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1.
Ann Hematol ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39243312

RESUMO

INTRODUCTION: We aimed to compare outcomes of patients with AML treated with frontline hypomethylating agent and venetoclax (HMA + Ven) who achieved complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS) as defined by ELN 2022. METHODS: Patients with AML seen at Moffitt Cancer Center between 2018 and 2022 and treated with HMA + Ven were retrospectively evaluated. RESULTS: About 120 patients achieved blast clearance with best response of CR in 52 (43.3%), CRh in 22 (18.3%), CRi in 31 (25.8%) and MLFS in 15 (12.5%) patients. Greater proportion of patients with MLFS had a prior myeloid malignancy (p = 0.003) and were treated with prior HMA (p < 0.001). Patients that achieved MLFS as their best response had inferior OS compared to the CR/CRh/CRi cohort (8 months vs. 27 months; p < 0.001). RFS was also worse for the MLFS cohort. CONCLUSION: To the best of our knowledge, this is the largest study analyzing differences in outcomes of AML patients treated with HMA + Ven based on best response. We noted that prior myeloid malignancy and use of HMA led to more MLFS as best response compared to CR/CRi. The OS and RFS were inferior for MLFS cohort.

2.
Ann Hematol ; 103(6): 1941-1945, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38634915

RESUMO

Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch. A total of 390 patients were treated with dasatinib during their course of treatment for CP-CML. A total of 69 patients (17.6%) developed any grade of PE. About 33 (48%) patients developed CTCAE grade 2 PE, 34 (49%) grade 3 and only 1 patient developed grade 4 PE. Recurrence of PE was observed in 34 (49%) patients. While only 12 patients (17.3%) continued using dasatinib after development of PE, dasatinib was discontinued in the other 57 patients. Therapy was switched to bosutinib in 13 patients out of which 6 (46%) patients re-developed PE. While only 12.5% patients developed re-accumulation of pleural fluid in patients switched to imatinib, none of the patients switched to nilotinib re-developed PE. A change in TKI to bosutinib was associated with a 46% risk of recurrence of PE in patients who develop PE on dasatinib for the treatment of CP-CML. The incidence of recurrent PE was markedly lower in patient switched to imatinib or nilotinib.


Assuntos
Dasatinibe , Derrame Pleural , Inibidores de Proteínas Quinases , Humanos , Dasatinibe/efeitos adversos , Dasatinibe/administração & dosagem , Dasatinibe/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Idoso , Derrame Pleural/induzido quimicamente , Derrame Pleural/epidemiologia , Adulto , Incidência , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Idoso de 80 Anos ou mais , Quinolinas/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Substituição de Medicamentos , Compostos de Anilina/efeitos adversos , Compostos de Anilina/uso terapêutico , Compostos de Anilina/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/uso terapêutico , Adulto Jovem , Estudos Retrospectivos , Pirimidinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico
3.
Clin Lymphoma Myeloma Leuk ; 24(6): 400-406, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38429222

RESUMO

BACKGROUND: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment. PATIENTS AND METHODS: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival. We leveraged our larger sample to analyze the impact of cytogenetic/molecular features on the odds of CR/CRi. RESULTS: CR/CRi was achieved among 32 of 67 (48%) patients, and MRD negativity was recorded among 10 of 12. NPM1 and IDH 1 or 2 mutations increased the odds of CR/CRi, as did increasing time from alloHCT to relapse. Fourteen patients subsequently received donor lymphocyte infusions or a second alloHCT. Responses lasted a median of 17.8 months (95% CI, 7.2 months to not reached), and responders had a greater median overall survival of 19.7 months (95% CI, 7.6-51.5 months) compared to 2.9 months among nonresponders (95% CI, 1.8-4.4 months; log-rank P < .01). Treatment was well tolerated, but prolonged cytopenias were common and most patients required reduction in the number of venetoclax days per cycle. CONCLUSION: These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases. These responses can be durable and profound as evidenced by conversion to MRD negativity.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Nucleofosmina , Sulfonamidas , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Masculino , Feminino , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Retrospectivos , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva
4.
Haematologica ; 109(7): 2157-2164, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299605

