BACKGROUND: Lurbinectedin is a synthetic marine-derived anticancer agent that acts as a selective inhibitor of oncogenic transcription. Lurbinectedin monotherapy (3·2 mg/m2 every 3 weeks) received accelerated approval from the US Food and Drug Administration on the basis of efficacy in patients with small-cell lung cancer (SCLC) who relapsed after first-line platinum-based chemotherapy. The ATLANTIS trial assessed the efficacy and safety of combination lurbinectedin and the anthracycline doxorubicin as second-line treatment for SCLC. METHODS: In this phase 3, open-label, randomised study, adult patients aged 18 years or older with SCLC who relapsed after platinum-based chemotherapy were recruited from 135 hospitals across North America, South America, Europe, and the Middle East. Patients were randomly assigned (1:1) centrally by dynamic allocation to intravenous lurbinectedin 2·0 mg/m2 plus doxorubicin 40·0 mg/m2 administered on day 1 of 21-day cycles or physician's choice of control therapy (intravenous topotecan 1·5 mg/m2 on days 1-5 of 21-day cycles; or intravenous cyclophosphamide 1000 mg/m2, doxorubicin 45·0 mg/m2, and vincristine 2·0 mg on day 1 of 21-day cycles [CAV]) administered until disease progression or unacceptable toxicity. Primary granulocyte-colony stimulating factor prophylaxis was mandatory in both treatment groups. Neither patients nor clinicians were masked to treatment allocation, but the independent review committee, which assessed outcomes, was masked to patients' treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02566993, and with EudraCT, 2015-001641-89, and is complete. FINDINGS: Between Aug 30, 2016, and Aug 20, 2018, 613 patients were randomly assigned to lurbinectedin plus doxorubicin (n=307) or control (topotecan, n=127; CAV, n=179) and comprised the intention-to-treat population; safety endpoints were assessed in patients who had received any partial or complete study treatment infusions (lurbinectedin plus doxorubicin, n=303; control, n=289). After a median follow-up of 24·1 months (95% CI 21·7-26·3), 303 patients in the lurbinectedin plus doxorubicin group and 289 patients in the control group had discontinued study treatment; progressive disease was the most common reason for discontinuation (213 [70%] patients in the lurbinectedin plus doxorubicin group vs 152 [53%] in the control group). Median overall survival was 8·6 months (95% CI 7·1-9·4) in the lurbinectedin plus doxorubicin group versus 7·6 months (6·6-8·2) in the control group (stratified log-rank p=0·90; hazard ratio 0·97 [95% CI 0·82-1·15], p=0·70). 12 patients died because of treatment-related adverse events: two (<1%) of 303 in the lurbinectedin plus doxorubicin group and ten (3%) of 289 in the control group. 296 (98%) of 303 patients in the lurbinectedin plus doxorubicin group had treatment-emergent adverse events compared with 284 (98%) of 289 patients in the control group; treatment-related adverse events occurred in 268 (88%) patients in the lurbinectedin plus doxorubicin group and 266 (92%) patients in the control group. Grade 3 or worse haematological adverse events were less frequent in the lurbinectedin plus doxorubicin group than the control group (anaemia, 57 [19%] of 302 patients in the lurbinectedin plus doxorubicin group vs 110 [38%] of 288 in the control group; neutropenia, 112 [37%] vs 200 [69%]; thrombocytopenia, 42 [14%] vs 90 [31%]). The frequency of treatment-related adverse events leading to treatment discontinuation was lower in the lurbinectedin plus doxorubicin group than in the control group (26 [9%] of 303 patients in the lurbinectedin plus doxorubicin group vs 47 [16%] of 289 in the control group). INTERPRETATION: Combination therapy with lurbinectedin plus doxorubicin did not improve overall survival versus control in patients with relapsed SCLC. However, lurbinectedin plus doxorubicin showed a favourable haematological safety profile compared with control. FUNDING: PharmaMar.

• MeSH
• dospělí MeSH
• doxorubicin škodlivé účinky   MeSH
• lékaři * MeSH
• lidé MeSH
• nádory plic * etiologie   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• topotekan terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Anti-CD19 immunotherapy tafasitamab is used in combination with lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Open-label, phase 1b, First-MIND study assessed safety and preliminary efficacy of tafasitamab + R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) ± lenalidomide as first-line therapy in patients with DLBCL. From December 2019 to August 2020, 83 adults with untreated DLBCL (International Prognostic Index 2-5) were screened and 66 were randomly assigned (33 per arm) to R-CHOP-tafasitamab (arm T) or R-CHOP-tafasitamab-lenalidomide (arm T/L) for 6 cycles. Primary end point was safety; secondary end points included end-of-treatment (EoT) overall response rate (ORR) and complete response (CR) rate. All patients had ≥1 treatment-emergent adverse event, mostly grade 1 or 2. Grade ≥3 neutropenia and thrombocytopenia occurred, respectively, in 57.6% and 12.1% (arm T) and 84.8% and 36.4% (arm T/L) of patients. Nonhematologic toxicities occurred at similar rates among arms. R-CHOP mean relative dose intensity was ≥89% in both arms. EoT ORR was 75.8% (CR 72.7%) in arm T and 81.8% (CR 66.7%) in arm T/L; best ORR across visits was 90.0% and 93.9%. Eighteen-month duration of response and of CR rates were 72.7% and 74.5% (arm T) and 78.7% and 86.5% (arm T/L); 24-month progression-free and overall survival rates were 72.7% and 90.3% (arm T) and 76.8% and 93.8% (arm T/L). Manageable safety and promising signals of efficacy were observed in both arms. Potential benefit of adding tafasitamab + lenalidomide to R-CHOP is being investigated in phase 3 frontMIND (NCT04824092). This study is registered at www.clinicaltrials.gov as #NCT04134936.

• MeSH
• cyklofosfamid škodlivé účinky   MeSH
• difúzní velkobuněčný B-lymfom * patologie   MeSH
• dospělí MeSH
• doxorubicin škodlivé účinky   MeSH
• lenalidomid terapeutické užití   MeSH
• lidé MeSH
• myší monoklonální protilátky škodlivé účinky   MeSH
• prednison škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• rituximab škodlivé účinky   MeSH
• vinkristin škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. METHODS: We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety. RESULTS: Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P = 0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was similar in the two groups. CONCLUSIONS: Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.).

• MeSH
• cyklofosfamid škodlivé účinky   terapeutické užití   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   mortalita   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doxorubicin škodlivé účinky   terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• imunokonjugáty aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• prednison škodlivé účinky   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• rituximab škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• vinkristin škodlivé účinky   terapeutické užití   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
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

CONTEXT: R-CHOP is the standard of care for newly diagnosed DLBCL patients; however, 40% remain uncured. Polatuzumab vedotin (Pola), a CD79b-targeting antibody-drug conjugate, has shown promising activity/safety in a Phase Ib/II study (Tilly, et al. Lancet Oncol 2019). We report the Phase III double-blind, placebo-controlled, international POLARIX study (NCT03274492), which compared Pola-R-CHP with R-CHOP in treatment-naïve DLBCL patients with an International Prognostic Index score of 2-5. DESIGN: Patients were randomized (1:1) to six cycles of Pola-R-CHP or R-CHOP and on Day 1 of each cycle received Pola 1.8mg/kg or vincristine 1.4mg/m2, plus intravenous rituximab 375mg/m2, cyclophosphamide 750mg/m2, and doxorubicin 50mg/m2. Patients also received oral prednisone 100mg once daily (Days 1-5) and two further cycles of rituximab. The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: Overall, 879 patients (median age 65 [range 19-80] years) were randomized (Pola-R-CHP: n=440; R-CHOP: n=439). At primary data cut-off (28 June 2021), median follow-up was 28.2 months. PFS was superior with Pola-R-CHP vs R-CHOP (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57-0.95; P=0.02) and 2-year PFS rate was improved (76.7% [95% CI: 72.7-80.8] vs 70.2% [95% CI: 65.8-74.6], respectively). Investigator-assessed event-free survival favored Pola-R-CHP vs R-CHOP (HR 0.75; 95% CI: 0.58-0.96; P=0.02) and overall survival was comparable (HR 0.94; 95% CI: 0.65-1.37; P=0.75). While independent review committee-assessed end-of-treatment complete response rate by positron emission tomography-computed tomography was not significantly different with Pola-R-CHP (78.0%) vs R-CHOP (74.0%; P=0.16), disease-free survival suggested more durable responses with Pola-R-CHP vs R-CHOP (HR 0.70; 95% CI: 0.50-0.98). Safety profiles were similar for Pola-R-CHP vs R-CHOP: grade 3-4 adverse event (AE) rates, 57.7% vs 57.5%, respectively; serious AEs, 34.0% vs 30.6%; grade 5 AEs, 3.0% vs 2.3%; AEs leading to dose reduction, 9.2% vs 13.0%; and peripheral neuropathy, any grade, 52.9% vs 53.9%. At data cut-off, fewer patients treated with Pola-R-CHP (23%) vs R-CHOP (30%) had received ≥1 subsequent anti-lymphoma therapy. CONCLUSIONS: As the first-line treatment of DLBCL, Pola-R-CHP demonstrated a 27% reduction in the relative risk of disease progression, relapse, or death, and a similar safety profile, compared with R-CHOP.

• MeSH
• cyklofosfamid škodlivé účinky   MeSH
• difúzní velkobuněčný B-lymfom * terapie   MeSH
• dospělí MeSH
• doxorubicin škodlivé účinky   MeSH
• imunokonjugáty * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• mladý dospělý MeSH
• monoklonální protilátky MeSH
• prednison škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• rituximab terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vinkristin škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

CONTEXT: The chemo-free immunotherapy tafasitamab + lenalidomide (LEN), has received accelerated approval in the United States (2020) and conditional marketing authorization in Europe and Canada (2021) for treatment of relapsed/refractory diffuse large cell lymphoma (DLBCL), in patients ineligible for autologous stem cell transplant. The primary analysis of First-MIND (NCT04134936) demonstrated that adding tafasitamab + LEN does not impair dosing and scheduling of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and toxicities were similar to those expected with R-CHOP alone (ASH 2021; #3556). OBJECTIVE: frontMIND (NCT04824092) will investigate the efficacy and safety of R-CHOP + tafasitamab + LEN versus R-CHOP alone in previously untreated patients with high-intermediate and high-risk DLBCL. DESIGN: A Phase III, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Approximately 350 centers from the Americas, Europe, and the Asia-Pacific region. PATIENTS: Eligible patients (n=880) will be aged 18-80 years with previously untreated local biopsy-proven, CD20-positive DLBCL, International Prognostic Index (IPI) score 3-5 (age-adjusted IPI 2-3 if ≤60 years), and ECOG performance score 0-2. Patients with transformed lymphoma are excluded. INTERVENTIONS: Patients will be randomized 1:1 to receive six 21-day cycles of either R-CHOP + tafasitamab (12 mg/kg intravenously, Days 1, 8, and 15) + LEN (25 mg orally, Days 1-10) or R-CHOP + tafasitamab + LEN placebos. MAIN OUTCOME MEASURES: The primary endpoint is investigator-assessed progression-free survival; secondary endpoints include event-free survival, overall survival, and safety. Minimal residual disease parameters will also be investigated. RESULTS: Results for this study are not yet available. CONCLUSIONS: There remains a high unmet need to improve treatment options for newly diagnosed patients with high-intermediate and high-risk DLBCL. The combination of tafasitamab + LEN + R-CHOP may have synergistic potential. Preliminary data from the First-MIND study suggest that tafasitamab ± LEN + R-CHOP may be tolerable in patients with treatment-naïve DLBCL. frontMIND will provide further evaluation of clinical benefits and safety in patients with newly diagnosed high-intermediate and high-risk DLBCL. The study is funded by MorphoSys AG and conducted with the scientific support of members of the Fondazione Italiana Linfomi and the German Lymphoma Alliance.

• MeSH
• cyklofosfamid farmakologie   terapeutické užití   MeSH
• difúzní velkobuněčný B-lymfom * diagnóza   farmakoterapie   MeSH
• doxorubicin škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky MeSH
• lenalidomid farmakologie   terapeutické užití   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• myší monoklonální protilátky terapeutické užití   MeSH
• nehodgkinský lymfom * farmakoterapie   MeSH
• prednison farmakologie   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• rituximab farmakologie   terapeutické užití   MeSH
• vinkristin škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas, the majority of which have high relapse rates following standard therapy. Despite use of consolidative stem cell transplant (SCT) following frontline therapy, there remains no consensus on its utility. The double-blind randomized phase 3 ECHELON-2 study (#NCT01777152; clinicaltrials.gov) demonstrated improved progression-free survival (PFS) and overall survival with frontline brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP). Herein, we conducted an exploratory subgroups analysis of the impact of consolidative SCT on PFS in patients with previously untreated CD30+ PTCL (ALK- anaplastic large cell lymphoma [ALCL] and non-ALCL) who were in complete response (CR) after frontline treatment with A+CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone. Median PFS follow-up was 47.57 months. The PFS hazard ratio was 0.36, equating to a 64% reduction in the risk of a PFS event in patients who underwent SCT. The median PFS in patients who underwent SCT was not reached, vs 55.66 months in patients who did not undergo SCT. PFS results favored the use of SCT in both ALK- ALCL and non-ALCL subgroups. These data support the consideration of consolidative SCT in patients with CD30+PTCL who achieve CR following treatment with A+CHP.

