qanastek/EMEA-V3 huggingface dataset:
Initial treatment, in combination with chemotherapy In an open-label randomised trial, a total of 322 previously untreated patients with follicular lymphoma were randomised to receive either CVP chemotherapy (cyclophosphamide 750 mg/ m2, vincristine 1.4 mg/ m2 up to a maximum of 2 mg on day 1, and prednisolone 40 mg/ m2/ day on days 1 -5) every 3 weeks for 8 cycles or MabThera 375 mg/ m2 in combination with CVP (R-CVP).
Kura inizjali, flimkien ma ’ kimoterapija Fi prova klinika tat- tip open- label u randomised, total ta ’ 322 pazjent b’ limfoma follikulari li ma kinux irċevew kura qabel ġew randomised biex jirċievu kimoterapija (cyclophosphamide 750 mg/ m2, vincristine 1. 4 mg/ m2 sa massimu ta ’ 2 mg fl- ewwel jum, u prednisolone 40 mg/ m2/ kuljum mill- ewwel sal- ħames jum) kull 3 ġimgħat għal 8 ċikli jew MabThera 375 mg/ m2 flimkien ma ’ CVP (R- CVP).
MabThera was administered on the first day of each treatment cycle.
MabThera ngħata fl- ewwel jum ta ’ kull ċiklu ta ’ kura.
A total of 321 patients (162 R-CVP, 159 CVP) received therapy and were analysed for efficacy.
Total ta ’ 321 pazjent (162 R- CVP, 159 CVP) irċevew it- terapija u ġew analizzati għall- effikaċja.
The median follow up of patients was 53 months.
Iż- żmien medju sal- vista ta ’ wara għall- pazjenti kien ta ’ 53 xahar.
R-CVP led to a significant benefit over CVP for the primary endpoint, time to treatment failure (27 months vs.
R- CVP wassal għal vantaġġ sinifikanti fuq CVP għall- mira primarja, iż- żmien sal - falliment tal- kura (27 xahar vs.
6.6 months, p < 0.0001, log-rank test).
6. 6 xhur, p < 0. 0001, test log- rank).
The proportion of patients with a tumour response (CR, CRu, PR) was significantly higher (p < 0.0001 Chi-Square test) in the R-CVP group (80.9%) than the CVP group (57.2%).
Il- proporzjon ta ’ pazjenti b’ rispons tat- tumur (CR, CRu, PR) kien sinifikattivament ogħla (p < 0. 0001 test Chi- Square) fil- grupp ta ’ R- CVP (80. 9%) milli fil- grupp ta ’ CVP (57. 2%).
Treatment with R-CVP significantly prolonged the time to disease progression or death compared to CVP, 33.6 months and 14.7 months, respectively (p < 0.0001, log-rank test).
Kura b’ R- CVP tawwlet b’ mod sinifikanti iż- żmien sal - progressjoni tal- marda jew sal- mewt meta mqabbel ma ’ CVP, b’ 33. 6 xhur u 14. 7 xhur, rispettivament (p < 0. 0001, test log- rank).
The median duration of response was 37.7 months in the R-CVP group and was 13.5 months in the CVP group (p < 0.0001, log-rank test).
Il- perijodu medju ta ’ rispons kien 37. 7 xhur fil- grupp ta ’ R- CVP u kien ta ’ 9. 8 xhur fil- grupp ta ’ CVP (p < 0. 0001, test log- rank).
The difference between the treatment groups with respect to overall survival showed a significant clinical difference (p=0.029, log-rank test stratified by center): survival rates at 53 months were 80.9% for patients in the R-CVP group compared to 71.1% for patients in the CVP group
Id- differenza bejn il- gruppi ta ’ kura f’ dak li jikkonċerna is- sopravivenza globali wriet differenza klinika sinifikanti (p=0. 029, test log- rank stratifikat biċ- ċentru): rati ta ’ sopravivenza wara 53 xahar kienu 80. 9% għall- pazjenti fil- grupp ta ’ R- CVP meta mqabbel ma ’ 71. 1% għall- pazjenti fil- grupp ta ’ CVP.
Results from three other randomized trials using MabThera in combination with chemotherapy regimen other than CVP (CHOP, MCP, CHVP/ Interferon-α) have also demonstrated significant improvements in response rates, time-dependent parameters as well as in overall survival.
Riżultati minn tliet provi randomised oħra bl- użu ta ’ MabThera flimkien ma ’ kors ta ’ kimoterapija barra minn CVP (CHOP, MCP, CHVP/ Interferon- α) ukoll urew titjib sinifikanti fir- rati ta ’ rispons, fil - parametri li huma dipendenti mill- ħin kif ukoll fis- sopravivenza globali.
Key results from all four studies are summarized in table 3.
Tabella 3
Summary of key results from four phase III randomized studies evaluating the benefit of MabThera with different chemotherapy regimens in follicular lymphoma
Sommarju ta ’ riżultati kruċjali minn erba ’ studji randomised ta ’ fażi III li vvalutaw il- benefiċċju ta ’ MabThera ma ’ korsijiet differenti ta ’ kimoterapija f’ limfoma follikulari
Median Median Treatment, CR,
TTF/ PFS/ EFS FU Rati ta ’ Kura, CR, Medju Medju, ORR,%
Study
Studju
months mo Median TTP:
OS, n% Xhur% mo TTP Medju:
CVP, 159 57 10 14.7
53- xahar CVP, 159 57 10 14. 7 71. 1 53
53 33.6 R-CVP, 162 81 41
33. 6 80. 9 R- CVP, 162 81 41 P < 0. 0001 p=0. 029
P < 0.0001
18- xahar TTF Medju:
CHOP, 205
2. 6 snin CHOP, 205 90 GLSG’ 00
2.6 years
R- CHOP,
90
Ma ntlaħaqx
Not reached p < 0.001
p < 0. 001
Median PFS:
48- xahar PFS Medju:
Not reached
Ma ntlaħaqx
p < 0.0001
p < 0. 0001
0.0096
0. 0096
Median EFS:
42- xahar CHVP- IFN, EFS Medju:
IFN, 175
p = 0. 029 IFN, 175
p = 0.029
EFS – Sopravivenza Mingħajr Avveniment
EFS – Event Free Survival TTP – Time to progression or death PFS – Progression-Free Survival TTF – Time to Treatment Failure OS rates – survival rates at the time of the analyses
19 TTP – Żmien sal- progressjoni jew sal- mewt PFS – Sopravivenza Mingħajr Progressjoni TTF – Żmien sal- Falliment tal- Kura Rati ta ’ OS – rati ta ’ sopravivenza fi żmien l- analiżi
Maintenance therapy In a prospective, open label, international, multi-centre, phase III trial, 465 patients with relapsed/ refractory follicular NHL were randomised in a first step to induction therapy with either CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone; n=231) or MabThera plus CHOP (R-CHOP, n=234).
Fi prova prospettiva, internazzjonali, tat- tip open label, multi- ċentri, ta ’ fażi III, 465 pazjent b’ NHL follikulari li reġgħet tfaċċat/ refrattarja ntgħażlu b’ mod każwali fl- ewwel pass għal terapija ta ’ induzzjoni b’ CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone; n=231) jew MabThera flimkien ma ’ CHOP (R- CHOP, n=234).
The two treatment groups were well balanced with regard to baseline characteristics and disease status.
Iż- żewġ gruppi ta ’ kura kienu bilanċjati tajjeb fir - rigward tal- karatteristiċi bażiċi u l- istat tal- marda.
