In the phase 3 LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered or ineligible for transplant, the median progression-free survival was significantly improved with VR-CAP (24.7versus14.4 months with R-CHOP;P<0.001). Thispost-hocanalysis evaluated the association between the improved outcomes and quality of responses achieved with VR-CAPversusR-CHOP in LYM-3002. Patients were randomized to six to eight 21-day cycles of VR-CAP or R-CHOP. Outcomes included progression-free survival, duration of response (both assessed by an independent review committee), and time to next anti-lymphoma treatment, evaluated by response (complete response/unconfirmed complete response and partial response), MIPI risk status, and maximum reduction of lymph-node measurements expressed as the sum of the product of the diameters. Within each response category, the median progression-free survival was longer for patients given VR-CAP than for those given R-CHOP (complete response/unconfirmed complete response: 40.9versus19.8 months; partial response: 17.1versus11.7 months, respectively); similarly, the median time to next anti-lymphoma treatment was longer among the patients given VR-CAP than among those treated with R-CHOP (complete response/unconfirmed complete response: not evaluableversus26.6 months; partial response: 35.3versus24.3 months). Within the complete/unconfirmed complete and partial response categories, improvements in progression-free survival, duration of response and time to next anti-lymphoma treatment were more pronounced in patients with low-and intermediate-risk MIPI treated with VR-CAP than with R-CHOP. In each response category, more VR-CAP than R-CHOP patients had a sum of the product of the diameters nadir of 0 during serial radiological assessments. Results of thispost-hocanalysis suggest a greater duration and quality of response in patients treated with VR-CAP in comparison with those treated with R-CHOP, with the improvements being more evident in patients with low- and intermediate-risk MIPI.LYM-3002 ClinicalTrials.gov: NCT00722137.

• MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• indukce remise MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk farmakoterapie   patologie   MeSH
• myší monoklonální protilátky aplikace a dávkování   MeSH
• prednison aplikace a dávkování   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• rituximab aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. METHODS: LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed. FINDINGS: Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1-94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51-0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. INTERPRETATIONS: Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma. FUNDING: Janssen Research & Development.

• MeSH
• bortezomib aplikace a dávkování   škodlivé účinky   MeSH
• časové faktory MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• doba přežití bez progrese choroby MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk farmakoterapie   mortalita   patologie   MeSH
• myší monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• progrese nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři MeSH
• staging nádorů MeSH
• vinkristin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Severní Amerika MeSH

The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m2/cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m2/cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

• MeSH
• analýza přežití MeSH
• bortezomib aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk farmakoterapie   mortalita   MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH