RESUMO
Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On the KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard-of-care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day-90 follow-up. Data were censored at day 100. Grade ≥ 3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥ 3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 and 100 were 50% bacterial and 42% viral; only 13% were grade ≥ 3. On univariate analysis, high pre-CAR-T marrow myeloma burden (≥ 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥ 3 anemia at pre-LD were associated with grade ≥ 3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection.
Assuntos
Anemia , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Trombocitopenia , Humanos , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Padrão de Cuidado , Fator Estimulador de Colônias de GranulócitosRESUMO
Despite improvements in prevention and treatment of acute graft-versus-host disease (GVHD), chronic GVHD (cGVHD) remains a significant contributor to morbidity and mortality of allogeneic transplant patients. Chronic GVHD remains a leading cause of late complications posttransplant and is impacted by donor-, patient-, and transplant-related (hematopoietic cell transplant [HCT]) factors. Advances in the biological understanding of cGVHD have provided opportunities to improve clinical interventions for prevention and treatment. Expansion of posttransplantation cyclophosphamide beyond haploidentical HCTs has transformed alternative donor, matched, and mismatch GVHD outcomes and is currently being investigated in two upcoming clinical trials network prophylaxis studies. Although corticosteroids remain the cornerstone therapy, several clinical trials are prospectively investigating the utility of using novel agents in combination with corticosteroids as upfront therapy to mitigate prolonged steroid exposure. Several treatment options for patients with steroid-refractory cGVHD are currently being investigated, and advances have resulted in ibrutinib becoming the first cGVHD agent approved by the U.S. Food and Drug Administration. We review recent advances in understanding of cGVHD pathophysiology and new approaches for the prevention and treatment of cGVHD.
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adenina/administração & dosagem , Adenina/análogos & derivados , Corticosteroides/administração & dosagem , Doença Crônica , Ciclofosfamida/administração & dosagem , Doença Enxerto-Hospedeiro/fisiopatologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Piperidinas/administração & dosagemAssuntos
Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Antígenos CD34 , Benzilaminas , Índice de Massa Corporal , Ciclamos , Fator Estimulador de Colônias de Granulócitos , Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , HumanosRESUMO
The Neotropical butterfly Dryas iulia has been collected from several locations in Thailand and Malaysia since 2007, and has been observed breeding in the wild, using introduced Passiflora foetida as a larval host plant. The butterfly is bred by a butterfly house in Phuket, Thailand, for release at weddings and Buddhist ceremonies, and we hypothesized that this butterfly house was the source of wild, Thai individuals. We compared wing patterns and COI barcodes from two, wild Thai populations with individuals obtained from this butterfly house. All Thai individuals resemble the subspecies D. iulia modesta, and barcodes from wild and captive Thai specimens were identical. This unique, Thai barcode was not found in any of the 30 specimens sampled from the wild in the species' native range, but is most similar to specimens from Costa Rica, where many exporting butterfly farms are located. These data implicate the butterfly house as the source of Thailand's wild D. iulia populations, which are currently so widespread that eradication efforts are unlikely to be successful.