A total of 334 patients achieving a complete or partial remission following induction therapy were randomised in a second step to MabThera maintenance therapy (n=167) or observation (n=167).
Total ta ’ 334 pazjent li kisbu remissjoni kompleta jew parzjali wara terapija ta ’ induzzjoni ġew randomised fi stadju ieħor għal terapija ta ’ manteniment b’ MabThera (n+167) jew osservazzjoni (n+167).
MabThera maintenance treatment consisted of a single infusion of MabThera at 375 mg/ m2 body surface area given every 3 months until disease progression or for a maximum period of two years.
Il- kura ta ’ manteniment b’ MabThera kienet tikkonsisti minn infużjoni waħda ta ’ MabThera f’ doża ta ’ 375 mg/ m2 ta ’ arja tas- superfiċje tal- ġisem sakemm damet tavanza l- marda jew għal perijodu massimu ta ’ sentejn.
The final efficacy analysis included all patients randomized to both parts of the study.
L- analiżi finali ta ’ l- effikaċja kienet tinkludi l- pazjenti kollha randomised għaż- żewġ partijiet ta ’ l - istudju.
After a median observation time of 31 months for patients randomised to the induction phase, R-CHOP significantly improved the outcome of patients with relapsed/ refractory follicular NHL when compared to CHOP (see Table 4).
Wara perijodu medju ta ’ osservazzjoni ta ’ 31 xahar għall- pazjenti randomised għall- fażi ta ’ induzzjoni, R- CHOP tejbet b’ mod sinifikanti r- riżultat tal- pazjenti b’ NHL li reġgħet tfaċċat/ refrattarja meta mqabbel ma ’ CHOP (ara Tabella 4).
19 Table 4
Tabella 4 Effikaċja Primarja 1)
R-CHOP (31 months median observation time)
Fażi ta ’ induzzjoni: ħarsa ġenerali tar- riżultati ta ’ l- effikaċja għal CHOP vs R - CHOP (perijodu medjan ta ’ osservazzjoni ta ’ 31 xahar) CHOP R- CHOP Valur p Tnaqqis tar - riskju1) ORR2) 74% 87% 0. 0003 na CR2) 16% 29% 0. 0005 na PR2) 58% 58% 0. 9449 na
Estimates were calculated by hazard ratios 2) Last tumour response as assessed by the investigator.
L- istimi ġew ikkalkulati bil- proporzjonijiet ta ’ periklu 2) L- aħħar rispons tat- tumur kif evalwat mill- investigatur.
The “ primary” statistical test for “ response” was the trend test of CR versus PR versus non-response (p < 0.0001) Abbreviations:
It- test statistiku “ primarju ” għar - “ rispons ” kien it- test tat- tendenza ta ’ CR kontra PR kontra l- ebda rispons (p < 0. 0001) Abbrevjazzjonijiet:
NA, not available; ORR: overall response rate; CR: complete response; PR: partial response
NA, mhux disponibbli; ORR: rata ta ’ rispons globali; CR: rispons totali; PR: rispons parzjali
For patients randomized to the maintenance phase of the trial, the median observation time was 28 months from maintenance randomisation.
Fil- każ tal- pazjenti magħżula b’ mod każwali għall- fażi ta ’ manteniment tal- prova, il- perijodu medju ta ’ osservazzjoni kien ta ’ 28 xahar mill- għażla każwali tal- manteniment.
Maintenance treatment with MabThera led to a clinically relevant and statistically significant improvement in the primary endpoint, PFS, (time from maintenance randomisation to relapse, disease progression or death) when compared to observation alone (p < 0.0001 log-rank test). The median PFS was 42.2 months in the MabThera maintenance arm compared to 14.3 months in the observation arm.
Il- kura ta ’ manteniment b’ MabThera wasslet għal titjib klinikament rilevanti u statistikament sinifikanti fil- punt finali primarju, PFS, (żmien mill- għażla każwali tal- manteniment sar- rikaduta, progressjoni tal- marda jew mewt) meta pparagunata ma ’ osservazzjoni waħedha (p < 0. 0001 log- rank test).
Using a cox regression analysis, the risk of experiencing progressive disease or death was reduced by 61% with MabThera maintenance treatment when compared to observation (95% CI; 45 %-72%).
Il- PFS medju kien ta ’ 42. 2 xahar fil- grupp ta ’ manteniment b’ MabThera, ipparagunat ma ’ 14. 3- il xahar fil- grupp ta ’ osservazzjoni.
Kaplan-Meier estimated progression- free rates at 12 months were 78% in the MabThera maintenance group vs.
Bl - użu ta ’ analiżi tar- rigressjoni cox, ir- riskju li jkunu esperjenzati mard progressiv jew mewt tnaqqas b’ 61% bil- kura ta ’ manteniment MabThera meta mqabbel ma ’ l- osservazzjoni (95% CI; 45% - 72%).
57% in the observation group.
Ir- rati ta ’ nuqqas ta ’ progressjoni stmati bil- Kaplan- Meier wara 12- il xahar kienu 78% fil- grupp ta ’ manteniment b’ MabThera vs 57% fil- grupp ta ’ osservazzjoni.
An analysis of overall survival confirmed the significant benefit of MabThera maintenance over observation (p=0.0039 log-rank test).
Analiżi tas- sopravivenza globali kkonfermat il- vantaġġ sinifikanti ta ’ manteniment b’ MabThera fuq l- osservazzjoni (p=0. 0039 log- rank test).
MabThera maintenance treatment reduced the risk of death by 56% (95% CI; 22 %-75%).
Il- kura ta ’ manteniment b’ MabThera naqqset ir- riskju ta ’ mewt b’ 56% (95% CI; 22% - 75%).
Table 5
20 Tabella 5
Maintenance phase: overview of efficacy results MabThera vs. observation (28 months median observation time)
Fażi ta ’ manteniment: ħarsa ġenerali tar- riżultati ta ’ l- effikaċja MabThera vs. osservazzjoni (perijodu medjan ta ’ osservazzjoni ta ’ 28 xahar)
Kaplan-Meier Estimate of
Parametru ta ’ l- Effikaċja
Median Time to Event (Months)
Stima Kaplan- Meier tal- Perijodu Medjan sa Avveniment (xhur)
Reduction
Tnaqqis tar - Riskju
Observation MabThera (N = 167) (N=167)
Osservazzjo ni (N = 167)
Log-Rank p value
Log- Rank valur p
Progression-free survival (PFS)
Sopravivenza mingħajr progressjoni (PFS)
14.3 42.2
42. 2
Overall Survival
Sopravivenza globali
Time to new lymphoma treatment
Żmien sa kura ġdida kontra l - limfoma
38.8
38. 8
Disease-free survivala
Sopravivenza ħielsa mill- mardaa
53.7
53. 7
Subgroup Analysis PFS
Analiżi tas- sottogruppi PFS 71% < 0. 0001
11.6
11. 6
37.5
37. 5
< 0.0001
0. 0071
14.3
14. 3
37.8
52. 8
CHOP
14. 3
NR NR
37. 8
0.0348
OS 55% 0. 0348 NR
55%
CHOP
R-CHOP
NR
20 NR: not reached; a: only applicable to patients achieving a CR
NR: mhux milħuq; a: tapplika biss għall- pazjenti li kisbu CR
The benefit of MabThera maintenance treatment was confirmed in all subgroups analysed, regardless of induction regimen (CHOP or R-CHOP) or quality of response to induction treatment (CR or PR) (table 5).
Il- vantaġġ tal- kura ta ’ manteniment b’ MabThera ġie kkonfermat fis- sottogruppi kollha kkonfermati, irrispettivament mir- reġim ta ’ induzzjoni (CHOP jew R- CHOP) jew il- kwalità tar- rispons għall- kura ta ’ induzzjoni (CR jew PR) (tabella 5).
22.1 months, p=0.0071).
Il- kura ta ’ manteniment b’ MabThera tawlet b’ mod sinifikanti l- PFS medja fil- pazjenti li rrispondew għat- terapija ta ’ induzzjoni CHOP (PFS medja 37. 5 xahar vs 11. 6- il xahar, p < 0. 0001) kif ukoll f’ dawk li rrispondew għall- induzzjoni b’ R- CHOP (PFS medja 51. 9 xahar vs 22. 1 xahar, p=0. 0071).
Although subgroups were small, MabThera maintenance treatment provided a significant benefit in terms of overall survival for both patients responding to CHOP and patients responding to R-CHOP, although longer follow-up is required to confirm this observation.
Għalkemm is- sottogruppi kienu żgħar, il- kura ta ’ manteniment b’ MabThera pprovdiet vantaġġ sinifikanti f’ termini ta ’ sopravivenza globali kemm għall- pazjenti li rrispondew għal CHOP kif ukoll għall- pazjenti li rrispondew għal R- CHOP, għalkemm huwa meħtieġ perijodu itwal ta ’ wara l- kura biex tiġi kkonfermata din l- osservazzjoni.
Diffuse large B cell non-Hodgkin’ s lymphoma
Limfoma mhux ta ’ Hodgkin taċ- ċellula B kbira mxerrda
In a randomised, open-label trial, a total of 399 previously untreated elderly patients (age 60 to 80 years) with diffuse large B cell lymphoma received standard CHOP chemotherapy (cyclophosphamide 750 mg/ m2, doxorubicin 50 mg/ m2, vincristine 1.4 mg/ m2 up to a maximum of 2 mg on day 1, and prednisolone 40 mg/ m2/ day on days 1-5) every 3 weeks for eight cycles, or MabThera 375 mg/ m2 plus CHOP (R-CHOP).
Fi prova tat- tip open label magħmula b’ għażla każwali, total ta ’ 399 pazjent anzjani mhux trattati preċedentement (età bejn is- 60 u t- 80 sena) b’ limfoma taċ- ċellula B kbira mxerrda ngħataw kimoterapija CHOP standard (cyclophosphamide 750 mg/ m2, doxorubicin 50 mg/ m2, vincristine 1. 4 mg/ m2 sa massimu ta ’ 2 mg fl- ewwel ġurnata, u prednisolone 40 mg/ m2/ ġurnata fil- ġranet 1- 5) kull 3 ġimgħat għal tmien ċikli, jew MabThera 375 mg/ m2 kif ukoll CHOP (R- CHOP).
MabThera was administered on the first day of the treatment cycle.
MabThera kien amministrat fl- ewwel ġurnata taċ- ċiklu ta ’ kura.
The final efficacy analysis included all randomised patients (197 CHOP, 202 R-CHOP), and had a median follow-up duration of approximately 31 months.
L- analiżi ta ’ l- effikaċja finali kienet tinkludi l- pazjenti meħudin b’ mod każwali kollha (197 CHOP, 202 R- CHOP), u kellha medja ta ’ tul ta ’ żmien ta ’ osservanza wara l- kura ta ’ madwar 31 xahar.
The two treatment groups were well balanced in baseline disease characteristics and disease status.
Iż - żewġ gruppi ta ’ kura kienu bbilanċjati tajjeb fil- karatteristiċi bażiċi tal- mard u fl- istat tal- mard.
The final analysis confirmed that R-CHOP treatment was associated with a clinically relevant and statistically significant improvement in the duration of event-free survival (the primary efficacy parameter; where events were death, relapse or progression of lymphoma, or institution of a new anti-lymphoma treatment) (p = 0.0001).
L - analiżi finali kkonfermat li l- kura R- CHOP kienet assoċjata ma ’ titjib kliniku rilevanti u statistikament sinifikanti fit- tul ta ’ żmien ta ’ sopravivenza mingħajr episodji (il- parametru ta ’ effikaċja primarju; fejn
Kaplan Meier estimates of the median duration of event-free survival were 35 months in the R-CHOP arm compared to 13 months in the CHOP arm, representing a risk reduction of 41%.
L- estimi ta ’ Kaplan Meier tat- tul ta ’ żmien medju ta ’ sopravivenza mingħajr episodji kienu 35 xahar fl- R- CHOP ikkumparat mat- 13- il xahar fis- CHOP, li jirrappreżentaw tnaqqis tar- riskju ta ’ 41%.
At 24 months, estimates for overall survival were 68.2% in the R-CHOP arm compared to 57.4% in the CHOP arm.
F’ 24 xahar, l- estimi ta ’ sopravivenza ġenerali kienu ta ’ 68. 2% fl- R- CHOP ikkumparati ma ’ 57. 4% fis- CHOP.
A subsequent analysis of the duration of overall survival, carried out with a median follow-up duration of 60 months, confirmed the benefit of R-CHOP over CHOP treatment (p=0.0071), representing a risk reduction of 32%.
Analiżi sussegwenti tat- tul tas- sopravivenza globali, imwettqa b’ tul ta ’ żmien medju ta ’ wara l- kura ta ’ 60 xahar, ikkonfermat il- benefiċċju tal- kura R- CHOP fuq dik CHOP (p=0. 0071), li tirrappreżenta tnaqqis ta ’ 32%.
The analysis of all secondary parameters (response rates, progression-free survival, disease-free survival, duration of response) verified the treatment effect of R-CHOP compared to CHOP.
L- analiżi tal- parametri sekondarji kollha (rati tar- rispons, sopravivenza mingħajr progressjoni, sopravivenza mingħajr mard, tul taż- żmien tar- rispons) ivverifikat l- effett tal- kura ta ’ R- CHOP meta kkumparat ma ’ CHOP.
The complete response rate after cycle 8 was 76.2% in the R-CHOP group and 62.4% in the CHOP group (p=0.0028).
Ir- rata ta ’ rispons komplet wara t- 8 ċiklu kienet ta ’ 76. 2% fil- grupp ta ’ l- R - CHOP u ta ’ 62. 4% fil- grupp tas- CHOP (p=0. 0028).
The risk of disease progression was reduced by 46% and the risk of relapse by 51%.
Ir- riskju ta ’ progressjoni fil- mard kien imnaqqas b’ 46% u r- riskju li terġa ’ titfaċċa b’ 51%.
In all patients subgroups (gender, age, age adjusted IPI, Ann Arbor stage, ECOG, β 2 microglobulin, LDH, albumin, B symptoms, bulky disease, extranodal sites, bone marrow involvement), the risk ratios for event-free survival and overall survival (R-CHOP compared with CHOP) were less than 0.83 and 0.95 respectively.
Fis- sottogruppi ta ’ pazjenti kollha (sess, età, IPI aġġustat, stadju ta ’ Ann Arbor, ECOG, β2 mikroglobulina, LDH, albumin, sintomi- B, bulky disease, siti estranodali, involvement tal- mudullun), il- proporzjon tar- riskju għal sopravivenza mingħajr episodji u ta ’ sopravivenza ġenerali (R- CHOP ikkumparat ma ’ CHOP) kienu inqas minn 0. 83 u 0. 95 rispettivament.
R-CHOP was associated with improvements in outcome for both high- and low-risk patients according to age adjusted IPI.
R- CHOP ġie assoċjat ma ’ titjib fir- riżultat kemm f’ pazjenti b’ riskju baxx kif ukoll f’ dawk b’ riskju għoli skond l- IPI aġġustat skond l- età.
Clinical laboratory findings Of 67 patients evaluated for human anti-mouse antibody (HAMA), no responses were noted.
Sejbiet kliniċi tal- laboratorju Mis- 67 pazjent evalwat għall- antikorp kontra l- ġrieden uman (HAMA), ma kien innutat l- ebda rispons.
Of 356 patients evaluated for HACA, 1.1% (4 patients) were positive.
Mit- 356 pazjent evalwat għall- HACA, 1. 1% (4 pazjenti) kienu pożittivi.
In an open-label randomized trial, a total of 817 previously untreated patients with CLL were randomized to receive either FC chemotherapy (fludarabine 25 mg/ m2, cyclophosphamide 250 mg/ m2, days 1-3) every 4 weeks for 6 cycles or MabThera in combination with FC (R-FC).
Fi prova open- label u randomised, total ta ’ 817 pazjent b’ CLL li ma kienux ikkurati minn qabel kienu randomised biex jirċievu kimoterapija ta ’ FC (fludarabine 25mg/ m2, cyclophosphamide 250 mg/ m2, ġranet 1- 3) kull 4 ġimgħat għal 6 ċikli jew MabThera flimkien ma ’ FC (R- FC).
MabThera was administered at a dosage of 375 mg/ m2 during the first cycle one day prior to chemotherapy and at a dosage of 500 mg/ m2 on day 1 of each subsequent treatment cycle.
MabThera kien mogħti f’ dożaġġ ta ’ 375 mg/ m2 waqt l- ewwel ċiklu ġurnata qabel il- kimoterapija u f’ dożaġġ ta ’ 500 mg/ m2 fl - ewwel ġurnata ta ’ kull ċiklu ta ’ kura sussegwenti.
A total of 810 patients (403 R-FC, 407 FC) were analyzed for efficacy (Table 6).
Total ta ’ 810 pazjent (403 R- FC, 407 FC) kienu analizzati għall- effikaċja (Tabella 6).
The primary endpoint of progression-free survival was 40 months median in the R-FC group and 32 months in the FC group (p < 0.0001, log-rank test).
Il- mira primarja ta ’ sopravivenza mingħajr progressjoni kienet ta ’ medjan ta ’ 40 xahar fil- grupp ta ’ R - FC u 32 xahar fil- grupp ta ’ FC (p < 0. 0001, test log- rank).
The analysis of overall survival showed an improved survival in favour of the R-FC arm (p=0.0427, log-rank test), however longer follow-up is
L- analiżi tas- sopravivenza globali wriet sopravivenza mtejba favur il- grupp ta ’ R- FC (p=0. 0427, test log- rank), iżda huma meħtieġa visti ta ’ wara aktar fit- tul biex din l- osservazzjoni tkun ikkonfermata.
The benefit in terms of PFS was consistently observed in most patient subgroups analyzed according to disease risk at baseline.
Il- benefiċċju f’ termini ta ’ PFS kien osservat b’ mod konsistenti fil- biċċa l- kbira tas- sottogruppi ta ’ pazjenti analizzati skond ir- riskju tal - marda fil- linja bażi.
Table 6
22 Tabella 6
First-line treatment of chronic lymphocytic leukaemia
Kura preferita ta ’ lewkimja limfoċitika kronika
Overview of efficacy results for MabThera plus FC vs.
ta ’ l- effikaċja għal MabThera flimkien ma ’ FC vs.
FC alone (20.7 months median observation time)
medjan ta ’ osservazzjoni ta ’ 20. 7 xahar)
Efficacy Parameter
Stima Kaplan- Meier tal- Perijodu
Event Free Survival
Sopravivenza Mingħajr Avveniment
31.1
31. 1
Response rate (CR, nPR, or PR)
Rata ta ’ Rispons (CR, nPR, jew PR)
72.7%
72. 7%
86.1%
86. 1%
CR rates
Rati ta ’ CR
17.2%
17. 2%
36.0%
36. 0%
Duration of response* Disease free survival (DFS)** Time to new treatment
Tul tar- rispons * Sopravivenza ħielsa mill- marda (DFS) **
34.7 NR.
34. 7 NR.
Response rate and CR rates analysed using Chi-squared Test. *: only applicable to patients achieving a CR, nPR, PR; applicable **: only applicable to patients achieving a CR;
Rata ta ’ rispons u rati ta ’ CR analizzati bl- użu tat- Test Chi- squared. *: jgħodd biss għall- pazjenti li laħqu CR, nPR, PR; **: jgħodd biss għall- pazjenti li laħqu CR;
NR: not reached
NR: ma ntlaħaqx
n. a. not
n. a. ma jgħoddx
Progression-Free Survival according to Binet stage (ITT)
Sopravivenza Mingħajr Progressjoni skond l- istadju Binet (ITT)
Progression-free survival (PFS)
Sopravivenza Mingħajr Progressjoni (PFS)
Number of patients
Numru ta ’ pazjenti
Hazard Ratio (95% CI)
Proporzjon ta ’ Periklu (95% CI)
p-value (Wald test, not
valur p (test ta ’ Wald, mhux
adjusted)
aġġustat)
Binet C
Binet Ċ
Confidence Interval
Intervall ta ’ Kunfidenza
Results from other supportive studies using MabThera in combination with other chemotherapy regimens (including CHOP, FCM, PC, PCM) for the treatment of CLL patients have also demonstrated high overall response rates with promising PFS rates without adding relevant toxicity to the treatment.
Riżultati minn studji oħra ta ’ sapport bl- użu ta ’ MabThera flimkien ma ’ korsijiet oħra ta ’ kimoterapija (inkluż CHOP, FCM, PC, PCM) għall- kura ta ’ pazjenti b’ CLL ukoll urew rati ta ’ rispons globali għolja b’ rati ta ’ PFS b’ derha tajba mingħajr żjieda fit- tossiċità rilevanti tal- kura.
Clinical Experience in Rheumatoid Arthritis
Esperjenza Klinika fl- Artrite Rewmatika
The efficacy and safety of MabThera in alleviating the symptoms and signs of rheumatoid arthritis was demonstrated in three randomized, controlled, double-blind, multicenter studies.
L- effikaċja u s- sigurtà ta ’ MabThera fis- solliev tas- sintomi u s- sinjali ta ’ l- artrite rewmatika ġew murija fi tliet studji kkontrollati, tat- tip double- blind, multi- ċentri, magħmula b’ għażla każwali.
22 Study 1 was a double blind comparative study which included 517 patients that had experienced an inadequate response or intolerance to one or more TNF inhibitor therapies.
Studju 1 kien studju komparattiv tat- tip double- blind li kien jinkludi 517- il pazjent li kienu esperjenzaw rispons inadegwat jew intolleranza għal terapija waħda jew aktar ta ’ inibizzjoni tat- TNF.
Eligible patients had active rheumatoid arthritis for at least 6 months, diagnosed according to the criteria of the American College of Rheumatology (ACR), with swollen joint count (SJC) (8 (66 joint count), and tender joint count (TJC) (8 (68 joint count) and elevated CRP or ESR.
23 kriterji tal- Kulleġġ Amerikan tar- Rewmatoloġija (ACR), bl- għadd ta ’ ġogi minfuħa (SJC – swollen joint count) (8 (għadd tal- ġogi 66) u l- għadd ta ’ ġogi sensittivi (TJC – tender joint count) (8 (għadd tal- ġogi 68) u CRP jew ESR għoli.
The primary endpoint was the percent of patients who achieved an ACR20 response at week 24.
Il- punt finali primarju kien il- perċentwali ta ’ pazjenti li kisbu rispons ACR20 f’ ġimgħa 24.
Patients received two 1000 mg intravenous infusions of MabThera, each following an intravenous infusion of 100 mg methylprednisone and separated by an interval of 15 days.
Il- pazjenti rċevew żewġ infużjonijiet fil- vini ta ’ 1000 mg ta ’ MabThera, kull waħda segwita minn infużjoni fil- vini ta ’ 100 mg methylprednisone u separati b’ intervall ta ’ 15- il ġurnata.
All patients received concomitant oral methotrexate (10-25 mg/ week) and 60 mg oral prednisone on days 2-7 and 30 mg on days 8-14 following the first infusion.
Il- pazjenti kollha rċevew methotrexate orali konkomitanti (10- 25 mg/ ġimgħa) u 60 mg prednisone orali fil- jiem 2- 7 u 30 mg fil- jiem 8- 14 wara l- ewwel infużjoni.
Patients were followed beyond week 24 for long term endpoints, including radiographic assessment at 56 weeks.
Il- pazjenti ġew segwiti lilhinn minn ġimgħa 24 għal punti finali fuq perijodu fit- tul, fosthom evalwazzjoni radjografika wara 56 ġimgħa.
During this time 81% of patients, from the original placebo group received rituximab between weeks 24 an 56, under an open label extension study protocol.
F’ dan iż- żmien 81% tal- pazjenti mill- grupp oriġinali fuq il- plaċebo rċevew rituximab bejn ġimgħa 24 u ġimgħa 56, taħt protokoll ta ’ studju ta ’ estensjoni tat- tip open label.
Study 2 was a randomized, double-blind, double-dummy, controlled, 3 x 3 multifactorial study which compared two different dose levels of rituximab given with or without one of two peri infusional corticosteroid regimens in combination with weekly methotrexate in patients with active rheumatoid arthritis which had not responded to treatment with 1 to 5 other DMARDs.
Studju 2 kien studju double- blind, double- dummy, ikkontrollat, 3 x 3 multifattorjali, magħmul b’ għażla każwali, li qabbel żewġ livelli ta ’ dożi differenti mogħtija bi jew mingħajr wieħed minn żewġ reġimi ta ’ kortikosterojdi peri- infużjonali flimkien ma ’ methotrexate darba fil- ġimgħa f’ pazjenti b’ artrite rewmatika attiva li ma kinux irrispondew għall- kura b’ 1 sa 5 DMARDs oħra.
Study 3 was a double-blind, double-dummy, controlled study evaluating rituximab monotherapy, and rituximab in combination with either cyclophosphamide or methotrexate in patients with active rheumatoid arthritis which had not responded to one or more prior DMARDs
Studju 3 kien studju double- blind, double- dummy, ikkontrollat li evalwa l- monoterapija rituximab, u rituximab flimkien ma ’ cyclophosphamide jew methotrexate f’ pazjenti b’ artrite rewmatika attiva li ma kinux irrispondew għal DMARD waħda jew aktar preċedenti.
The comparator group in all three studies was weekly methotrexate (10-25 mg weekly).
Il- grupp komparatur f’ dawn it- tliet studji kien methotrexate darba fil- ġimgħa (10- 25 mg darba fil - ġimgħa).
Disease activity outcomes In all three studies, rituximab 2 x 1000 mg significantly increased the proportion of patients achieving at least a 20% improvement in ACR score compared with patients treated with methotrexate alone (Table 7).
Riżultati ta ’ l- attività tal- marda Fit- tliet studji kollha, rituximab 2 x 1000 mg żied b’ mod sinifikanti l- proporzjon ta ’ pazjenti li kisbu mill- anqas 20% titjib fil- punteġġ ACR meta mqabbel mal- pazjenti kkurati b’ methotrexate waħdu (Tabella 7).
The treatment effect was similar in patients independent of rheumatoid factor status, age, gender, body surface area, race, number of prior treatments or disease status.
L- effett tal- kura kien simili fil- pazjenti indipendentement mill- istat tal- fattur rewmatiku, l - età, is- sess tal- persuna, l- arja tas- superfiċje tal- ġisem, ir- razza, in- numru ta ’ trattamenti preċedenti jew l- istat tal- marda.
Clinically and statistically significant improvement was also noted on all individual components of the ACR response (tender and swollen joint counts, patient and physician global assessment, disability index scores (HAQ), pain assessment and C-Reactive Proteins (mg/ dL).
Titjib klinikament u statistikament sinifikanti ġie nnotat ukoll fuq il- komponenti individwali kollha tar- rispons ACR (għadd ta ’ ġogi sensittivi u minfuħin, evalwazzjoni globali mill- pazjent u t- tabib, punteġġi fuq l- indiċi tad- diżabilità (HAQ), evalwazzjoni ta ’ l- uġigħ u Proteini Reattivi għal C (mg/ dL).
Cross-Study Comparison of ACR Responses at Week 24 (ITT Population)
Cross- Study tar- Risponsi ACR fil- Ġimgħa 24 (Popolazzjoni ITT)
ACR Response Placebo+MTX Rituximab+MTX
Rispons Plaċebo+MTX Rituximab+MTX ACR
36 (18%) 11 (5%) 3 (1%) N= 143
19 (13%)
153 (51%)1 80 (27%)1 37 (12%)1 N= 185
28 (15%) 2
Study 3 1
Studju 3
p ≤ 0.0001; p ≤ 0.001; 3 p < 0.05 2
p ≤ 0. 0001; p ≤ 0. 001; 3 p < 0. 05 2
MTX – Methotrexate
MTX – Methotrexate
In study 3, the ACR20 response in patients treated with rituximab alone was 65% compared with 38% on methotrexate alone (p=0.025).
Fi studju 3, ir- rispons ACR20 fil- pazjenti kkurati b’ rituximab waħdu kien ta ’ 65% meta mqabbel mat - 38% fuq methotrexate waħdu (p=0. 025).
23 Rituximab treated patients had a significantly greater reduction in disease activity score (DAS28) than patients treated with methotrexate alone (Mean change in DAS28 from baseline -1.9 vs. -0.4, p < 0.0001, respectively).
24 Il- pazjenti kkurati b’ rituximab kellhom tnaqqis sinifikanti akbar fil- punteġġ ta ’ l- attività tal- marda (DAS28) mill- pazjenti kkurati b’ methotrexate waħdu (Bidla medja fid- DAS28 mil- linja bażika - 1. 9 vs - 0. 4, p < 0. 0001, rispettivament).
A good to moderate European League Against Rheumatism (EULAR) response was achieved by significantly more rituximab treated patients compared to patients treated with methotrexate alone (Table 9).
Rispons European League Against Rheumatism (EULAR) tajjeb għal moderat ġie miksub minn ammont sinifikattivament akbar ta ’ pazjenti kkurati b’ rituximab meta mqabbel mal- pazjenti kkurati b’ methotrexate waħdu (Tabella 9).
Radiographic response In Study 1, conducted in patients with inadequate response or intolerance to one or more TNF inhibitor therapies, structural joint damage was assessed radiographically and expressed as change in modified total Sharp score and its components, the erosion score and joint space narrowing score.
Rispons radjografiku Fi Studju 1, imwettaq f’ pazjenti b’ rispons inadegwat jew intolleranza għal terapija waħda jew aktar ta ’ inibizzjoni TNF, il- ħsara strutturali fil- ġogi ġiet evalwata b’ mod radjografiku u espressa bħala bidla fil- punteġġ Sharp totali modifikat u l- komponenti tiegħu, il- punteġġ tat- tgħawwir u l- punteġġ tat- tidjiq ta ’ l- ispazju bejn il- ġogi.
Patients originally receiving rituximab/ MTX demonstrated significantly less radiographic progression than patients originally receiving methotrexate alone at 56 weeks.
Il- pazjenti li oriġinarjament irċevew rituximab/ MTX urew progressjoni radjografika sinifikattivament anqas mill- pazjenti li oriġinarjament irċevew methotrexate waħdu wara 56 ġimgħa.
Of the patients originally receiving methotrexate alone, 81% received rituximab either as rescue between weeks 16-24 or in the extension trial, before week 56.
Mill- pazjenti li oriġinarjament kienu qegħdin jirċievu methotrexate waħdu, 81% rċevew rituximab jew bħala salvataġġ bejn ġimgħa 16- 24 jew fil- prova ta ’ estensjoni, qabel ġimgħa 56.
A higher proportion of patients receiving the original rituximab/ MTX treatment also had no erosive progression over 56 weeks (Table 8).
Proporzjon akbar ta ’ pazjenti li kienu qegħdin jirċievu l- kura oriġinali b’ rituximab/ MTX ukoll ma kellhom l- ebda progressjoni tat- tgħawwir fuq 56 ġimgħa (Tabella 8).
56 weeks in Study 1
Bidliet radjografiċi medji fuq 56 ġimgħa fi Studju 1
Placebo+MTX
Plaċebo+MTX
Study 1 Total Sharp score
Studju 1 Punteġġ Sharp totali
= 184) 2.31
= 184) 2. 31
= 273) 1.00
= 273) 1. 00
p=0.0046 Erosion Score
p=0. 0046 Punteġġ tat- tgħawwir
0.59
0. 59
p=0.0114 Joint Space narrowing score
p=0. 0114 Punteġġ tat- tidjiq ta ’ l- Ispazju bejn il -
p=0.0006 Proportion of patients with no erosive
Ġogi p=0. 0006 Proporzjon ta ’ pazjenti mingħajr ebda
progression over 56 weeks
p=0. 0494 progressjoni tat- tgħawwir fuq 56 ġimgħa
1.3, respectively, Study 1).
Riżultati tal- kwalità tal- ħajja Kien osservat tnaqqis sinifikanti fl- indiċi tad- diżabilità (HAQ- DI), l- għeja (FACIT- F) (Tabella 9), u titjib kemm fl- oqsma fiżiċi kif ukoll ta ’ saħħa mentali tas- SF- 36 fil- pazjenti kkurati b’ rituximab meta mqabbel mal- pazjenti kkurati b’ methotrexate waħdu (SF- 36 Fiżiku 5. 8 vs 0. 9, SF- 36 Mentali 4. 7 vs 1. 3, rispettivament, Studju 1).
Disease Activity and Quality of Life Outcomes at Week 24 in Study 1
L- Attività tal- Marda u r- Riżultati tal- Kwalità tal- Ħajja fil- Ġimgħa 24 fi Studju 1
Change from baseline
Rispons f’ Ġimgħa 24:
Placebo+MTX1 N= 201 mean (SD)
Valur p
Rituximab+MTX1 N= 298 mean (SD) switch
Bidla mil- linja bażika
p-value
N= 298
EULAR Good/ moderate
EULAR Tajjeb/ moderat
22%
(SD) medja 22%
65%
medja (SD) 65%
HAQ2 3
3
-0.1 (0.5)
- 0. 1 (0. 5)
-0.4 (0.6)
- 0. 4 (0. 6)
-0.5 (9.8) 3
- 0. 5 (9. 8)
-9.1 (11.3)
- 9. 1 (11. 3)
MTX Health assessment questionnaire (HAQ), Functional assessment of chronic illness therapy (FACIT-F)
MTX, 2 Kwestjonarju għall- evalwazzjoni tas- saħħa (HAQ), 3 Evalwazzjoni funzjonali tat- terapija għal mard kroniku (FACIT- F)
At week 24, in all three studies, the proportion of rituximab treated patients showing a clinically relevant improvement in HAQ-DI (defined as an individual total score decrease of > 0.25) was higher than among patients receiving methotrexate alone.
F’ ġimgħa 24, f’ dawn it- tliet studji kollha, il- proporzjon ta ’ pazjenti kkurati b’ rituximab li wrew titjib klinikament sinifikanti fl- HAQ- DI (definit bħala tnaqqis fil- punteġġ totali individwali ta ’ > 0. 25) kien ogħla milli fost il- pazjenti li rċevew methotrexate waħdu.
Laboratory evaluations A total of 96/ 1039 (9.2%) patients with rheumatoid arthritis tested positive for HACA in clinical studies following therapy with MabThera.
25 Evalwazzjonijiet tal- laboratorju Total ta ’ 96/ 1039 (9. 2%) pazjent b’ artrite rewmatika kienu ttestjati pożittivi għal HACA fi studji kliniċi wara terapija b’ MabThera.
The emergence of HACA was not associated with clinical deterioration or with an increased risk of reactions to subsequent infusions in the majority of patients.
It- tfaċċar ta ’ HACA ma kienx assoċjat ma ’ deterjorament kliniku jew ma ’ riskju akbar ta ’ reazzjonijiet għal infużjonijiet suċċessivi fil- maġġoranza tal- pazjenti.
24 The presence of HACA may be associated with worsening of infusion or allergic reactions after the second infusion of subsequent courses.
Il - preżenza ta ’ HACA tista ’ tkun assoċjata mat- taħżin ta ’ reazzjonijiet għall- infużjoni jew allerġiċi wara t- tieni infużjoni ta ’ korsijiet suċċessivi.
Furthermore, in one case with HACA, failure to deplete B cells after receipt of further treatment courses has been observed.
Barraminhekk, f’ każ wieħed b’ HACA, kien osservat falliment li jitnaqqsu ċ- ċelluli B wara r- riċeviment ta ’ aktar korsijiet ta ’ kura.
In 675 patients in clinical studies, the following shifts in anti-nuclear antibody (ANA) status were observed before and after rituximab:
F’ 675 pazjent fi studji kliniċi, kienu osservati l- bidliet li ġejjin fl- istatus ta ’ l- antikorpi antinukleari (ANA) qabel u wara rituximab:
26% ANA negative to positive and 32% ANA positive to negative.
26% ANA negattivi għal pożittivi u 32% ANA pożittivi għal negattivi.
There was no evidence of new onset autoimmune disease.
Ma kien hemm ebda evidenza ta ’ bidu ta ’ mard ġdid awto- immuni.
In rheumatoid factor (RF) positive patients, marked decreases were observed in rheumatoid factor concentrations following treatment with rituximab in all three studies (range 45-64%).
F’ pazjenti pożittivi għall- fattur rewmatiku (RF), kien osservat tnaqqis ċar fil- konċentrazzjonijiet tal - fattur rewmatiku wara kura b’ rituximab fit- tliet studji kolha (medda 45- 64%).
Hyperuricemia (grade 3/ 4) occurred in 143/ 950 (15%) patients, with the majority post-infusion on days 1 and/ or 15.
Iperuriċemija (grad 3/ 4) seħħet f’ 143/ 950 (15%) pazjent, bil- maġġoranza jkunu wara l- infużjoni fl - ewwel u/ jew fil- ħmistax- il jum.
It was not associated with any clinical symptoms, and none of these patients developed evidence of renal disease.
Hija ma kinetx assoċjata ma ’ xi sintomi kliniċi, u ħadd minn dawn il - pazjenti ma żviluppa evidenza ta ’ mard tal- kliewi.
Plasma total immunoglobulin concentrations, total lymphocytes counts, and white cells generally remained within normal limits following MabThera treatment, with the exception of a transient drop in white cells counts over the first four weeks following therapy.
Il- konċentrazzjonijiet globali ta ’ immunoglobulina fil- plasma, l- għadd totali ta ’ limfoċiti, u ċ- ċelluli bojod ġeneralment baqgħu fil- limiti normali wara kura b’ MabThera, bl- eċċezzjoni ta ’ tnaqqis temporanju fl- għadd ta ’ ċelluli bojod matul l- ewwel erba ’ ġimgħat wara t- terapija.
Titers of Ig G antigen specific antibody to mumps, rubella, varicella, tetanus toxoid, influenza and streptococcus pneumococci remained stable over 24 weeks following exposure to MabThera in rheumatoid arthritis patients.
Tajters ta ’ antikorp speċifiku għall- antiġen IgG għall- ħożba, ir- rubella, il- ġidri r- riħ, it- tetanus toxoid, l- influwenza u l - istreptococcus pneumococci baqgħu stabbli fuq 24 ġimgħa wara l- esponiment għal MabThera f’ pazjenti b’ artrite rewmatika.
Multiple course therapy Following completion of the 24-week double blind comparative study period, patients were permitted to enroll into an open-label long term follow up study.
Terapija b’ diversi korsijiet Wara li ntemm il- perijodu ta ’ 24 ġimgħa ta ’ l- istudju komparattiv double- blind, il- pazjenti kienu permessi li jirreġistraw fi studju ta ’ tkomplija tat- tip open- label fuq perijodu fit- tul.
Patients received subsequent courses of MabThera as needed according to the treating clinician’ s assessment of disease activity and irrespective of the peripheral B lymphocyte count.
Il- pazjenti rċevew korsijiet suċċessivi ta ’ MabThera skond l- evalwazzjoni ta ’ l- attività tal- marda mit- tabib kuranti u irrispettivament mill- għadd ta ’ limfoċiti B periferali.
The time interval between courses was variable, with the majority of patients receiving further therapy 6-12 months after the previous course.
L- intervall bejn il- korsijiet kien varjabbli, bil - maġġoranza tal- pazjenti jirċievu aktar terapija 6- 12- il xahar wara l- kors preċedenti.
Some patients required even less frequent retreatment.
Xi pazjenti kellhom bżonn kura mill- ġdid saħansitra anqas ta ’ spiss.
Mean change in DAS28 from original baseline: first course -2.18, second course -2.75.
Ir- rispons għal terapija addizzjonali kien mill - anqas ta ’ l- istess daqs bħal dak ta ’ wara l- kors inizjali tal- kura, kif muri mill- bidla mid- DAS28 tal - linja bażi: l- ewwel kors - 2. 18, it- tieni kors - 2. 75.
non-Hodgkin’ s lymphoma
Limfoma mhux ta ’ Hodgkin
Based on a population pharmacokinetic analysis in 298 NHL patients who received single or multiple infusions of rituximab as a single agent or in combination with CHOP therapy (applied rituximab doses ranged from 100 to 500 mg/ m2), the typical population estimates of nonspecific clearance (CL1), specific clearance (CL2) likely contributed by B cells or tumor burden, and central compartment volume of distribution (V1) were 0.14 L/ day, 0.59 L/ day, and 2.7 L, respectively.
Ibbażat fuq analiżi tal- farmakokinetika tal- popolazzjoni f’ 298 pazjent b’ NHL li rċevew infużjonijiet singoli jew multipli ta ’ rituximab bħala sustanza waħedha jew flimkien ma ’ terapija CHOP (id- dożi ta ’ rituximab applikati varjaw minn 100 sa 500 mg/ m2), l- estimi tipiċi tal- popolazzjoni tat- tneħħija mhux speċifika (CL1), tat- tneħħija speċifika (CL2) probabbli kkontribwita minn ċelluli B jew mill- massa tat - tumur, u tal- volum ta ’ distribuzzjoni tal- kompartiment ċentrali (V1) kienu 0. 14 L/ kuljum, 0. 59 L/ kuljum, u 2. 7 L, rispettivament.
The estimated median terminal elimination half-life of rituximab was 22 days (range, 6.1 to 52 days).
Il- medjan tal- half- life tal- eliminazzjoni terminali stmata ta ’ rituximab kienet 22 ġurnata (firxa, 6. 1 sa 52 ġurnata).
Baseline CD19-positive cell counts and size of measurable tumor lesions contributed to some of the variability in CL2 of rituximab in data from 161 patients given 375 mg/ m2 as an intravenous infusion for 4 weekly doses.
Linja bażi ta ’ l- għadd ta ’ ċelluli pożittivi għal CD19 u tad- daqs ta ’ leżjonijiet tat- tumur li jistgħu jitkejjlu kkontribwixxew għal xi ftit mill- varjabilità fis- CL2 ta ’ rituximab fit- tagħrif minn 161 pazjent mogħtija 375 mg/ m2 bħala infużjoni fil- vini għal 4 dożi fil- ġimgħa.
Patients with higher CD19-positive cell counts or tumor lesions had a higher CL2.
Pazjenti b’ għadd ogħla ta ’ ċelluli pożittivi għal CD19 jew ta ’ feriti tat- tumur kellhom CL2 ogħla.
However, a large component of inter-individual variability remained for CL2 after correction for CD19-positive cell counts and tumor lesion size.
Madankollu wara l- korrezzjoni għall- għadd taċ- ċelluli pożittivi għal CD19 u għad- daqs tal - leżjonijiet tat- tumur, jifdal komponent kbir tal- varjabilità bejn individwu u ieħor għal CL2.
V1 varied by body surface area (BSA) and CHOP therapy.
V1 varja ma ’ l- erja tas- superfiċje tal- ġisem (BSA) u mat- terapija CHOP.
This variability in V1 (27.1% and 19.0%) contributed by the range in BSA (1.53 to 2.32 m2) and concurrent CHOP therapy, respectively, were relatively small.
Din il- varjabilità f’ V1 (27. 1% u 19. 0%) ikkontribwita mill- firxa f’ BSA (1. 53 sa 2. 32 m2) u mit- terapija CHOP fl- istess waqt, rispettivament, kienu relattivament żgħar.
Age, gender and WHO performance status had no effect on the pharmacokinetics of rituximab.
Età, sess, rażża, u WHO performance status ma kellhom l - ebda effett fuq il- farmakokinetika ta ’ rituximab.
