In the pre-novel agent era, the median postprogression overall survival (PPS) of patients with classic Hodgkin lymphoma (cHL) who progress after autologous stem cell transplant (ASCT) was 2 to 3 years. Recently, checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved the depth and durability of response in this population. Here, we report the estimate of PPS in patients with relapsed cHL after ASCT in the era of CPI and BV. In this multicenter retrospective study of 15 participating institutions, adult patients with relapsed cHL after ASCT were included. Study objective was postprogression overall survival (PPS), defined as the time from posttransplant progression to death or last follow-up. Of 1158 patients who underwent ASCT, 367 had progressive disease. Median age was 34 years (range, 27-46) and 192 were male. Median PPS was 114.57 months (95% confidence interval [CI], 91-not achieved) or 9.5 years. In multivariate analysis, increasing age, progression within 6 months, and pre-ASCT positive positron emission tomography scan were associated with inferior PPS. When adjusted for these features, patients who received CPI, but not BV, as first treatment for post-ASCT progression had significantly higher PPS than the no CPI/no BV group (hazard ratio, 3.5; 95% CI, 1.6-7.8; P = .001). Receipt of allogeneic SCT (Allo-SCT) did not improve PPS. In the era of novel agents, progressive cHL after ASCT had long survival that compares favorably with previous reports. Patients who receive CPI as first treatment for progression had higher PPS. Receipt to Allo-SCT was not associated with PPS in this population.

• MeSH
• brentuximab vedotin MeSH
• dospělí MeSH
• Hodgkinova nemoc * terapie   MeSH
• imunokonjugáty * MeSH
• kojenec MeSH
• lidé MeSH
• retrospektivní studie MeSH
• transplantace kmenových buněk MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická 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

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

CONTEXT: The chemo-free immunotherapy tafasitamab + lenalidomide was granted accelerated approval in the United States (2020) and conditional approval in Canada and Europe (2021) for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in autologous stem cell transplant-ineligible adult patients. We report pharmacokinetics, pharmacodynamics, and immunogenicity in patients with newly diagnosed DLBCL after adding tafasitamab ± lenalidomide to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment. OBJECTIVE: To study the pharmacokinetics, pharmacodynamics, and immunogenicity of tafasitamab. DESIGN: Open-label, randomized, multicenter. SETTING: Fifty sites in North America and Europe. PATIENTS: Eligible patients were ≥18 years with treatment-naïve DLBCL, IPI 2-5, and ECOG PS 0-2. INTERVENTIONS: Patients were randomized 1:1 to six 21-day (D) cycles (C) of either R-CHOP (R-CHO, D1; P, D1-5) + tafasitamab (12 mg/kg IV, D1, 8, 15) (Arm A) or R-CHOP + tafasitamab + lenalidomide (25 mg orally, D1-10) (Arm B). OUTCOME MEASURES: Tafasitamab serum concentration and the number and percentage of patients developing anti-tafasitamab antibodies were secondary endpoints. NK-cell, T-cell, and B-cell counts in peripheral blood were exploratory endpoints. RESULTS: Tafasitamab serum concentrations reached steady state by C3 (geometric mean trough concentrations: Arm A, 186.40-216.55 μg/mL; Arm B, 171.77-201.54 μg/mL) and steadily declined after treatment completion. Anti-tafasitamab antibodies were detected in 1/65 (1.5%) patients and decreased during treatment. Median NK-cell counts decreased from baseline at C1D8 but were at baseline or higher levels by end-of-treatment (EoT) visit (Arm A) and C1D15 (Arm B). T-cell counts decreased from baseline at C1D8 in both arms but were at baseline or higher by C1D15 (Arm A) and EoT visit (Arm B). Median B-cell counts decreased from baseline to 0 cells/μL (Arm A, C1D15; Arm B, C1D8); at 6-month follow-up after EoT visit, B-cell counts recovered to measurable levels in ~50% of patients. CONCLUSIONS: Tafasitamab serum concentration reached and maintained a therapeutic dose level and declined after treatment completion. No patients developed treatment-induced or treatment-boosted anti-tafasitamab antibodies. Median cell counts for NK cells, T cells, and B cells were comparable between treatment arms in all cycles. FUNDING: MorphoSys AG.

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

PURPOSE: Patients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab. METHODS: A phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review. RESULTS: A total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively. CONCLUSION: Lenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile.

• MeSH
• dospělí MeSH
• folikulární lymfom farmakoterapie   MeSH
• lenalidomid aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• lymfom z B-buněk marginální zóny farmakoterapie   MeSH
• placeba MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• rituximab škodlivé účinky   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři 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
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

• MeSH
• alely MeSH
• celogenomová asociační studie * MeSH
• folikulární lymfom genetika   MeSH
• genetická predispozice k nemoci * MeSH
• haplotypy genetika   MeSH
• HLA antigeny genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• lidské chromozomy genetika   MeSH
• nádorové biomarkery genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Intramural MeSH
• srovnávací studie MeSH

• Publikační typ
• abstrakty MeSH