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
- antitumorózní látky * terapeutické užití 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
- 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
GOYA was a randomized phase 3 study comparing obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) vs standard-of-care rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). This retrospective analysis of GOYA aimed to assess the association between progression-free survival (PFS) and overall survival (OS) with positron emission tomography (PET)-based complete response (CR) status. Overall, 1418 patients were randomly assigned to receive 8 21-day cycles of obinutuzumab (n = 706) or rituximab (n = 712) plus 6 or 8 cycles of CHOP. Patients received a mandatory fluoro-2-deoxy-d-glucose-PET/computed tomography scan at baseline and end of treatment. After a median follow-up of 29 months, the numbers of independent review committee-assessed PFS and OS events in the entire cohort were 416 (29.3%) and 252 (17.8%), respectively. End-of-treatment PET CR was highly prognostic for PFS and OS according to Lugano 2014 criteria (PFS: hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.19-0.38; P < .0001; OS: HR, 0.12; 95% CI, 0.08-0.17; P < .0001), irrespective of international prognostic index score and cell of origin. In conclusion, the results from this prospectively acquired large cohort corroborated previously published data from smaller sample sizes showing that end-of-treatment PET CR is an independent predictor of PFS and OS and a promising prognostic marker in DLBCL. Long-term survival analysis confirmed the robustness of these data over time. Additional meta-analyses including other prospective studies are necessary to support the substitution of PET CR for PFS as an effective and practical surrogate end point. This trial was registered at www.clinicaltrials.gov as #NCT01287741.
- MeSH
- difúzní velkobuněčný B-lymfom * diagnostické zobrazování farmakoterapie MeSH
- doba přežití bez progrese choroby MeSH
- lidé MeSH
- PET/CT * MeSH
- pozitronová emisní tomografie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