RESUMO

The patterns of low-risk myelodysplastic syndrome (MDS) progression and the clinical and molecular features of those patterns have not been well described. We divided our low-risk (LR) MDS patients (N=1,914) into 4 cohorts: 1) patients who remained LR-MDS (LR-LR; N=1,300; 68%), 2) patients who progressed from LR to high-risk (HR) MDS (LR-HR) without transformation into acute myeloid leukemia (AML) (N=317; 16.5%), 3) patients who progressed from LR to HR MDS and then AML (LR-HR-AML; N=124; 6.5%), and 4) patients who progressed from LR MDS directly to AML (LR-AML; N=173; 9%). Risk factors for progression included: male gender, low absolute neutrophil count (ANC), low platelet count, high bone marrow (BM) blasts, ferritin >1000 mcg/L, albumin <3.5 g/dL, multi-lineage dysplasia (MLD), and lack of ring sideroblasts. Among patients with marked BM fibrosis (N=49), 18% progressed directly to AML. Somatic mutations (SM) associated with an increased risk of direct or indirect AML progression included SRSF2 and NRAS. SM in IDH1, IDH2 and NPM1 were more common in patients with direct AML transformation. SM associated with progression to higher risk disease only, without AML transformation, were ASXL1, TP53, RUNX1, and CBL. SF3B1 mutation was associated with less progression. About 171 patients (13.1% of all LR-LR patients) died within two years of diagnosis of LR-MDS without disease progression. Among the 61 cases with documented cause of death, 18 patients (29.5%) died from cytopenia and MDS-related complications. Identifying patterns of disease progression of LR MDS patients and their predictive factors will be crucial to be able to tailor therapy accordingly.


Assuntos
Progressão da Doença , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Nucleofosmina , Humanos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Masculino , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Fatores de Risco , Mutação , Prognóstico , Adulto Jovem , Adolescente
6.
Clin Lymphoma Myeloma Leuk ; 23(10): e315-e322, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37558530

RESUMO

BACKGROUND: The phase III trial that led to the approval of CPX-351 for treating secondary acute myeloid leukemia (sAML) in 2017 did not study the effect of specific mutations on outcomes. METHODS: This retrospective study was done to evaluate the effect of next-generation sequencing (NGS) results at the time of best response and before allogeneic stem cell transplant (alloSCT) in patients treated with CPX-351 as frontline therapy for sAML between 2017 and 2021. RESULTS: The most common mutations seen were DNMT3A (n = 17, 29.8%), SRSF2 (n = 13, 22.8%), RUNX1 (n = 13, 22.8%), TET2 (n = 9, 15.8%), ASXL1 (n = 9, 15.8%), and BCOR (n = 9, 15.8%). Median OS (mOS) for the entire cohort was 47 months. Though 64.7% patients cleared the DNMT3A mutation, only 44.4% and 22.2% of patients cleared the TET2 and ASXL1 mutations, respectively. The mOS for patients who cleared their mutations vs. for those who did not was not significantly longer (46 vs. 30 months; P = .991). The relapse-free survival (RFS) for patients who cleared mutations was numerically longer compared to those who had persistent mutations; however, this did not reach statistical significance (44 months vs. 26 months; P = .786). CONCLUSION: This is the first study reporting NGS at best response and before alloSCT and its effect on OS and RFS. We found that OS and RFS were numerically longer among patients who cleared mutations; however, this did not reach statistical significance. In addition, alloSCT led to improved RFS irrespective of mutational clearance.


