Asunto(s)
Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Linfocitos B/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Linfoma de Células B/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/biosíntesis , Anticuerpos Antivirales/sangre , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Linfocitos B/efectos de los fármacos , Instituciones Oncológicas , Estudios de Cohortes , Femenino , Personal de Salud , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/biosíntesis , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Inmunoterapia Adoptiva/efectos adversos , Institucionalización , Linfoma de Células B/terapia , Linfoma de Células T/inmunología , Linfoma de Células T/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Casas de Salud , Pacientes , Estudios ProspectivosRESUMEN
The CORAL study highlighted the need to develop novel salvage regimens in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) previously treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Carfilzomib (CFZ) can overcome rituximab chemotherapy resistance in lymphoma preclinical models by targeting the ubiquitin-proteasome system. We conducted an investigator initiated, single-center, open-label, prospective phase 1 study evaluating the safety and efficacy of CFZ in combination with rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) in high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) eligible patients with R/R DLBCL (NCT01959698). In the dose-escalation phase, 18 patients were enrolled at 6 dose levels with no dose-limiting toxicities noted. CFZ 45 mg/m2 was selected as the recommended dose for expansion. Eleven additional patients were enrolled in the dose-expansion phase. Overall response rate (ORR) was 66% (48% CR; 17% PR); 52% patients underwent HDC-ASCT. An ORR of 85% was observed in patients with nongerminal center B-cell-like (non-GCB) DLBCL compared with only 13% in those with GCB DLBCL. Median progression-free survival (PFS) was 15.2 months (5.1 months, not reached [NR]), and median overall survival (OS) was 22.6 months (6.8 months, NR). Patients with non-GCB subtype had a significantly longer PFS (NR vs 6.6 months; P = .0001) and OS (NR vs 6.6 months; P = .001) than those with GCB subtype. C-R-ICE is well tolerated in patients with R/R DLBCL with toxicities comparable to rituximab, ifosfamide, carboplatin, and etoposide therapy. Our data show that patients with non-GCB DLBCL benefit significantly from incorporating CFZ into second-line therapy and HDC-ASCT.