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1.
Artigo em Inglês | MEDLINE | ID: mdl-34821176

RESUMO

INTRODUCTION: Ferroptosis, a form of programmed cell death, is mediated primarily by lipid peroxidation via a unique iron-dependent process. The mechanisms of ferroptosis involve the metabolisms of amino acids, irons, and lipids, and the regulation of antioxidant systems. Evidence supports the roles of ferroptosis in cancer, while metabolic reprogramming (a hallmark of cancer) renders tumor cells highly vulnerable to ferroptosis and thus provides a rationale for ferroptosis-targeted therapy for cancer. AREA COVERED: This article examines the current understanding of the mechanisms and related signaling pathways involving ferroptosis; it focuses on novel targets in cancer and its treatment and drug resistance. The development of ferroptosis-targeted therapy, especially in combination with conventional or non-conventional therapies, are considered with dilemmas and key questions in this research area. EXPERT OPINION: An increasing number of potential targets and ferroptosis inducers (FINs) have been identified to treat cancer. However, no specific FIN has entered clinical trials thus far, likely due to poor efficacy and high toxicity in vivo. Thus, new FINs with high selectivity and bioavailability are required to target tumor cells more specifically and potently. Particularly, the combination of FINs with chemotherapy, radiotherapy, targeted therapy, and immunotherapy warrants clinical investigation in the future.

2.
Am J Hematol ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822175

RESUMO

Thromboses are prevalent in POEMS syndrome, but few risk factors for POEMS-associated thrombosis have been identified. The objective of this study is to identify novel risk factors for POEMS-associated thrombosis. In this retrospective cohort of 230 POEMS patients, 27% developed thrombosis. Arterial events were slightly more common than venous. Stroke accounted for 26% of all thromboses and 53% of arterial events. There were differences in baseline features between the thrombosis group and the no thrombosis group, and these were driven by patients with arterial thrombosis. Risk factors for arterial thrombosis included thrombocytosis, elevated hemoglobin/hematocrit, extravascular volume overload and splenomegaly. Hyperprolactinemia appeared to be a risk factor for venous thrombosis. The risk of thrombosis was most striking among men with elevated hemoglobin (32% versus 5%, p < 0.001) and hematocrit (42% versus 5%, p < 0.001) compared to men without. Most thromboses occurred prior to POEMS directed therapy, and most that occurred during therapy happened within 3 months of diagnosis. Twenty-one percent of patients with thrombosis had recurrence. In recognition of high overall rates of thrombosis in this population, all patients with POEMS syndrome should receive prophylactic antiplatelet therapy, and clinicians should consider anticoagulation in patients with risk factors for POEMS-associated thrombosis. This article is protected by copyright. All rights reserved.

3.
Leukemia ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702976

RESUMO

Advances in the understanding of disease biology, drug development, and supportive care have led to improved outcomes in multiple myeloma. Given that these improvements have been reported in clinical trial and referral center populations, questions remain about the generalizability of this observation to patients treated in the community. Contrasting the overall survival experience of 3783 patients seen at Mayo Clinic and 57,654 patients followed in the Surveillance, Epidemiology, and End Results Program (SEER) between 2004 and 2018, we observed different mortality trends across patient populations and subgroups. Early mortality decreased and estimated 5-year overall survival increased over time in both patient populations. Excess mortality (compared to the general population) declined over time in Mayo Clinic patients and remained largely unchanged in SEER patients. Improvements over time were primarily observed in patients with favorable disease characteristics and older patients with multiple myeloma remain a vulnerable population with significant excess mortality compared to the United States general population. Patients with unfavorable disease characteristics have derived disproportionately less benefit from recent advances in the field. Future efforts need to focus on the development of safe and effective therapies for these patients and on increasing timely access to specialized care for patients in the community.

4.
Am J Hematol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34710241

RESUMO

Gain of 1q22 at diagnosis portends poorer outcomes in multiple myeloma (MM), but the prognostic significance of acquired 1q22 gain is unknown. We identified 63 MM patients seen at Mayo Clinic from 1/2004 to 12/2019 without 1q22 gain at diagnosis who acquired it during follow up and compared them to 63 control patients who did not acquire 1q22 gain with similar follow up. We also compared outcomes in the acquired 1q22 gain group with outcomes in 126 patients with 1q22 gain present at diagnosis. The incidence of acquired 1q22 gain was 6.1% (median follow-up 6.8 years); median time to acquisition was 5.0 years (range: 0.7-11.5 years). Abnormalities on baseline fluorescence in situ hybridization (FISH) included trisomies (54%) and monosomy 13 (39%); 16 (25%) had high-risk (HR) translocations or del(17p). Median progression-free survival with front line therapy was 29.5 months in patients with acquired 1q22 gain, versus 31.4 months in control patients (p = .34) and 31.2 months in patients with de novo 1q22 gain (p = .04). Median overall survival (OS) from diagnosis was 10.9 years in patients with acquired 1q22 gain, versus 13.0 years in control patients (p = .03) and 6.3 years in patients with de novo 1q22 gain (p = .01). Presence of HR FISH at baseline increased risk of 1q22 gain acquisition. We demonstrate that acquisition of 1q22 gain is a significant molecular event in MM, associated with reduced OS. Among HR patients for whom this clonal evolution is determined, a risk-adapted approach and/or clinical trial should be considered.

5.
Am J Hematol ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34661922

RESUMO

Patients with multiple myeloma who are refractory to currently available effective therapies have short expected survival. Modalities harvesting the knowledge of the immune characteristics and microenvironment of myeloma such as chimeric antigen receptor (CAR) T-lymphocytes, bispecific antibodies (bsAbs), and antibody-drug conjugates (ADCs) have shown potential in early phase trials. Based on data from phase 2 studies, idecabtagene vicleucel (ide cel), an anti-B-cell maturation antigen CAR T-product and belantamab mafodotin (belamaf), an ADC are currently approved in the relapsed/refractory setting. bsAbs have shown promise with quick and deep responses. In this review, we summarize the available evidence on these treatments from clinical trials.

6.
Lancet Oncol ; 22(11): 1582-1596, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34655533

RESUMO

BACKGROUND: In the primary analysis of the phase 3 MAIA trial (median follow-up 28·0 months), a significant improvement in progression-free survival was observed with daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in transplantation-ineligible patients with newly diagnosed multiple myeloma. Here, we report the updated efficacy and safety results from a prespecified interim analysis for overall survival. METHODS: MAIA is an ongoing, multicentre, randomised, open-label, phase 3 trial that enrolled patients at 176 hospitals in 14 countries across North America, Europe, the Middle East, and the Asia-Pacific region. Eligible patients were aged 18 years or older, had newly diagnosed multiple myeloma, had an Eastern Cooperative Oncology Group performance status score of 0-2, and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation because of their age (≥65 years) or comorbidities. Patients were randomly assigned (1:1) using randomly permuted blocks (block size 4) by an interactive web response system to receive 28-day cycles of intravenous daratumumab (16 mg/kg, once per week during cycles 1-2, once every 2 weeks in cycles 3-6, and once every 4 weeks thereafter) plus oral lenalidomide (25 mg on days 1-21 of each cycle) and oral dexamethasone (40 mg on days 1, 8, 15, and 22 of each cycle; daratumumab group) or lenalidomide and dexamethasone alone (control group). Randomisation was stratified by International Staging System disease stage, geographical region, and age. Neither patients nor investigators were masked to treatment assignment. The primary endpoint was progression-free survival, which was centrally assessed, and a secondary endpoint was overall survival (both assessed in the intention-to-treat population). The safety population included patients who received at least one dose of the study treatment. The results presented here are from a prespecified interim analysis for overall survival, for which the prespecified stopping boundary was p=0·0414. This trial is registered with ClinicalTrials.gov, NCT02252172. FINDINGS: Between March 18, 2015, and Jan 15, 2017, 952 patients were assessed for eligibility, of whom 737 patients were enrolled and randomly assigned to the daratumumab group (n=368) or the control group (n=369). At a median follow-up of 56·2 months (IQR 52·7-59·9), median progression-free survival was not reached (95% CI 54·8-not reached) in the daratumumab group versus 34·4 months (29·6-39·2) in the control group (hazard ratio [HR] 0·53 [95% CI 0·43-0·66]; p<0·0001). Median overall survival was not reached in either group (daratumumab group, 95% CI not reached-not reached; control group, 95% CI 55·7-not reached; HR 0·68 [95% CI 0·53-0·86]; p=0·0013). The most common (>15%) grade 3 or higher treatment-emergent adverse events were neutropenia (197 [54%] patients in the daratumumab group vs 135 [37%] patients in the control group), pneumonia (70 [19%] vs 39 [11%]), anaemia (61 [17%] vs 79 [22%]), and lymphopenia (60 [16%] vs 41 [11%]). Serious adverse events occurred in 281 (77%) patients in the daratumumab group and 257 (70%) patients in the control group. Treatment-related deaths occurred in 13 (4%) patients in the daratumumab group and ten (3%) patients in the control group. INTERPRETATION: Daratumumab plus lenalidomide and dexamethasone increased overall survival and progression-free survival in patients ineligible for stem-cell transplantation with newly diagnosed multiple myeloma. There were no new safety concerns. Our results support the frontline use of daratumumab plus lenalidomide and dexamethasone for patients with multiple myeloma who are ineligible for transplantation. FUNDING: Janssen Research & Development.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/uso terapêutico , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Masculino , Intervalo Livre de Progressão , Taxa de Sobrevida
7.
Expert Rev Hematol ; : 1-16, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34551651

RESUMO

INTRODUCTION: Multiple myeloma (MM) remains an incurable disease with a median overall survival of approximately 5 years. Gain or amplification of 1q21 (1q21+) occurs in around 40% of patients with MM and generally portends a poor prognosis. Patients with MM who harbor 1q21+ are at increased risk of drug resistance, disease progression, and death. New pharmacotherapies with novel modes of action are required to overcome the negative prognostic impact of 1q21+. Areas covered: This review discusses the detection, biology, prognosis, and therapeutic targeting of 1q21+ in newly diagnosed and relapsed MM. Patients with MM and 1q21+ tend to present with higher tumor burden, greater end-organ damage, and more co-occurring high-risk cytogenetic abnormalities than patients without 1q21+. The chromosomal rearrangements associated with 1q21+ result in dysregulation of genes involved in oncogenesis. Identification and characterization of the 1q21+ molecular targets are needed to inform on prognosis and treatment strategy. Clinical trial data are emerging that addition of isatuximab to combination therapies may improve outcomes in patients with 1q21+ MM. Expert opinion: In the next 5 years, the results of ongoing research and trials are likely to focus on the therapeutic impact and treatment decisions associated with 1q21+ in MM.

8.
Blood Adv ; 5(19): 3748-3759, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34470049

RESUMO

Proteins in the antiapoptotic B-cell lymphoma 2 (BCL-2) family play a role in the pathophysiology of multiple myeloma (MM). Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis of MM cells, and its efficacy may be potentiated through combination with agents that increase BCL-2 dependency or have complementary mechanisms of action. The safety, tolerability, pharmacokinetics, and antitumor activity of venetoclax in combination with carfilzomib and dexamethasone (VenKd) in adults with relapsed/refractory MM (RRMM) were investigated in this phase 2 dose-escalation study. Oral venetoclax (400 or 800 mg) was administered daily in combination with intravenous carfilzomib (27, 56, or 70 mg/m2) and oral dexamethasone (20 or 40 mg) in 4 dose-finding cohorts. The expansion cohort received venetoclax 800 mg, carfilzomib 70 mg/m2, and dexamethasone 40 mg. Forty-nine patients received treatment. Median prior lines of therapy was 1 (range, 1-3), and median time in the study was 27 months. The most common treatment-emergent adverse events were diarrhea (65%), fatigue (47%), nausea (47%), and lymphopenia (35%). Serious adverse events occurred in 26 (53%) patients. Of 3 treatment-emergent deaths, 1 was considered treatment related. The overall response rate was 80% in all patients, 92% in patients with t(11;14) (n = 13), and 75% in patients without (n = 36). The rate of complete response or better was 41%. Median progression-free survival was 22.8 months. Treatment with VenKd was well tolerated and showed promising response rates in this RRMM patient population, with greater responses observed in patients with t(11;14). This trial is registered at www.clinicaltrials.gov as #NCT02899052.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes , Dexametasona/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos , Sulfonamidas
9.
Blood Rev ; : 100872, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34384602

RESUMO

Dysregulation of DNA methylation in B cells has been observed during their neoplastic transformation and therefore closely associated with various B-cell malignancies including multiple myeloma (MM), a malignancy of terminally differentiated plasma cells. Emerging evidence has unveiled pronounced alterations in DNA methylation in MM, including both global and gene-specific changes that can affect genome stability and gene transcription. Moreover, dysregulated expression of DNA methylation-modifying enzymes has been related with myelomagenesis, disease progression, and poor prognosis. However, the functional roles of the epigenetic abnormalities involving DNA methylation in MM remain elusive. In this article, we review current understanding of the alterations in DNA methylome and DNA methylation modifiers in MM, particularly focusing on DNA methyltransferases (DNMTs) and tet methylcytosine dioxygenases (TETs). We also discuss how these DNA methylation modifiers may be regulated and function in MM cells, therefore providing a rationale for developing novel epigenetic therapies targeting DNA methylation in MM.

10.
Clin Cancer Res ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321279

RESUMO

The development of novel agents has transformed the treatment paradigm for multiple myeloma (MM), with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in MM patients. Complementary liquid biopsy-based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid-based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory MM, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in MM is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes.

11.
Clin Cancer Res ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233962

RESUMO

PURPOSE: Structural variants (SV) of the MYC gene region are common in multiple myeloma and influence disease progression. However, the prognostic significance of different MYC SVs in multiple myeloma has not been clearly established. EXPERIMENTAL DESIGN: We conducted a retrospective study of multiple myeloma comparing MYC SV subtypes identified by next-generation sequencing (NGS) and FISH to MYC expression and disease survival using 140 cases from Mayo Clinic and 658 cases from the MMRF CoMMpass study. RESULTS: MYC SVs were found in 41% of cases and were classified into nine subtypes. A correlation between the presence of a MYC SV and increased MYC expression was identified. Among the nine MYC subtypes, the non-immunoglobulin (non-Ig) insertion subtype was independently associated with improved outcomes, while the Ig insertion subtype, specifically involving the IgL gene partner, was independently associated with poorer outcomes compared with other MYC SV subtypes. Although the FISH methodology failed to detect approximately 70% of all MYC SVs, those detected by FISH were associated with elevated MYC gene expression and poor outcomes suggesting a different pathogenic role for FISH-detected MYC subtypes compared with other MYC subtypes. CONCLUSIONS: Understanding the impact of different MYC SVs on disease outcome is necessary for the reliable interpretation of MYC SVs in multiple myeloma. NGS approaches should be considered as a replacement technique for a more comprehensive evaluation of the multiple myeloma clone.

