RESUMO
We explored patient front-line treatment preferences in newly diagnosed stage III/IV classic Hodgkin lymphoma (cHL). The CONNECT patient survey, administered online from 30 December 2020 to 1 March 2021, examined preferences overall and by age at diagnosis in 182 adult patients diagnosed with stage III/IV cHL within the past 10 years in the United States. At diagnosis, patients' median age was 36 years; 66% of patients were younger (aged 16-41 years) and 34% older (aged 42-85 years). When asked about initial treatment goals, 74% of patients ranked cure as their first or second goal (86% younger vs. 52% older patients; p < 0.001). At diagnosis, 72% of patients preferred aggressive treatment, and 85% were willing to accept more short-term risks in exchange for a better-working therapy long term. For long-term risks, younger versus older patients were significantly more concerned about second cancers (p < 0.001) and fertility issues (p = 0.007), whereas older patients were more concerned about lung damage (p = 0.028) and infections (p < 0.001). Most patients (94%) reported having a caregiver at some point, but 99% of these patients retained some control of treatment decisions. Collectively, these survey results highlight patient treatment preferences and differences in treatment goals and long-term side effect concerns based on patient age.
Assuntos
Doença de Hodgkin , Adulto , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Estudos Transversais , Preferência do Paciente , Inquéritos e QuestionáriosRESUMO
This systematic literature review evaluated frontline treatment burden in pediatric and adolescent/young adult (AYA) patients with high-risk classical Hodgkin lymphoma (cHL) among studies originating from the United States. Data were extracted from 32 publications (screened: total, n = 3115; full-text, n = 98) representing 12 studies (randomized controlled trials [RCTs], n = 2; non-comparative, non-randomized, n = 7; observational, n = 3). High-risk disease definitions varied across studies. Five-year event-free survival (EFS)/progression-free survival (PFS) was 86%-100% and 79%-94%, and complete response rates were 35%-100% and 5%-64% for brentuximab vedotin (BV)-containing and chemotherapy-alone regimens, respectively. In identified RCTs, BV-containing compared with chemotherapy-alone regimens demonstrated significantly longer 3-year EFS/5-year PFS. Hematological and peripheral neuropathy were the most commonly reported adverse events of interest, although safety data were inconsistently reported. Few studies evaluated humanistic and no studies evaluated economic burden. Results from studies with the highest quality of evidence indicate an EFS/PFS benefit for frontline BV-containing versus chemotherapy-alone regimens for pediatric/AYA patients with high-risk cHL.
Assuntos
Doença de Hodgkin , Adolescente , Criança , Humanos , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Prognóstico , Taxa de SobrevidaRESUMO
Aim: To understand US physicians' frontline (1L) treatment preferences/decision-making for stage III/IV classic Hodgkin lymphoma (cHL). Materials & methods: Medical oncologists and/or hematologists (≥2 years' practice experience) who treat adults with stage III/IV cHL were surveyed online (October-November 2020). Results: Participants (n = 301) most commonly considered trial efficacy/safety data and national guidelines when selecting 1L cHL treatments. Most physicians (91%) rated overall survival (OS) as the most essential attribute when selecting 1L treatment. Variability was seen among regimen selection for hypothetical newly diagnosed patients, with OS cited as the most common reason for regimen selection. Conclusion: While treatment selection varied based on patient characteristics, US physicians consistently cited OS as the top factor considered when selecting a 1L treatment for cHL.
Classic Hodgkin lymphoma (cHL) is a type of cancer that grows in lymph nodes. The researchers created a survey to assess how doctors in the USA choose medicine to treat patients who are newly diagnosed with an advanced stage of cHL (stage 3 or 4 out of 4 stages). We surveyed 301 doctors who treat patients with cHL. When choosing a medicine to treat cHL, most doctors said they consider results from research studies, how well the medicine works, information on the medicine's safety and recommendations in official guidelines. Most doctors said that overall survival (how long the patient survives after being diagnosed with cHL) is the most important outcome they consider when choosing a medicine to treat cHL. During the survey, doctors saw four unique patient profiles. These profiles differed in age, disease stage (how far along the cHL is) and other illnesses the patient has. While medicine choice was different across profiles, overall survival was still the reason for choosing each individual patient's medicine. These survey results show that doctors in the USA highly consider overall survival when choosing medicine for patients newly diagnosed with an advanced stage of cHL.