Assuntos
Leucemia Mieloide Aguda , Nucleofosmina , Humanos , Estudos Retrospectivos , Prognóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Mutação , Sequenciamento de Nucleotídeos em Larga Escala/métodos
8.
Leukemia ; 37(7): 1530-1539, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37147425

RESUMO

The Molecular International Prognostic Scoring System (IPSS-M) is a novel risk stratification model for myelodysplastic syndromes (MDS) that builds on the IPSS and IPSS-R by incorporating mutational data. The model showed improved prognostic accuracy over the IPSS-R across three endpoints: overall survival (OS), leukemia-free survival (LFS) and leukemic transformation. This study aimed to validate the findings of the original in a large cohort of MDS patients, as well as assess its validity in therapy-related and hypoplastic MDS. We retrospectively reviewed clinical, cytogenetic and molecular data for 2355 MDS patients treated at the Moffitt Cancer Center. Correlative analysis between IPSS-R and mean IPSS-M scores and outcome predictions was performed on LFS, OS and leukemic transformation. Using the IPSS-M, patients were classified as Very Low (4%), Low (24%), Moderate-Low (14%), Moderate-High (11%), High (19%) and Very-High risk (28%). Median OS was 11.7, 7.1, 4.4, 3.1, 2.3, and 1.3 years from VL to VH risk subgroups. Median LFS was 12.3, 6.9, 3.6, 2.2, 1.4, and 0.5 years respectively. For patients with t-MDS and h-MDS the model retained its prognostic accuracy. Generalized use of this tool will likely result in more accurate prognostic assessment and optimize therapeutic decision-making in MDS.


Assuntos
Leucemia , Síndromes Mielodisplásicas , Humanos , Prognóstico , Estudos Retrospectivos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética
10.
Cancer Chemother Pharmacol ; 91(3): 281-290, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36864346

RESUMO

PURPOSE: Belinostat is an intravenous histone deacetylase inhibitor with approval for T-cell lymphomas. Adavosertib is a first in class oral Wee1 inhibitor. Preclinical studies of the combination demonstrated synergy in various human acute myeloid leukemia (AML) lines as well as AML xenograft mouse models. EXPERIMENTAL DESIGN: This was a phase 1 dose-escalation study of belinostat and adavosertib in patients with relapsed/refractory AML and myelodysplastic syndrome (MDS). Patients received both drugs on days 1-5 and 8-12 of a 21-day cycle. Safety and toxicity were monitored throughout the study. Plasma levels of both drugs were measured for pharmacokinetic analysis. Response was determined by standard criteria including bone marrow biopsy. RESULTS: Twenty patients were enrolled and treated at 4 dose levels. A grade 4 cytokine release syndrome at dose level 4 (adavosertib 225 mg/day; belinostat 1000 mg/m2) qualified as a dose-limiting toxicity event. The most common non-hematologic treatment-related adverse events were nausea, vomiting, diarrhea, dysgeusia, and fatigue. No responses were seen. The study was terminated prior to maximum tolerated dose/recommended phase 2 dose determination. CONCLUSIONS: The combination of belinostat and adavosertib at the tested dose levels was feasible but without efficacy signals in the relapsed/refractory MDS/AML population.


Assuntos
Ácidos Hidroxâmicos , Leucemia Mieloide Aguda , Humanos , Animais , Camundongos , Ácidos Hidroxâmicos/efeitos adversos , Pirimidinonas/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia
11.
Leuk Res ; 124: 106999, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36542963

RESUMO

EZH2 mutations in myeloid neoplasms are loss of function type, and have been linked to poor overall survival (OS) in patients with myelodysplastic syndrome (MDS). However, the specific determinants of outcomes in EZH2-mutant (mut) MDS are not well characterized. In this single-center retrospective study, clinical and genomic data were collected on 1774 patients with MDS treated at Moffitt Cancer Center. In our cohort, 83 (4.7%) patients had a pathogenic EZH2 mutation. Patients with EZH2mut MDS were older than EZH2-wild type (wt) group (median age- 72 vs. 69 years, p = 0.010). The most common co-occurring mutation in EZH2mut MDS was ASXL1, with a significantly higher frequency than EZH2wt (54% vs. 19%, p < 0.001). Patients with EZH2mut MDS had lower response rates to hypomethylating agents compared to EZH2wt MDS (26% vs. 39%; p = 0.050). Median OS of patients with EZH2mut MDS was 30.8 months, with a significantly worse OS than EZH2wt group (35.5 vs. 61.2 months, p = 0.003) in the lower-risk IPSS-R categories. Among patients with EZH2mut MDS, co-presence of ASXL1 or RUNX1 mutations was associated with inferior median OS compared to their wt counterparts (26.8 vs. 48.7 months, p = 0.031). Concurrent chromosome 7 abnormalities (12%) were also associated with significantly worse OS (median OS- 20.8 vs. 35.5 months, p = 0.002) in EZH2mut MDS. Future clinical trials should explore the potential role of novel targeted therapies in improving outcomes in patients with EZH2mut MDS.