12.
Blood ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269818

RESUMO

In patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab reduced the risk of disease progression or death by 44% in MAIA (daratumumab/lenalidomide/dexamethasone; D-Rd) and 58% in ALCYONE (daratumumab/bortezomib/melphalan/prednisone; D-VMP). Minimal residual disease (MRD) is a sensitive measure of disease and response to therapy. MRD-negativity status and durability were assessed in MAIA and ALCYONE. MRD assessments using next-generation sequencing (10-5) occurred for patients achieving complete response (CR) or better, and after ≥CR at 12, 18, 24, and 30 months from the first dose. Progression-free survival (PFS) by MRD status and sustained MRD negativity lasting ≥6 and ≥12 months were analyzed in the intent-to-treat population and among patients achieving ≥CR. In MAIA, (D-Rd, n=368; Rd, n=369), and ALCYONE (D-VMP, n=350; VMP, n=356), the median duration of follow-up was 36.4 months and 40.1 months, respectively. MRD-negative status and sustained MRD negativity lasting ≥6 and ≥12 months were associated with improved PFS, regardless of treatment group. However, daratumumab-based therapy improved rates of MRD negativity lasting ≥6 months (D-Rd, 14.9% vs Rd, 4.3%; D-VMP, 15.7% vs VMP, 4.5%) and ≥12 months (D-Rd, 10.9% vs Rd, 2.4%; D-VMP, 14.0% vs VMP, 2.8%), both of which translated to improved PFS versus control groups. In a pooled analysis, patients who were MRD negative had improved PFS versus patients who were MRD positive. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes. ClinicalTrials.gov identifier NCT02252172 (MAIA); NCT02195479 (ALCYONE).

13.
Blood ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289038

RESUMO

We explored minimal residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM) using data from four phase 3 studies (POLLUX, CASTOR, ALCYONE, and MAIA). Each study previously demonstrated that daratumumab-based therapies improved MRD-negativity rates and reduced the risk of disease progression or death by approximately half versus standards of care. We conducted a large-scale pooled analysis for associations between patients achieving complete response (CR) or better with MRD-negative status, and progression-free survival (PFS). MRD was assessed via next-generation sequencing (10‒5 threshold). Patient-level data were pooled from all four studies, and for patients with TIE NDMM plus patients with RRMM who received ≤2 prior lines of therapy (≤2PL). PFS was evaluated by response and MRD status. Median follow-up (months) was: POLLUX, 54.8; CASTOR, 50.2; ALCYONE, 40.1; and MAIA, 36.4. Patients who achieved ≥CR and MRD negativity had improved PFS versus those who failed to reach CR or were MRD positive (TIE NDMM and RRMM hazard ratio [HR] 0.20, P < .0001; TIE NDMM and RRMM ≤2PL HR 0.20, P < .0001). This benefit occurred irrespective of therapy or disease setting. A time-varying Cox proportional hazard model confirmed that ≥CR with MRD negativity was associated with improved PFS. Daratumumab-based treatment was associated with more patients reaching ≥CR and MRD negativity. These findings represent the first large-scale analysis with robust methodology to support ≥CR with MRD negativity as a prognostic factor for PFS in RRMM and TIE NDMM. These trials were registered at www.ClinicalTrials.gov: NCT02076009/NCT02136134/NCT02195479/NCT02252172.

14.
Clin Cancer Res ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315721

RESUMO

The multiple myeloma treatment landscape has evolved considerably over the last 20 years with the development of multiple therapies with novel mechanisms of action and new combination regimens. However, the recent failure of several large phase III trials, coupled with an increased understanding of the mutational landscape of multiple myeloma has provided opportunities to explore optimal strategies for future multiple myeloma drug development. The Office of Oncologic Diseases at the FDA held an educational symposium, "Drug Development in MM-Project 2025," in November 2019. The symposium brought together select U.S.-based academic thought leaders in the field of multiple myeloma to explore issues relevant to regulatory science in the field, including considerations for trial design, combination strategies, control arms, and precision medicine. This article summarizes the highlights of this educational symposium held at the FDA, including discussions on the future development of novel drugs and drug combinations and biomarker-directed therapies for patients with multiple myeloma.

15.
Leuk Lymphoma ; 62(12): 3011-3018, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34263694

RESUMO

This is a retrospective study of patients with multiple myeloma (MM) who were >75 years old. We identified 394 patients and for non-trial patients (n = 350), immunomodulatory drug (IMiD)+dex (32%) was the most commonly used regimen followed by alkylator with steroids or other therapy (21%), alkylator + proteasome inhibitor (PI)+steroid (18%), and IMiD + PI + dex (13%). Overall, achieving ≥ very good partial response was more in patients receiving a triplet compared to other therapies (46% vs. 21%, p < 0.0001). Also, the median overall survival (OS) was significantly longer in patients who were treated with a triplet (median OS: 50.2 vs. 32.8 months, p = 0.0006). In a multivariate for OS, receiving a triplet (HR: 0.65, p = 0.02), not having an R-ISS stage 3 (HR: 0.36, p = 0.0003), and bone marrow plasma cell percentage <60% (HR: 0.69, p = 0.03) were predictive. In conclusion, being able to receive triplet therapy was associated with better survival in our MM patients >75 years old.