Assuntos
Tomada de Decisão Clínica , Doença de Hodgkin , Médicos , Adulto , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Estadiamento de Neoplasias , Análise de SobrevidaRESUMO
BACKGROUND: Since Food and Drug Administration approval of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (Aâ +â CHP) as initial therapy for previously untreated CD30-expressing peripheral T-cell lymphoma (PTCL), there has been limited research on real-world patient characteristics, treatment patterns, and clinical outcomes. METHODS: We retrospectively analyzed claims of patients with PTCL treated with frontline Aâ +â CHP or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) using the Symphony Health Solutions database. Adults with International Classification of Diseases-9/10 PTCL diagnosis codes who initiated Aâ +â CHP or CHOP between November 2018 and July 2021 were included. A 1:1 propensity score matching analysis was performed that adjusted for potential confounders between groups. RESULTS: A total of 1344 patients were included (Aâ +â CHP, nâ =â 749; CHOP, nâ =â 595). Before matching, 61% were men; median age at index was 62 (Aâ +â CHP) and 69 (CHOP) years. The most common Aâ +â CHP-treated PTCL subtypes were systemic anaplastic large cell lymphoma (sALCL; 51%), PTCL-not otherwise specified (NOS; 30%), and angioimmunoblastic T-cell lymphoma (AITL; 12%); the most common CHOP-treated subtypes were PTCL-NOS (51%) and AITL (19%). After matching, similar proportions of patients treated with Aâ +â CHP and CHOP received granulocyte colony-stimulating factor (89% vs. 86%, Pâ =â .3). Fewer patients treated with Aâ +â CHP received subsequent therapy than CHOP overall (20% vs. 30%, Pâ <â .001) and specifically with the sALCL subtype (15% vs. 28%, Pâ =â .025). CONCLUSIONS: Characteristics and management of this real-world PTCL population who were older and had a higher comorbidity burden than that in the ECHELON-2 trial demonstrate the importance of retrospective studies when assessing the impact of new regimens on clinical practice.
Assuntos
Linfoma de Células T Periférico , Adulto , Masculino , Humanos , Feminino , Brentuximab Vedotin/uso terapêutico , Estudos Retrospectivos , Prednisona , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/patologia , Pontuação de Propensão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , DoxorrubicinaRESUMO
PURPOSE: As part of the CONNECT study, we evaluated the caregiver role in treatment decision-making when caring for patients with classic Hodgkin lymphoma (cHL) in the USA. METHODS: The CONNECT caregiver survey was administered online December 2020-March 2021 to self-identified adult caregivers of cHL patients recruited from patient referrals and online panels. The caregiver's role in treatment decision-making, health-related quality of life (HRQoL, PROMIS-Global), and work impacts (WPAI:CG) were assessed. RESULTS: We surveyed 209 caregivers (58% women; median age 47 years; 54% employed; 53% spouse/partner); 69% of patients cared for were diagnosed with cHL in the past 1-2 years, with 48% having stage III/IV cHL and 29% in remission. More spouse/partner than other caregivers were involved in caregiving at symptom onset (61% vs 27%), whereas more other than spouse/partner caregivers began after first treatment (34% vs 5%). Cure, caregivers' top treatment goal (49%), was rated higher by spouse/partner than other caregivers (56% vs 42%). More spouse/partner than other caregivers were involved in treatment option discussions with physicians (52% vs 28%), were involved in patients' treatment decisions (54% vs 23%), and were aligned with patients' treatment goals (93% vs 79%). While caregivers reported HRQoL similar to that of the general population, nearly 30% of employed caregivers reported work impairment. CONCLUSION: Cure was caregivers' top treatment goal. Spouse/partner vs other caregivers were more involved, were involved earlier, and reported greater alignment with patient treatment goals and decision-making. Caregivers reported good HRQoL; however, caregiving impacted work productivity regardless of patient relationship.
Assuntos
Cuidadores , Doença de Hodgkin , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Qualidade de Vida , Estudos Transversais , Doença de Hodgkin/terapia , Inquéritos e QuestionáriosRESUMO
Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.
Assuntos
Antineoplásicos/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoconjugados/administração & dosagem , Fatores Imunológicos/administração & dosagem , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Brentuximab Vedotin , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Método Duplo-Cego , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imunoconjugados/efeitos adversos , Fatores Imunológicos/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Vincristina/administração & dosagemRESUMO
The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined with a 1-dimensional measurement, can change a patient's risk grouping and thus the treatment approach. We hypothesized that 3-dimensional measurements of disease burden obtained from baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of patients with stage I-II HL treated at our institution between 2003 and 2013. Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual contouring and (2) subthresholding of these contours to give the tumor volume with standardized uptake value ≥2.5. MTV and TLG were extracted from the threshold volumes (MTVt, TLGt) and from the manually contoured soft-tissue volumes. At a median follow-up of 4.96 years for the 267 patients evaluated, 27 patients were diagnosed with relapsed or refractory disease and 12 died. Both MTVt and TLGt were highly correlated with freedom from progression and were dichotomized with 80th percentile cutoff values of 268 and 1703, respectively. Consideration of MTV and TLG enabled restratification of early unfavorable HL patients as having low- and high-risk disease. We conclude that MTV and TLG provide a potential measure of tumor burden to aid in risk stratification of early unfavorable HL patients.
Assuntos
Doença de Hodgkin/classificação , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Fluordesoxiglucose F18/metabolismo , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30+ peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.8+ to 66.0+ months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV+CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Expressão Gênica , Antígeno Ki-1/genética , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imunoconjugados/administração & dosagem , Estimativa de Kaplan-Meier , Antígeno Ki-1/metabolismo , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto JovemRESUMO
Lack of consensus for first-line marginal zone lymphoma (MZL) treatment and toxicities associated with currently available systemic therapies have inspired evaluation of immunotherapeutic agents yielding robust outcomes with improved tolerability. We previously reported durable efficacy with first-line lenalidomide and rituximab (R2 ) in follicular lymphoma, MZL and small lymphocytic lymphoma with a subsequent long-term follow-up shown here in MZL patients. This phase 2 investigator-initiated study included previously untreated, stage III/IV MZL patients treated with lenalidomide 20 mg/day on days 1-21 and rituximab 375 mg/m2 on day 1 of each 28-day cycle, continuing in responders for ≥6-12 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints were complete and partial response (CR, PR), safety, and progression-free survival (PFS). The ORR was 93% with 70% attaining CR/CR unconfirmed. At median follow-up of 75·1 months, median PFS was 59·8 months and 5-year OS was 96%. Most non-haematological adverse events (AE) were grade 1/2. Grade 3 haematological AEs were neutropenia (33%) and leucopenia (7%), and grade 4 were leucopenia (3%) and thrombocytopenia (3%). Two patients died of secondary malignancies; no treatment-related fatalities occurred. With extended follow-up, outcomes for MZL patients receiving R2 were robust with no unexpected late or delayed toxicities.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Lenalidomida/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Inibidores da Angiogênese/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Feminino , Seguimentos , Humanos , Lenalidomida/farmacologia , Masculino , Pessoa de Meia-Idade , Rituximab/farmacologiaRESUMO
In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well-tolerated in previously untreated patients with advanced-stage, indolent non-Hodgkin lymphoma (iNHL). After a median patient follow-up of more than 108 months, we performed an intent-to-treat analysis of our 83 participants. Progression-free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten-year PFS rates for those with beta-2-microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10-year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long-term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10-year follow-up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Doenças da Medula Óssea/mortalidade , Ciclofosfamida/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Pentostatina/administração & dosagem , Rituximab/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The genomic landscape of Hodgkin lymphoma (HL) has been difficult to characterize due to the paucity of neoplastic cells and an abundant microenvironment. Such characterization is needed in order to improve treatment strategies. MATERIALS AND METHODS: We performed comprehensive genomic profiling (CGP) using targeted next-generation sequencing on archival formalin-fixed paraffin embedded tumor samples from 63 patients to analyze the landscape of HL. RESULTS: CGP was successful for 49/63 archival specimens (78%), and revealed aberrations impacting genes including B2M, TP53, and XPO1 (E571). Of the 34 patients for whom total mutation burden (TMB; mutations/megabase [Mb]) was assessed, 5 (15%) had high TMB (≥20 mutations/Mb), 18 (53%) had intermediate TMB (6-19 mutations/Mb), and 11 (32%) had low TMB (≤5 mutations/Mb). We next tested 13 patients' plasma cell-free DNA with droplet digital polymerase chain reaction for the presence of XPO1 E571 mutation, which was confirmed in the plasma of 31% of patients. In three patients with serially collected plasma samples, XPO1 E571K allelic frequency changes corresponded with changes in tumor size on conventional radiographic imaging. CONCLUSION: The study demonstrates that comprehensive genomic profiling of archival Hodgkin lymphoma tumor samples is feasible and leads to the identification of genes that are recurrently mutated and that Hodgkin lymphoma has increased mutation burden in the majority of samples analyzed. Furthermore, tracking of XPO1 E571 mutant allele frequency in a subset of patients may also represent a potential disease-monitoring strategy and warrants further investigation. IMPLICATIONS FOR PRACTICE: This study provides the first evidence that comprehensive genomic profiling can be performed to map the genomic landscape of Hodgkin lymphoma and that a subpopulation of patients has mutations in TP53, B2M, XPO1, and other genes. It was found that 15% of patients have high mutation burden, which, in cancers such as melanoma, may indicate sensitivity to immune checkpoint inhibitors, and may thus be explored for Hodgkin lymphoma. Lastly, this work demonstrates that changes in the mutant allele frequency of XPO1 in serially collected plasma cell-free DNA samples correspond with treatment outcomes measured with conventional radiographic imaging.
Assuntos
Perfilação da Expressão Gênica/métodos , Genômica/métodos , Doença de Hodgkin/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Adulto JovemRESUMO
This pivotal phase 2 study evaluated the safety and efficacy of brentuximab vedotin in patients with relapsed or refractory (R/R) systemic anaplastic large cell lymphoma (ALCL). After a median observation period of approximately 6 years from first treatment, we examined the durability of remission, progression-free survival (PFS), overall survival (OS), and safety outcomes of patients treated on this trial. Among all enrolled patients (n = 58), no progressions were observed beyond 40 months, and median OS was not reached. Patients with a complete response (CR), as assessed by the investigator (38 of 58, 66%), continued to demonstrate improved outcomes with neither median OS nor PFS reached. Of the 38 CR patients, 16 received a consolidative stem cell transplant (SCT) with median PFS not reached. Among patients who were on-study and in remission at study closure, 16 patients had not received any new treatment after single-agent brentuximab vedotin other than consolidative SCT. Among this subset of 16 patients, 8 received SCT, and the remaining 8 patients (14% of all enrolled patients) remained in sustained remission without consolidative SCT or any new anticancer therapy. Thirty-three patients experienced peripheral neuropathy, among whom, the majority (30 of 33, 91%) had experienced resolution or improvement at their last assessment. These final results, which demonstrated a high rate of peripheral neuropathy resolution, and durable remissions in a subset of patients with relapsed or refractory systemic ALCL, provide evidence that single-agent brentuximab vedotin may be a potentially curative treatment option. This trial was registered at www.clinicaltrials.gov as #NCT00866047.
Assuntos
Imunoconjugados/uso terapêutico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Adolescente , Adulto , Idoso , Brentuximab Vedotin , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imunoconjugados/efeitos adversos , Estudos Longitudinais , Linfoma Anaplásico de Células Grandes/complicações , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/etiologia , Indução de Remissão , Terapia de Salvação/métodos , Transplante de Células-Tronco , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P = .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P = .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate that is highly effective in patients with relapsed/refractory anaplastic large cell lymphoma (ALCL). However, survival outcomes following suboptimal response or subsequent relapse are not well known. We conducted a multicenter study analyzing outcomes of patients with relapsed/refractory ALCL who have received BV with a secondary focus on survival after progression following BV. A total of 56 patients were treated with BV for relapsed or refractory ALCL. The overall response rate to BV was 73% with complete response (CR) rate of 46%. The median failure-free survival and overall survival (OS) after BV were 15.5 month and not reached, respectively. The median duration of response was 27.6 months in patients who achieved CR by BV, while the median OS of those who did not achieve CR by BV was 9.5 months. There was no significant difference in OS between those who underwent stem cell transplant (SCT) and those who did not in patients who achieved CR after BV. However, if patients were in PR after BV, SCT was associated with significantly longer OS. Thirty patients experienced progressive disease on BV or required a subsequent treatment. The median OS after BV failure was 2.9 months with 2-year OS of 27.1%. There were seven long-term survivors (≥12 months) following failure. After an adequate response to subsequent salvage therapy, five patients underwent subsequent SCT (three allogeneic and two autologous), four of which were long-term survivors (17+, 25+, 32+, and 50+ months). In conclusion, BV failure is associated with a poor outcome in patients with ALCL, which defines a small but important group with unmet need. SCT may have benefit in patients with relapsed/refractory ALCL who failed BV.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Imunoconjugados/uso terapêutico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Brentuximab Vedotin , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Linfoma Anaplásico de Células Grandes/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Retratamento , Análise de Sobrevida , Falha de Tratamento , Resultado do Tratamento , Adulto JovemRESUMO
Stage I non-Hodgkin lymphoma (NHL) is rare; prognostic impact of different histologic subtypes and treatment modality is still unclear. We used the Surveillance, Epidemiology and End Results (SEER) database to evaluate survival outcomes among adult patients (age ≥ 18 years, N = 58,230) diagnosed with stage I NHL of various histologic subtypes between 1998 and 2014. Five-year disease-specific survival of patients with stage I diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL), and peripheral T cell lymphoma (PTCL) was 82%, 92%, 95%, 89%, 78%, 77%, and 77%, respectively. The median disease-specific survival was not reached in all histologic subtypes analyzed; however, there does not appear to be a plateau in disease-specific survival of patients with stage I NHL irrespective of subtypes. Although lymphoma was the most common cause of death (40.7%), death from other cancer (17.4%) and cardiovascular disease (13.6%) were also frequent. Chemotherapy appeared favorably associated with OS in patients with DLBCL, BL, and MCL while patients with FL, MZL, SLL, and PTCL who require chemotherapy for initial treatment showed shorter OS. Patients with stage I NHL have favorable disease-specific survival; however, no plateau was seen regardless of histologic subtypes thus suggesting that patients may need attention and follow-up even in aggressive lymphomas after 5 years of remission.