Assuntos
Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , Humanos , Idoso , Prognóstico , Estudos Retrospectivos , Síndromes Mielodisplásicas/terapia , Aberrações Cromossômicas , Mutação , Fatores de Transcrição/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética
13.
J Hematol Oncol ; 15(1): 155, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289532

RESUMO

CPX-351 (Europe: Vyxeos® liposomal; United States: Vyxeos®) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. In a phase 3 study in older adults with newly diagnosed, high-risk/secondary AML, CPX-351 improved the remission frequency, overall survival, and post-transplant survival versus 7 + 3. This post hoc analysis evaluated the final 5-year follow-up outcomes according to the European LeukemiaNet 2017 risk classification. CPX-351-treated patients had a higher remission frequency (adverse risk: 41% vs 26%; intermediate risk: 58% vs 39%) and longer median overall survival (adverse risk: 7.59 vs 5.52 months; intermediate risk: 11.86 vs 7.75 months) and post-transplant survival (adverse risk: 43.14 vs 7.08 months; intermediate risk: not reached vs 13.57 months) versus 7 + 3, with outcomes generally poorer among patients with adverse-risk AML. The safety profile of CPX-351 among patients with adverse-risk or intermediate-risk AML was consistent with that of the overall study population. Early mortality was lower, and hospitalization length of stay per patient-year was shorter with CPX-351 versus 7 + 3 within the adverse-risk and intermediate-risk subgroups. The favorable outcomes observed with CPX-351 in this post hoc analysis are consistent with results for the overall study population and further support the use of CPX-351 in these patients.ClinicalTrials.gov Identifier: NCT01696084.


Assuntos
Leucemia Mieloide Aguda , Segunda Neoplasia Primária , Idoso , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/efeitos adversos , Daunorrubicina/efeitos adversos , Segunda Neoplasia Primária/tratamento farmacológico
14.
Cancer ; 128(21): 3880-3887, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36107670

RESUMO

BACKGROUND: Genomic landscape of extramedullary acute myeloid leukemia (EM-AML), including myeloid sarcoma (MS) and leukemia cutis (LC), is not well characterized. The potential utility of next-generation sequencing (NGS) using EM tissue is not established. METHODS: In this multicenter retrospective study, clinical and NGS data were collected on patients with EM-AML. All statistical analyses were performed in SPSS Statistics (v 26). RESULTS: Our study included 58 patients with EM-AML. The median age at diagnosis was 62 years; 59% of patients had MS and 33% had LC. EM-AML was isolated (i.e., without blood or marrow involvement) in 31% and was first noted at relapse in 60% of patients. Median overall survival in our cohort was 18.2 months overall, with 19.1 months and 11.6 months in the newly diagnosed and the relapsed/refractory patients, respectively. At least one targetable or potentially targetable alteration was present in 52% of patients with EM-site NGS, with 26% IDH1, 21% NPM1, 11% IDH2, 6% FLT3, and 13% KMT2A-PTD. Mutations in IDH1 were significantly more prevalent on NGS from EM tissue than non-EM (blood or marrow) samples (26% vs. 3%; p = .030). Three of four patients treated with IDH inhibitors based on EM-site NGS experienced a complete response. CONCLUSIONS: Targetable mutations are frequent in EM-AML and EM-site NGS is warranted for selecting potential targeted therapies for patients with EM-AML.


