RESUMEN
Retrospective studies have suggested that older adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have better survival rates when treated using a pediatric ALL regimen administered by pediatric treatment teams. To address the feasibility and efficacy of using a pediatric treatment regimen for AYA patients with newly diagnosed ALL administered by adult treatment teams, we performed a prospective study, CALGB 10403, with doses and schedule identical to those in the Children's Oncology Group study AALL0232. From 2007 to 2012, 318 patients were enrolled; 295 were eligible and evaluable for response. Median age was 24 years (range, 17-39 years). Use of the pediatric regimen was safe; overall treatment-related mortality was 3%, and there were only 2 postremission deaths. Median event-free survival (EFS) was 78.1 months (95% confidence interval [CI], 41.8 to not reached), more than double the historical control of 30 months (95% CI, 22-38 months); 3-year EFS was 59% (95% CI, 54%-65%). Median overall survival (OS) was not reached. Estimated 3-year OS was 73% (95% CI, 68%-78%). Pretreatment risk factors associated with worse treatment outcomes included obesity and presence of the Philadelphia-like gene expression signature. Use of a pediatric regimen for AYAs with ALL up to age 40 years was feasible and effective, resulting in improved survival rates compared with historical controls. CALGB 10403 can be considered a new treatment standard upon which to build for improving survival for AYAs with ALL. This trial was registered at www.clinicaltrials.gov as #NCT00558519.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Adulto , Esquema de Medicación , Femenino , Estudio Históricamente Controlado , Humanos , Masculino , Obesidad , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudios Prospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Acute promyelocytic leukemia (APL) is a unique leukemia subtype requiring specialized treatment including all-trans retinoic acid (ATRA). A prior report demonstrated worse outcome among young children <5 years old compared with older children. METHODS: We evaluated outcomes for pediatric patients (<18 years old; N = 83) with APL treated on North American intergroup study CALGB 9710 at Children's Oncology Group sites. Induction and consolidation included ATRA, cytarabine, and anthracyclines. Patients ≥15 years old were randomized to addition of arsenic trioxide (ATO) consolidation. All patients were randomized to ATRA maintenance with versus without oral chemotherapy. RESULTS: The estimated 5-year overall survival (OS) rate was 82%, and the event-free survival (EFS) rate was 54%. Seven patients (8.4%) died during induction due to coagulopathy. Maintenance randomization demonstrated that addition of oral chemotherapy to ATRA significantly reduced relapse rate, but difference in EFS did not reach statistical significance (P = 0.12; 5-year rates [95% CI]: 41% [17%-64%] ATRA only vs 72% [56%-88%] ATRA plus chemotherapy). There was no difference (P = 0.93) in EFS for age <5 years versus 5-12.99 years versus 13-17.99 years (5-year rates: 56%, 47%, and 45%, respectively). Among adolescents 15-17.99 years old in the ATO randomization, there was a significantly lower relapse risk at 5 years for those receiving ATO (0% ATO vs 44% no ATO; P = 0.02). CONCLUSION: Our data demonstrate that intensified ATRA, cytarabine, and anthracycline chemotherapy is effective for pediatric APL including very young patients, but early deaths and relapses remain barriers to cure. Further improvements are likely with incorporation of ATO into pediatric APL regimens.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Adolescente , Niño , Preescolar , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Leucemia Promielocítica Aguda/patología , Masculino , Pronóstico , Tasa de Supervivencia , Tretinoina/administración & dosificaciónRESUMEN
Light-chain (AL) amyloidosis remains incurable despite recent therapeutic advances. Given the activity of the lenalidomide-alkylating agent combination in myeloma, we designed this phase 2 trial of lenalidomide, cyclophosphamide, and dexamethasone in AL amyloidosis. Thirty-five patients, including 24 previously untreated, were enrolled. Nearly one-half of the patients had cardiac stage III disease and 28% had ≥ 3 organs involved. The overall hematologic response (≥ partial response [PR]) rate was 60%, including 40% with very-good partial response or better. Using serum-free light chain for assessing response, 77% of patients had a hematologic response. Organ responses were seen in 29% of patients and were limited to those with a hematologic response. The median hematologic progression-free survival was 28.3 months, and the median overall survival was 37.8 months. Hematologic toxicity was the predominant adverse event, followed by fatigue, edema, and gastrointestinal symptoms. A grade 3 or higher toxicity occurred in 26 patients (74%) including ≥ grade 3 hematologic toxicity in 16 patients (46%) and ≥ grade 3 nonhematologic toxicity in 25 patients (71%). Seven patients (20%) died on study, primarily because of advanced disease. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) is an effective combination for treatment of AL amyloidosis and leads to durable hematologic responses as well as organ responses with manageable toxicity. The trial was registered at www.clinicaltrials.gov (NCT00564889).
Asunto(s)
Amiloidosis/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Enfermedades Renales/tratamiento farmacológico , Talidomida/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/efectos adversos , Dexametasona/efectos adversos , Femenino , Estudios de Seguimiento , Cardiopatías/tratamiento farmacológico , Cardiopatías/metabolismo , Humanos , Cadenas Ligeras de Inmunoglobulina/metabolismo , Enfermedades Renales/metabolismo , Lenalidomida , Masculino , Persona de Mediana Edad , Talidomida/administración & dosificación , Talidomida/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Novel agents are considered standard components of induction therapy for newly diagnosed patients with multiple myeloma. We retrospectively compared the results of three consecutive phase 2 clinical trials; RD (lenalidomide/dexamethasone, n=34), CRD (cyclophosphamide/lenalidomide/dexamethasone, n=53) and CyBorD (cyclophosphamide/bortezomib/dexamethasone, n=63) (N=150). Response rates after four cycles of treatment were: ≥near complete response (nCR), 12% vs. 2% vs. 41%, P<0·0001 and very good partial response or better, 35% vs. 30% vs. 65%, P=0·0003, respectively. With all cycles of therapy considered, ≥nCR was 35%, 15% and 41%, P=0·006. However, there is no evidence that one regimen produced superior progression-free survival (PFS) (median: 3·2 vs. 2·3 vs. 2·7years, P=0·11) or overall survival (3-year: 88% vs. 79% vs. 88%, P=0·23). Transplantation did not impact PFS (median: 2·7 vs. 2·3 years, P=0·41) but was associated with improved OS (3-year: 93% vs. 75%, P≤0·001). High genetic risk patients (n=40) had earlier relapse despite lenalidomide or bortezomib (median: 2·1 vs. 2·7years, P=0·45). Grade 3/4 toxicities were least with CyBorD while CRD had most toxicity. In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80% of patients treated with modern therapeutic approaches are alive at 4years.