Assuntos
Bases de Dados Factuais , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
PURPOSE: The authors examined the prevalence of a histologic change of ocular adnexal lymphoma (OAL) grade in patients with a history of lymphoma in nonocular sites. METHODS: In this retrospective study, the authors reviewed the clinical and pathological data of 209 patients with OAL treated by the senior author during 2000 to 2017. RESULTS: Of 209 patients with OAL, 65 (31%) had a history of lymphoma. In 54 of the 65 patients (83%), the original lymphoma and OAL were of the same histologic type. In 8 of the 65 patients (12.3%), the OAL was more indolent than the original lymphoma: 6 patients with a history of diffuse large B-cell lymphoma, one of mantle cell lymphoma, and one of grade 3 follicular lymphoma had biopsy-proven extranodal marginal-zone lymphoma in the orbital area. Two additional patients (3%) with a history of chronic lymphocytic leukemia developed OAL: diffuse large B-cell lymphoma in one patient and extranodal marginal-zone lymphoma in the other. One patient (1.5%) with a history of a low-grade follicular lymphoma relapsed as a different low-grade histology of extranodal marginal-zone lymphoma. Lower-grade OAL than the original lymphoma was more common than higher-grade OAL than the original lymphoma (p = 0.048). CONCLUSIONS: In this cohort of 209 patients with OAL, the authors found that nearly one third had a history of lymphoma, 17% of whom had a different histologic type of lymphoma in the orbit, more commonly a more indolent type. This underscores the importance of biopsy of OAL even in patients with a known history of lymphoma to determine the histologic subtype of orbital lymphoma and to help guide appropriate treatment.
Assuntos
Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma/epidemiologia , Estadiamento de Neoplasias , Neoplasias Orbitárias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Seguimentos , Humanos , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Neoplasias Orbitárias/diagnóstico , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
We conducted a prospective phase 2 trial of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) with autologous stem cell transplantation (ASCT) in patients with primary refractory or poor-risk relapsed Hodgkin lymphoma (HL) (ie, extranodal relapse or within 1 year of frontline therapy). The trial was powered to detect an improvement in 2-year progression-free survival (PFS) from a historical 50% using a BEAM regimen (carmustine/etoposide/cytarabine/melphalan) to 65%. We compared the study population with all other concurrent patients who were eligible for the trial but instead received the BEAM regimen at our center. No patient received post-ASCT maintenance therapy. The Gem/Bu/Mel trial enrolled 80 patients with a median age of 31 years, 41% with primary refractory HL and 59% with relapsed HL (36% extranodal relapses), and 30% with positron emission tomography (PET)-positive lesions at ASCT. The concurrent BEAM (n = 45) and Gem/Bu/Mel cohorts were well balanced except for higher rates of bulky relapse and PET-positive tumors in the Gem/Bu/Mel cohort. There were no transplantation-related deaths in either cohort. At a median follow-up of 34.5 months (range, 26 to 72 months), Gem/Bu/Mel was associated with better 2-year PFS (65% versus 51%; P = .008) and overall survival (89% versus 73%; P = .0003). In conclusion, our data show that Gem/Bu/Mel is safe, in this nonrandomized comparison yielding improved outcomes compared with a concurrently treated and prognostically matched cohort of patients with primary refractory or poor-risk relapsed HL receiving BEAM.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Terapia de Salvação/métodos , Adulto , Bussulfano/uso terapêutico , Carmustina/uso terapêutico , Citarabina/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Etoposídeo/uso terapêutico , Doença de Hodgkin/mortalidade , Humanos , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Terapia de Salvação/mortalidade , Análise de Sobrevida , Transplante Autólogo , Adulto Jovem , GencitabinaRESUMO
BACKGROUND: Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or synergistic effects in preclinical trials with known effective agents. METHODS: This is a report of a prospective phase 2 trial of bortezomib added to rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (BzR-hyperCVAD)/rituximab, high-dose methotrexate, and high-dose cytarabine (BzR-MA) for 95 patients with newly diagnosed MCL. RESULTS: The overall and complete response rates were 100% and 82%, respectively. Hematologic toxicity was high but expected and did not lead to an increased incidence of neutropenic fever or dose reductions in comparison with a similar reported regimen without bortezomib. After a median follow-up of 44 months, the median overall survival had not been reached, and the time to treatment failure (TTF) was 55 months, which is not different from that of historical controls. CONCLUSIONS: BzR-hyperCVAD/BzR-MA at the dose and schedule studied produced high rates of response and a TTF similar to that of historical reports without bortezomib. Cancer 2018;124:2561-9. © 2018 American Cancer Society.