Assuntos
Isocitrato Desidrogenase , Leucemia Mieloide Aguda , Humanos , Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Prevalência , Prognóstico , Estudos Retrospectivos
15.
Cancer ; 128(19): 3495-3501, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35942592

RESUMO

BACKGROUND: Thrombocytopenia in patients with myelofibrosis (MF) is prognostically detrimental and poses a therapeutic challenge. MF patients with thrombocytopenia are considered high-risk by most prognostic models and their distinct phenotype has given rise to the emerging concept of cytopenic MF. Yet, the mechanisms underlying thrombocytopenia in MF are poorly understood. METHODS: This study aimed to highlight the genetic mechanisms driving low platelet counts in treatment-naive MF patients, establish their phenotypic correlates, and assess prognostic factors specific to this group of patients. RESULTS: The authors found that most patients presenting with low platelets had a clear thrombocytopenia-specific genetic abnormality involving a U2AF1 Q157 mutation, deletion 20q, molecular complexity (three or more mutations), or high-risk karyotype. Etiologic clustering did not correlate with prognosis; however, thrombocytopenic patients were found to have unique prognostic variables including low serum albumin and mutations of SRSF2 and TP53. This led to the proposal of a prognostic model (SRSF2, albumin, TP53 score) that stratifies thrombocytopenic patients as low, intermediate, or high-risk with corresponding median survivals of 93.5, 29.5, and 7.2 months, respectively. CONCLUSIONS: This study demonstrates that thrombocytopenia in MF is driven by different genetic mechanisms and is not uniformly high-risk. As novel agents with improved hematologic safety profiles enter the treatment landscape, thoughtful, risk-adapted therapeutic decisions will be required for MF patients with thrombocytopenia. LAY SUMMARY: A significant minority of patients with myelofibrosis (MF) present with low platelets. Historically, these patients have been viewed as having "high-risk" disease, but this may not be uniformly true. Our study shows that there are various different causes for low platelets in MF, some of which represent high-risk disease whereas others do not. Additionally, our study shows that genetic mutations affecting the genes SRSF2 and TP53 are uniquely problematic in this group, as is a low serum albumin level. This study helps to risk-stratify MF patients with thrombocytopenia, thereby providing more information to guide informed and individualized treatment decisions.


Assuntos
Anemia , Leucopenia , Mielofibrose Primária , Trombocitopenia , Anemia/complicações , Humanos , Mutação , Mielofibrose Primária/complicações , Mielofibrose Primária/genética , Prognóstico , Albumina Sérica , Trombocitopenia/complicações , Trombocitopenia/genética
16.
Br J Haematol ; 198(4): 713-720, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35751140

RESUMO

Splicing factor 3B subunit 1 (SF3B1) somatic mutation in the context of therapy-related myelodysplastic syndromes (t-MDS) has not been well defined. In a large cohort of patients with MDS, those with known SF3B1 somatic mutation were compared as de novo MDS (n = 289) and t-MDS with mutant SF3B1 (SF3B1mut ; n = 31). Baseline characteristics, concomitant mutations, and acute myeloid leukaemia (AML) transformation were similar between the two groups. The median overall survival (OS) of de novo MDS SF3B1mut was significantly longer compared to t-MDS SF3B1mut but not significantly different when adjusted for comorbidities. Comparing t-MDS wild-type SF3B1 (SF3B1WT ; n = 241) to t-MDS SF3B1mut (n = 31), complex cytogenetics were seen in 37.4% versus 10.3% (p = 0.009), tumour protein p53 (TP53) mutation was 36.1% versus 10% (p = 0.004), and AML transformation was 34.4% compared to 12.9% (p = 0.016) respectively. OS was significantly shorter in SF3B1WT versus SF3B1mut . When applying the International Working Group for Prognosis of MDS (IWG-PM) proposed SF3B1 criteria, OS was significantly shorter in SF3B1mut t-MDS compared to de novo MDS SF3B1mut with no significance in AML transformation. Survival was compared between t-MDS SF3B1mut who met the new proposed IWG-PM criteria to t-MDS SF3B1mut who did not meet criteria to survival of SF3B1WT t-MDS. OS was 53 versus 22 and 18 months respectively (p = 0.006). AML transformation was 0%, 26.7% and 32.3% (p = 0.021). Leukaemia-free survival was not reached among the three.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Segunda Neoplasia Primária , Humanos , Leucemia Mieloide Aguda/genética , Mutação , Segunda Neoplasia Primária/genética , Fosfoproteínas/genética , Prognóstico , Fatores de Processamento de RNA/genética , Fatores de Transcrição/genética
18.
JAMA Oncol ; 8(5): 748-754, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35266953

RESUMO

Importance: Patients with cancer experience high rates of morbidity and mortality after SARS-CoV-2 infection. Immune response to mRNA-1273 vaccination across multiple cancer types and treatments remains to be established. Objective: To quantitate antibody responses after mRNA-1273 vaccination among patients with solid tumors and hematologic cancer and to assess clinical and treatment factors associated with vaccine response. Design, Setting, and Participants: This cohort study included patients with cancer who were aged 18 years or older, spoke English or Spanish, had received their first mRNA-1273 dose between January 12 and 25, 2021, and agreed to blood tests before and after vaccination. Exposures: Receipt of 1 and 2 mRNA-1273 SARS-CoV-2 vaccine doses. Main Outcomes and Measures: Seroconversion after each vaccine dose and IgG levels against SARS-CoV-2 spike protein obtained immediately before the first and second vaccine doses and 57 days (plus or minus 14 days) after the first vaccine dose. Cancer diagnoses and treatments were ascertained by medical record review. Serostatus was assessed via enzyme-linked immunosorbent assay. Paired t tests were applied to examine days 1, 29, and 57 SARS-CoV-2 antibody levels. Binding antibody IgG geometric mean titers were calculated based on log10-transformed values. Results: The 515 participants were a mean (SD) age of 64.5 (11.4) years; 262 (50.9%) were women; and 32 (6.2%) were Hispanic individuals and 479 (93.0%) White individuals; race and ethnicity data on 4 (0.7%) participants were missing. Seropositivity after vaccine dose 2 was 90.3% (465; 95% CI, 87.4%-92.7%) among patients with cancer, was significantly lower among patients with hematologic cancer (84.7% [255]; 95% CI, 80.1%-88.6%) vs solid tumors (98.1% [210]; 95% CI, 95.3%-99.5%), and was lowest among patients with lymphoid cancer (70.0% [77]; 95% CI, 60.5%-78.4%). Patients receiving a vaccination within 6 months after anti-CD20 monoclonal antibody treatment had a significantly lower seroconversion (6.3% [1]; 95% CI, 0.2%-30.2%) compared with those treated 6 to 24 months earlier (53.3% [8]; 95% CI, 26.6%-78.7%) or those who never received anti-CD20 treatment (94.2% [456]; 95% CI, 91.7%-96.1%). Low antibody levels after vaccination were observed among patients treated with anti-CD20 within 6 months before vaccination (GM, 15.5 AU/mL; 95% CI, 9.8-24.5 AU/mL), patients treated with small molecules (GM, 646.7 AU/mL; 95% CI, 441.9-946.5 AU/mL), and patients with low lymphocyte (GM, 547.4 AU/mL; 95% CI, 375.5-797.7 AU/mL) and IgG (GM, 494.7 AU/mL; 95% CI, 304.9-802.7 AU/mL) levels. Conclusions and Relevance: This cohort study found that the mRNA-1273 SARS-CoV-2 vaccine induced variable antibody responses that differed by cancer diagnosis and treatment received. These findings suggest that patients with hematologic cancer and those who are receiving immunosuppressive treatments may need additional vaccination doses.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , Formação de Anticorpos , COVID-19 , Neoplasias , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Feminino , Florida , Neoplasias Hematológicas , Humanos , Imunoglobulina G , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Estudos Prospectivos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação
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