CONTEXT: Camidanlumab tesirine (Cami), an antibody-drug conjugate comprising a human IgG1 anti-CD25 monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer, displayed antitumor activity and manageable toxicity in a phase 1 trial in lymphoma, including R/R cHL (NCT02432235). OBJECTIVE: Present updated efficacy and safety data from a phase 2 study of Cami monotherapy in R/R cHL (NCT04052997). METHODS: Patients with R/R cHL and ≥3 prior systemic therapies including brentuximab vedotin and anti-PD-1 were enrolled. PRIMARY ENDPOINT: overall response rate (ORR). Patients received Cami 45 μg/kg on Day 1 of each 3-week cycle (2 cycles), then 30 μg/kg (subsequent cycles) for up to 1 year. RESULTS: Enrollment is complete (N=117). Median age was 37 years, 62% of patients were male, and 95% had an ECOG score of 0-1. Fourteen patients (12.0%) withdrew to undergo transplant (12 [10.3%] received transplant and were censored). In the all-treated population (N=117), ORR was 70.1% (82/117; 95% CI: 60.9-78.2); 33.3% (39/117) had complete response (CR). At median (range) follow-up of 10.7 (1.2-25.2+) months, the median (95% CI) duration of response (DOR) was 13.7 months (7.4-14.7) for all responders, 14.5 (7.4-not reached, NR) months and 7.9 (3.8-NR) months for patients with CR or PR. Median (95% CI) progression-free survival (PFS) was 9.1 (5.1-15.0) months. All-grade treatment-emergent AEs (TEAEs) in ≥25% of 117 patients were fatigue (38.5%), maculopapular rash (MR, 32.5%), pyrexia (29.9%), nausea (27.4%), and rash (26.5%). Grade ≥3 TEAEs in ≥5% of patients were thrombocytopenia (9.4%), anemia (8.5%), hypophosphatemia (7.7%), neutropenia (7.7%), MR (6.8%), and lymphopenia (5.1%). TEAEs considered immune-related (IR) occurred in 32.5% of patients; Grade ≥3 IR AEs (TEAEs and non-TEAEs; 8.5%). Guillain-Barré syndrome (GBS)/polyradiculopathy occurred in 8 patients (6.8%). At data cutoff, 4 cases had recovered (grade 2, n=2; grade 4, n=2); 4 had not recovered (grade 4, n=1; grade 3, n=3). CONCLUSIONS: Cami demonstrated an ORR of 70.1% (CR: 33.3%) with an encouraging median DOR of 13.7 months and median PFS of 9.1 months. Safety is consistent with prior findings, including similar incidence rates of GBS/polyradiculopathy. Abstract accepted/presented at the EHA 2022 Congress; Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group.

• MeSH
• brentuximab vedotin MeSH
• dospělí MeSH
• exantém * chemicky indukované   farmakoterapie   MeSH
• Hodgkinova nemoc * farmakoterapie   patologie   MeSH
• imunoglobulin G MeSH
• imunokonjugáty * škodlivé účinky   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• polyradikulopatie * chemicky indukované   farmakoterapie   MeSH
• protinádorové látky * terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická 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

BACKGROUND: Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas. METHODS: ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m2 and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152. FINDINGS: Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2-not evaluable) in the A+CHP group and 20·8 months (12·7-47·6) in the CHOP group (hazard ratio 0·71 [95% CI 0·54-0·93], p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group. INTERPRETATION: Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile. FUNDING: Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.

• MeSH
• analýza podle původního léčebného záměru MeSH
• anaplastický velkobuněčný lymfom farmakoterapie   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• imunokonjugáty aplikace a dávkování   škodlivé účinky   MeSH
• imunologické faktory aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prednison aplikace a dávkování   MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   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
• Research Support, N.I.H., Extramural MeSH

Single-agent dacetuzumab has demonstrated antitumor activity in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Preclinical data demonstrated improved dacetuzumab antitumor activity in combination with rituximab, ± chemotherapy. We designed a phase 2b, double-blind, placebo-controlled trial to compare rituximab, ifosfamide, carboplatin and etoposide (R-ICE) + dacetuzumab with R-ICE + placebo in patients with DLBCL who relapsed after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) (ClinicalTrials.gov #NCT00529503). The primary endpoint was complete response (CR); additional endpoints included failure-free survival and overall survival (OS). Overall, 151 patients were randomized (75 dacetuzumab, 76 placebo). No notable differences between arms in demographics or subsequent treatment parameters were observed. Cytopenias, cough and infection were more frequent with dacetuzumab. Futility analysis failed to demonstrate higher CR rates with dacetuzumab (36% dacetuzumab, 42% placebo); consequently, enrollment was stopped. Unplanned post hoc analysis showed that patients who underwent subsequent autologous stem cell transplant experienced improvement in OS (hazard ratio = 0.195, p = 0.004), which may be explained by potential immunomodulatory effects of dacetuzumab on antigen-presenting cells.

• MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• ifosfamid aplikace a dávkování   škodlivé účinky   MeSH
• indukce remise MeSH
• Kaplanův-Meierův odhad MeSH
• karboplatina aplikace a dávkování   škodlivé účinky   MeSH
• kašel chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• prednisolon aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři MeSH
• trombocytopenie chemicky indukované   MeSH
• vinkristin aplikace a dávkování   MeSH
• výsledek terapie MeSH
• záchranná terapie metody   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 II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH