ intervall ta ’ 14- il jum.
Peripheral blood B cell counts begin to increase from week 24 and evidence for repopulation is observed in the majority of patients by week 40, whether MabThera was administered as monotherapy or in combination with methotrexate.
L- għadd ta ’ ċelluli B fid- demm periferali jibda jiżdied minn ġimgħa 24 u evidenza għal popolazzjoni mill- ġdid hija osservata fil - maġġoranza tal- pazjenti sa ġimgħa 40, kemm jekk MabThera ngħata bħala monoterapija jew flimkien ma ’ methotrexate.
Clinical Experience in Non-Hodgkin’ s lymphoma and in chronic lymphocytic leukaemia
L- Esperjenza Klinika f’ limfoma Mhux ta ’ Hodgkin u f’ lewkimja limfoċitika kronika
Follicular non-Hodgkin's lymphoma
Limfoma follikulari mhux ta ’ Hodgkin
Monotherapy Initial treatment, weekly for 4 doses In the pivotal study, 166 patients with relapsed or chemoresistant low-grade or follicular B cell NHL received 375 mg/ m2 of MabThera as an intravenous infusion once weekly for four weeks.
Monoterapija Kura inizjali, darba fil- ġimgħa għal 4 dożi Fl- istudju ċentrali, 166 pazjent b’ NHL taċ- ċellula B follikulari jew ta ’ grad baxx kemoreżistenti jew li reġgħet tfaċċat ingħataw 375 mg/ m2 ta ’ MabThera bħala infużjoni fil- vini darba fil- ġimgħa għal erba ’ ġimgħat.
The overall response rate (ORR) in the intent-to-treat (ITT) population was 48% (CI95% 41% - 56%) with a 6% complete response (CR) and a 42% partial response (PR) rate.
Ir- rata ta ’ rispons ġenerali (RRĠ) fil- popolazzjoni bl- intenzjoni li tiġi trattata (ITT) kienet ta ’ 48% (CI95% 41% - 56%) b’ 6% rispons komplet (RK) u rata ta ’ 42% ta ’ rispons parzjali (RP).
The projected median time to progression (TTP) for responding patients was 13.0 months.
Il- medja taż- żmien previst għall- progresssjoni (ŻPP) għall- pazjenti li rrispondew kienet ta ’ 13. 0- il xahar.
38%), and higher in patients with chemosensitive relapse as compared to chemoresistant (defined as duration of response < 3 months) relapse (50% vs.
F’ analiżi tas- sottogruppi, ir- RRĠ kienet ogħla f’ pazjenti b’ sottotipi ħistoloġiċi IWF B, Ċ u D kif ikkomparati mas- sottotip IWF A (58% kontra 12%), ogħla f’ pazjenti li l- akbar leżjoni tagħhom kienet < 5 ċm kontra > 7 ċm fl- akbar dijametru (53% kontra 38%), u ogħla f’ pazjenti li reġgħu esperjenzaw il- kemosensittività meta kkumparata ma ’ dawk li reġgħu esperjenzaw il- kemoreżistenza (definita bħala tul ta ’ rispons ta ’ < 3 xhur) (50% kontra 22%).
ORR in patients previously treated with autologous bone marrow transplant (ABMT) was 78% versus 43% in patients with no ABMT.
Ir- RRĠ f’ pazjenti trattati preċedentement bi trapjant tal- mudullun awtologuż (TMA) kienet ta ’ 78% kontra 43% f’ pazjenti mingħajr TMA.
Neither age, sex, lymphoma grade, initial diagnosis, presence or absence of bulky disease, normal or high LDH nor presence of extranodal disease had a statistically significant effect (Fisher’ s exact test) on response to MabThera.
L- età, is- sess, il- grad tal- limfoma, id- dijanjosi inizjali, il- preżenza jew in- nuqqas ta ’ bulky disease, l- LDH normali jew għoli u lanqas il- preżenza ta ’ mard straordinarju ma kellhomx effett statistiku sinifikanti (it- test eżatt ta ’ Fisher) fuq ir- rispons għal MabThera.
A statistically significant correlation was noted between response rates and bone marrow involvement.
Ġiet innotata korrelazzjoni statistikament sinifikanti bejn ir- rati tar- rispons u l- involviment tal- mudullun.
40% of patients with bone marrow involvement responded compared to 59% of patients with no bone marrow involvement (p=0.0186).
40% tal- pazjenti b’ involviment tal - mudullun irrispondew, ikkumparati mad- 59% tal- pazjenti li ma ’ kellhomx involvement tal- mudullun (p=0. 0186).
This finding was not supported by a stepwise logistic regression analysis in which the following factors were identified as prognostic factors: histological type, bcl-2 positivity at baseline, resistance to last chemotherapy and bulky disease.
Din is- sejba ma kinitx appoġġjata minn analiżi tar- rigress loġistiku f’ termini ta ’ stadji li fiha ġew identifikati l- fatturi segwenti bħala fatturi pronjostiċi: it- tip ħistoloġiku, il- pożittività bcl- 2 fil- linja bażi, ir- reżistenza għall- aħħar kimoterapija u l- bulky disease.
Initial treatment, weekly for 8 doses In a multi-centre, single-arm study, 37 patients with relapsed or chemoresistant, low grade or follicular B cell NHL received 375 mg/ m2 of MabThera as intravenous infusion weekly for eight doses.
Kura inizjali, darba fil- ġimgħa għal 8 dożi Fi studju speċifiku b’ aktar minn ċentru wieħed, 37 pazjent b’ NHL taċ- ċellula B follikulari jew ta ’ grad baxx kemoreżistenti jew li reġgħet tfaċċat ingħataw 375 mg/ m2 ta ’ MabThera bħala infużjoni fil- vini kull ġimgħa għal tmien dożi.
The ORR was 57% (95% Confidence interval (CI); 41% – 73%; CR 14%, PR 43%) with a projected median TTP for responding patients of 19.4 months (range 5.3 to 38.9 months).
Ir- RRĠ kienet ta ’ 57% (Intervall ta ’ kunfidenza (CI) ta ’ 95%; 41% – 73%; RK 14%, RP 43%) b’ medja ta ’ ŻPP għal pazjenti li rrispondew ta ’ 19. 4 xhur (firxa minn 5. 3 sa 38. 9 xhur).
Initial treatment, bulky disease, weekly for 4 doses In pooled data from three studies, 39 patients with relapsed or chemoresistant, bulky disease (single lesion ≥ 10 cm in diameter), low grade or follicular B cell NHL received 375 mg/ m2 of MabThera as intravenous infusion weekly for four doses.
Kura inizjali, bulky disease, darba fil- ġimgħa għal 4 dożi F’ ġabra ta ’ informazjoni komuni minn tliet studji, 39 pazjent b’ NHL taċ- ċellula B follikulari jew ta ’ grad baxx kemoreżistenti jew li reġgħet tfaċċat, b’ bulky disease (leżjoni waħda ≥ 10 ċm fid- dijametru) ingħataw 375 mg/ m2 ta ’ MabThera bħala infużjoni fil- vini kull ġimgħa għal erba ’ dożi.
The ORR was 36% (CI95% 21% – 51%; CR 3%, PR 33%) with a median TTP for responding patients of 9.6 months (range 4.5 to 26.8 months).
Ir- RRĠ kienet ta ’ 36% (CI95% 21% – 51%; RK 3%, RP 33%) b’ medja ta ’ ŻPP għal pazjenti li rrispondew ta ’ 9. 6 xhur (firxa minn 4. 5 sa 26. 8 xhur).
Re-treatment, weekly for 4 doses In a multi-centre, single-arm study, 58 patients with relapsed or chemoresistant low grade or follicular B cell NHL, who had achieved an objective clinical response to a prior course of MabThera, were re- treated with 375 mg/ m2 of MabThera as intravenous infusion weekly for four doses.
Kura mill- ġdid, darba fil- ġimgħa għal 4 dożi Fi studju b’ aktar minn ċentru wieħed, 58 pazjent b’ NHL taċ- ċellula B follikulari jew ta ’ grad baxx kemoreżistenti jew li reġgħet tfaċċat, li jkunu waslu għal rispons kliniku oġġettiv għal kors preċedenti ta ’ MabThera, ġew trattati mill- ġdid bi 375 mg/ m2 ta ’ MabThera bħala infużjoni fil- vini kull ġimgħa għal erba ’ dożi.
Three of the patients had received two courses of MabThera before enrollment and thus were given a third course
Tlieta mill- pazjenti kienu ngħataw żewġ korsijiet ta ’ MabThera qabel ma daħlu u għalhekk waqt l- istudju ingħataw it- tielet kors.
Two patients were re-treated twice in the study.
Żewġ pazjenti ġew trattati mill- ġdid darbtejn fl- istudju.
For the 60 re-treatments on study, the ORR was 38% (CI95% 26% – 51%; 10% CR, 28% PR) with a projected median TTP for responding patients of 17.8 months (range 5.4 – 26.6).
Għas- 60 kura mill- ġdid fl- istudju, ir- RRĠ kienet ta ’ 38% (CI95% 26% – 51%; 10% RK, 28% RP)
This compares favourably with the TTP achieved after the prior course of MabThera (12.4 months).
Dan jikkompara b’ mod favorevoli maż- ŻPP milħuq wara l- kors preċedenti ta ’ MabThera (12. 4 xhur).