This analysis suggests that dose adjustment of rituximab with any of the tested covariates is not expected to result in a meaningful reduction in its pharmacokinetic variability.
26 rituximab ma ’ kull ko- varjabbli ttestjat mhux mistenni li jirriżulta fi tnaqqis sinifikanti fil- varjabilità tal- farmakokinetika tiegħu.
Rituximab, administered as an intravenous infusion at a dose of 375 mg/ m2 at weekly intervals for 4 doses to 203 patients with NHL naive to rituximab, yielded a mean Cmax following the fourth infusion of 486 µg/ mL (range, 77.5 to 996.6 µg/ mL).
Rituximab mogħti f’ doża ta ’ 375 mg/ m2 bħala infużjoni fil- vini f’ intervalli ta ’ kull ġimgħa għal 4 dożi lil 203 pazjent b’ NHL li qatt ma kienu ħadu rituximab qabel, ipproduċa Cmax medja wara r- raba ’ infużjoni ta ’ 486 µg/ mL (firxa, 77. 5 sa 996. 6 µg/ mL).
Rituximab was detectable in the serum of patients 3 – 6 months after completion of last treatment.
Rituximab kien osservat fis- serum ta ’ pazjenti 3 – 6 xhur wara t- tmiem ta ’ l- aħħar kura.
25 Upon administration of rituximab at a dose of 375 mg/ m2 as an intravenous infusion at weekly intervals for 8 doses to 37 patients with NHL, the mean Cmax increased with each successive infusion, spanning from a mean of 243 µg/ mL (range, 16 – 582 µg/ mL) after the first infusion to 550 µg/ mL (range, 171 – 1177 µg/ mL) after the eighth infusion.
Ma l- għoti ta ’ Rituximab f’ doża ta ’ 375 mg/ m2 bħala infużjoni fil- vini f’ intervalli ta ’ kull ġimgħa għal 8 dożi lil 37 pazjent b’ NHL, Cmax medja żdiedet ma ’ kull infużjoni ta ’ wara, varjat minn medja ta ’ 243 µg/ mL (firxa, 16 – 582 µg/ mL) wara l- ewwel infużjoni għal 550 µg/ mL (firxa, 171 – 1177 µg/ mL) wara t- tmin infużjoni.
The pharmacokinetic profile of rituximab when administered as 6 infusions of 375 mg/ m2 in combination with 6 cycles of CHOP chemotherapy was similar to that seen with rituximab alone.
Il- profil farmakokinetiku ta ’ rituximab meta mogħti bħala 6 infużjonijiet ta ’ 375 mg/ m2 flimkien ma ’ 6 ċikli ta ’ kimoterpija CHOP kien simili għal dak li deher b’ rituximab waħdu.
Following two intravenous infusions of rituximab at a dose of 1000 mg, two weeks apart, the mean terminal half-life was 20.8 days (range, 8.58 to 35.9 days), mean systemic clearance was 0.23 L/ day (range, 0.091 to 0.67 L/ day), and mean steady-state distribution volume was 4.6 L (range, 1.7 to 7.51 L).
Wara żewġ infużjonijiet ġol- vina ta ’ rituximab f’ doża ta ’ 1000 mg, ġimagħtejn ’ il bogħod minn xulxin, il- medja tal- half- life terminali kienet ta ’ 20. 8 ġurnata (medda, 8. 58 sa 35. 9 ġurnata), il- medja tat - tneħħija sistemika kienet ta ’ 0. 23 L/ kuljum (medda, 0. 091 sa 0. 67 L/ kuljum), u l- medja tal- volum tad - distribuzzjoni fiss kienet ta ’ 4. 6 L (medda, 1. 7 sa 7. 51 L).
Population pharmacokinetic analysis of the same data gave similar mean values for systemic clearance and half-life, 0.26 L/ day and 20.4 days, respectively.
L- analiżi farmakokinetika fuq il - popolazzjoni ta ’ l- istess informazzjoni tat valuri medji simili għat- tneħħija sistemika u l- half- life, 0. 26 L/ kuljum u 20. 4 ġurnata, rispettivament.
Population pharmacokinetic analysis revealed that BSA and gender were the most significant covariates to explain inter-individual variability in pharmacokinetic parameters.
L- analiżi farmakokinetika fuq il- popolazzjoni wriet li l- BSA u s- sess tal- persuna kienu l- aktar covariates sinifikanti biex tiġi spjegata l- varjabilità fil- parametri farmakokinetiċi bejn l- individwi.
After adjusting for BSA, male subjects had a larger volume of distribution and a faster clearance than female subjects.
Wara l- aġġustament għall- BSA, is- suġġetti rġiel kellhom volum akbar ta ’ distribuzzjoni u tneħħija aktar veloċi mis- suġġetti nisa.
The gender- related pharmacokinetic differences are not considered to be clinically relevant and dose adjustment is not required.
Id- differenzi farmakokinetiċi relatati mas- sess tal- persuna mhumiex meqjusa ta ’ rilevanza klinika u mhuwiex meħtieġ aġġustament fid- doża.
Following the intravenous administration of 500 and 1000 mg doses of rituximab on two occasions, two weeks apart, mean Cmax values were 183 μ g/ mL (range, 81.8 to 279 μ g/ mL) and 370 μ g/ mL (212 to 637 μ g/ mL), and mean half-lives were 17.9 days (range, 12.3 to 31.3 days) and 19.7 days (range, 12.3 to 34.6 days), respectively.
Wara l- għoti minn ġol- vini ta ’ dożi ta ’ 500 u 1000 mg ta ’ rituximab f’ żewġ okkażjonijiet, ġimagħtejn ’ il bogħod minn xulxin, il- medja tal- valuri Cmax kienet ta ’ 183 μg/ mL (medda, 81. 8 sa 279 μg/ mL) u 370 μg/ mL (212 sa 637 μg/ mL), u l- medja tal- half- lives kienet ta ’ 17. 9- il ġurnata (medda, 12. 3 sa 31. 3 ġurnata) u 19. 7- il ġurnata (medda, 12. 3 sa 34. 6 ġurnata), rispettivament.
No pharmacokinetic data are available in patients with hepatic or renal impairment.
Ma hija disponibbli l- ebda informazzjoni farmakokinetika għal pazjenti b’ indeboliment tal- fwied jew tal - kliewi.
No pharmacokinetic data are available for patients receiving multiple courses of therapy.
Ma hija disponibbli l- ebda informazzjoni farmakokinetika għall- pazjenti li rċevew diversi korsijiet ta ’ terapija.
The pharmacokinetic (PK) parameters in the anti-TNF inadequate responder population, following the same dosage regimen (2 x 1000 mg, iv, 2 weeks apart), were similar with a mean maximum serum concentration of 369 μ g/ mL and a mean terminal half-life of 19.2 days.
Il- parametri farmakokinetiċi (PK) fil- popolazzjoni li rrispondiet b’ mod inadegwat għall- mediċini kontra TNF, bl- użu ta ’ l- istess reġim ta ’ dożaġġ (2 x 1000 mg, iv, ġimagħtejn ’ il bogħod minn xulxin), kienu simili b’ konċentrazzjoni massima medja fis- serum ta ’ 369 μg/ mL u half - life terminali medja ta ’ 19. 2- il ġurnata.
Rituximab has shown to be highly specific to the CD20 antigen on B cells.
Rituximab wera li huwa speċifiku ħafna għall- antiġen CD20 fuq iċ- ċelluli B.