• MeSH
• anaplastický velkobuněčný lymfom * chemicky indukované   terapie   MeSH
• antigen Ki-1 MeSH
• brentuximab vedotin MeSH
• cyklofosfamid škodlivé účinky   MeSH
• doxorubicin škodlivé účinky   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• prednison škodlivé účinky   MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• vinkristin škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH

The aim of the present study was to perform kidney messenger ribonucleic acid (mRNA) analysis in normotensive, Hannover Sprague-Dawley (HanSD) rats and hypertensive, Ren-2 renin transgenic rats (TGR) after doxorubicin-induced heart failure (HF) with specific focus on genes that are implicated in the pathophysiology of HF-associated cardiorenal syndrome. We found that in both strains renin and angiotensin-converting enzyme mRNA expressions were upregulated indicating that the vasoconstrictor axis of the renin-angiotensin system was activated. We found that pre-proendothelin-1, endothelin-converting enzyme type 1 and endothelin type A receptor mRNA expressions were upregulated in HanSD rats, but not in TGR, suggesting the activation of endothelin system in HanSD rats, but not in TGR. We found that mRNA expression of cytochrome P-450 subfamily 2C23 was downregulated in TGR and not in HanSD rats, suggesting the deficiency in the intrarenal cytochrome P450-dependent pathway of arachidonic acid metabolism in TGR. These results should be the basis for future studies evaluating the pathophysiology of cardiorenal syndrome secondary to chemotherapy-induced HF in order to potentially develop new therapeutic approaches.

• MeSH
• antibiotika antitumorózní škodlivé účinky   MeSH
• doxorubicin škodlivé účinky   MeSH
• hypertenze komplikace   genetika   patofyziologie   MeSH
• krysa rodu rattus MeSH
• ledviny účinky léků   patofyziologie   MeSH
• messenger RNA genetika   MeSH
• nemoci ledvin chemicky indukované   genetika   patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• regulace genové exprese účinky léků   MeSH
• renin-angiotensin systém účinky léků   MeSH
• renin genetika   MeSH
• srdeční selhání chemicky indukované   genetika   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL. The goal of the global, phase III ROBUST study was to compare lenalidomide plus R-CHOP (R2-CHOP) with placebo/R-CHOP in previously untreated, ABC-type DLBCL. METHODS: Histology and cell-of-origin type were prospectively analyzed by central pathology prior to random assignment and study treatment. Patients with ABC-DLBCL received lenalidomide oral 15 mg/d, days 1-14/21 plus standard R-CHOP21 versus placebo/R-CHOP21 for six cycles. The primary end point was progression-free survival (PFS) per independent central radiology review. RESULTS: A total of 570 patients with ABC-DLBCL (n = 285 per arm) were stratified by International Prognostic Index score, age, and bulky disease, and randomly assigned to R2-CHOP or placebo/R-CHOP. Baseline demographics were similar between arms. Most patients completed six cycles of treatment: 74% R2-CHOP and 84% placebo/R-CHOP. The most common grade 3/4 adverse events for R2-CHOP versus placebo/R-CHOP were neutropenia (60% v 48%), anemia (22% v 14%), thrombocytopenia (17% v 11%), and leukopenia (14% v 15%). The primary end point of PFS was not met, with a hazard ratio of 0.85 (95% CI, 0.63 to 1.14) and P = .29; median PFS has not been reached for either arm. PFS trends favoring R2-CHOP over placebo/R-CHOP were seen in patients with higher-risk disease. CONCLUSION: ROBUST is the first DLBCL phase III study to integrate biomarker-driven identification of eligible ABC patients. Although the ROBUST trial did not meet the primary end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.

• MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   mortalita   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   MeSH
• lenalidomid aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles. Primary end points were safety, tolerability, and research_plete response (CR) at end of treatment (EOT). Secondary end points were progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC+ subgroups. With a median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC+ subgroups (HR, 0.55; 95% CI, 0.34-0.89) vs R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI vs GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased, but manageable, myelosuppression and the potential of improved efficacy, particularly in high-risk Bcl-2 IHC+ patient subgroups.

• MeSH
• bicyklické sloučeniny heterocyklické aplikace a dávkování   škodlivé účinky   MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   genetika   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   MeSH
• faktor stimulující kolonie granulocytů terapeutické užití   MeSH
• gastrointestinální nemoci chemicky indukované   MeSH
• geny bcl-2 MeSH
• infekce etiologie   MeSH
• Kaplanův-Meierův odhad MeSH
• krevní nemoci chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové proteiny antagonisté a inhibitory   MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protoonkogenní proteiny c-bcl-2 antagonisté a inhibitory   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sulfonamidy aplikace a dávkování   škodlivé účinky   MeSH
• únava chemicky indukované   MeSH
• vinkristin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• antracykliny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• difúzní velkobuněčný B-lymfom * farmakoterapie   MeSH
• doxorubicin * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kardiotoxicita etiologie   prevence a kontrola   MeSH
• kardiovaskulární nemoci komplikace   MeSH
• klinické zkoušky jako téma MeSH
• kombinovaná farmakoterapie MeSH
• komorbidita MeSH
• lidé MeSH
• nehodgkinský lymfom farmakoterapie   MeSH
• Check Tag
• lidé MeSH