16.
Am J Hematol ; 96(9): 1131-1136, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34115387

RESUMO

Multiple myeloma (MM) remains an incurable disease despite incorporation of novel agents. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor is approved for some hematologic malignancies but not yet for MM, although clinical trials have shown efficacy in patients with MM, particularly those harboring t(11;14). We reviewed the medical records of relapsed and/or refractory MM patients to study the efficacy and safety of venetoclax used outside of clinical trials at Mayo Clinic between December, 2016 and March, 2019. The data cut-off date was August 06, 2020. We identified 56 patients of whom 42 (75%) harbored t(11;14). The median number of prior therapies was six (range 1-15) and 14% of patients had received ≥10 prior lines of therapy. Fifty-three (95%) patients were refractory to an immunomodulatory drug and proteasome inhibitor. Venetoclax was used as monotherapy or doublet, in combination with dexamethasone in 55% (n = 31) and a triplet or quadruplet in 45% of patients. No patient experienced tumor lysis syndrome. Overall response rate in 52 evaluable patients was 44%. The median time to best response was 2 months and median duration of response was 13.6 months. The median PFS for the entire cohort was 5.8 (95% CI 4.9-10.3) months and median OS was 28.4 (95% CI 14.6-not reached) months. The presence of t(11;14) was associated with improved PFS (median 9.7 months vs. 4.2 months, p = 0.019) and OS (median not reached vs. 10.8 9 months, p = 0.015). Venetoclax demonstrates encouraging activity in heavily-treated patients with relapsed/refractory MM, particularly the t(11;14) patient-population.


Assuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Sulfonamidas/efeitos adversos , Resultado do Tratamento
18.
Mayo Clin Proc ; 96(6): 1546-1577, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34088417

RESUMO

Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressive and life-threatening organ failure. The heart and the kidneys are the most commonly involved organs, but almost any organ can be involved. Because of the nonspecific presentation, diagnosis delay is common, and many patients are diagnosed with advanced organ failure. In the era of effective therapies and improved outcomes for patients with AL amyloidosis, the importance of early recognition is further enhanced as the ability to reverse organ dysfunction is limited in those with a profound organ failure. As AL amyloidosis is an uncommon disorder and given patients' frailty and high early death rate, management of this complex condition is challenging. The treatment of AL amyloidosis is based on various anti-plasma cell therapies. These therapies are borrowed and customized from the treatment of multiple myeloma, a more common disorder. However, a growing number of phase 2/3 studies dedicated to the AL amyloidosis population are being performed, making treatment decisions more evidence-based. Supportive care is an integral part of management of AL amyloidosis because of the inherent organ dysfunction, limiting the delivery of effective therapy. This extensive review brings an updated summary on the management of AL amyloidosis, sectioned into the 3 pillars for survival improvement: early disease recognition, anti-plasma cell therapy, and supportive care.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Mieloma Múltiplo/terapia , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Medição de Risco
20.
Adv Ther ; 38(7): 3694-3711, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34145483

RESUMO

Multiple Myeloma (MM) is part of a spectrum of plasma cell disorders that may result in end organ damage. MM is subclassified into high and standard risk based on cytogenetic and laboratory markers. The treatment of newly diagnosed multiple myeloma is constantly changing with the advent of novel therapies. Recent advances in therapies have resulted in longer time to remission and overall survival. the introduction of targeted therapy with monoclonal antibodies such as Daratumumab has improved stringent complete response to 39%. In this review, we outline the current approach to diagnosis, prognosis, and management of newly diagnosed multiple myeloma in both transplant eligible and ineligible patients.


Assuntos
Antineoplásicos Imunológicos , Mieloma Múltiplo , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico
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