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Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.
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Anticuerpos Biespecíficos , Antineoplásicos , Linfoma de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Inducción de Remisión , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Anticuerpos Biespecíficos/efectos adversos , Linfoma de Células B/tratamiento farmacológico , Respuesta Patológica Completa , Enfermedad Aguda , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Antineoplásicos/efectos adversosRESUMEN
BACKGROUND: Acute myeloid leukemia (AML) is a disease of the hematopoietic system that remains a therapeutic challenge despite advances in our understanding of the underlying cancer biology in the past decade. It is also an affliction of the elderly that predominantly affects patients over 60 years of age. Standard therapy involves intensive chemotherapy that is often difficult to tolerate in older populations. Fortunately, recent developments in molecular targeting have shown promising results in treating leukemia, paving the way for novel treatment strategies that are easier to tolerate. SUMMARY: Venetoclax, a BCL-2 inhibitor, when combined with a hypomethylating agent, has proven to be a highly effective and well-tolerated drug and established itself as a new standard for treating AML in patients who are unfit for standard intensive therapy. Other targeted therapies include clinically proven and FDA-approved agents, such as IDH1/2 inhibitors, FLT3 inhibitors, and Gemtuzumab, as well as newer and more experimental drugs such as magrolimab, PI-kinase inhibitors, and T-cell engaging therapy. Some of the novel agents such as magrolimab and menin inhibitors are particularly promising, providing therapeutic options to a wider population of patients than ever before. Determining who will benefit from intense or novel low-intense therapy remains a challenge, and it requires careful assessment of individual patient's fitness and disease characteristics. KEY MESSAGES: This article reviews past and current treatment strategies that harness various mechanisms of leukemia-targeting agents and introduces novel therapies on the horizon aimed at exploring therapeutic options for the elderly and unfit patient population. It also provides a strategy to select the best available therapy for elderly patients with both newly diagnosed and relapsed/refractory AML.
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Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Anciano , Persona de Mediana Edad , Antineoplásicos/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/etiología , Inhibidores de Proteínas Quinasas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
T-cell lymphomas are rare and aggressive malignancies associated with poor outcome, often because of the development of resistance in the lymphoma against chemotherapy as well as intolerance in patients to the established and toxic chemotherapy regimens. In this review article, we discuss the epidemiology, pathophysiology, current standard of care, and future treatments of common types of T-cell lymphomas, including adult T-cell leukemia/lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large-cell lymphoma, aggressive NK/T-cell lymphoma, and cutaneous T-cell lymphoma.
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Linfoma de Células T/epidemiología , Linfoma de Células T/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Humanos , Células Asesinas Naturales/patología , Linfoma de Células T/patología , Prednisona/uso terapéutico , Trasplante de Células Madre/métodos , Trasplante Homólogo , Vincristina/uso terapéuticoRESUMEN
BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.
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Leucemia Mieloide Aguda , Infiltración Leucémica , Humanos , Femenino , Persona de Mediana Edad , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/complicaciones , Infiltración Leucémica/patología , Resultado Fatal , Recurrencia , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapiaRESUMEN
CONTEXT: Compared to patients with solid malignancies, less is known about the role of palliative care in patients with hematologic malignancies, leading to underutilization of palliative care. OBJECTIVES: Evaluate the timing and impact of palliative care referrals on end-of-life outcomes over a 5-year period with intent to improve the utilization of palliative care in patients with advanced hematologic malignancies. METHODS: A retrospective cohort of patients from an urban, NCI-designated comprehensive cancer center, aged 18 years and older with a diagnosis of an advanced hematologic malignancy were separated into groups of early, late, very late, or no specialty palliative care. Logistic regression models were constructed to examine variables associated with timing of palliative care referral. Groups were compared using the Kruskal Wallis test and Dunn's test with a Bonferroni correction method. RESULTS: 222 patients with advanced hematologic malignancies who died between July 1, 20218 and June 30, 2023 were included. 50 (23%), 41 (18%), and 51 (23%) patients received an early, late, and very late palliative care referral, respectively and 80 (36%) patients did not receive a palliative care referral. There was a significantly high completion of ACP documentation among the palliative care cohorts. There was no significant difference among all cohorts in end-of-life outcomes in the last 14 or 30 days of life. CONCLUSION: ACP documentation improved with palliative care, however, end-of-life outcomes did not. These results are likely due to the majority of late, inpatient palliative care referrals. Future studies with targeted interventions are needed to improve these outcomes.
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Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ-67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first-in-human, open-label, phase I, dose-escalation/dose-expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ-67571244 was administered intravenously or subcutaneously using step-up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose-escalation cohorts (n = 68) and before starting dose-expansion. Overall, 11 (16.2%) patients experienced ≥1 dose-limiting toxicity; all experienced ≥1 treatment-emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ-67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion-related reactions, and elevated liver function tests. A prolonged step-up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T-cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ-67571244 efficacy was not achieved, thus MTD and RP2D were not determined.
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Antineoplásicos , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Antineoplásicos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Lectina 3 Similar a Ig de Unión al Ácido Siálico/inmunologíaRESUMEN
Reducing the incidence of graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (HSCT) is warranted. Posttransplant cyclophosphamide (PTCy) is the main agent used for GVHD prevention in this setting. It remains unknown whether costimulation blockade can be safely combined with PTCy and enhance its efficacy. We performed a phase 1b-2 clinical trial to examine the combination of PTCy, abatacept, and a short course of tacrolimus (CAST) after peripheral blood haploidentical HSCT. The primary end point was the incidence of grades 2-4 acute GVHD by day +120. The study enrolled 46 patients with a median age of 60 years (range, 18-74 years). The cumulative incidences of grades 2-4 and 3 or 4 acute GVHD were 17.4% (95% confidence interval [CI], 9.2-32.9) and 4.4% (95% CI, 1.1-17.1), respectively. With a median follow-up of 15.3 months, the cumulative incidence of 1-year treatment-related mortality was 4.4% (95% CI, 1.1-17.1). The estimated 1-year moderate-to-severe chronic GVHD rate, relapse rate, progression-free survival, overall survival, and GVHD- and relapse-free survival were 15.9% (95% CI, 8-31.7), 11.7% (95% CI, 5-27.2), 84.1% (95% CI, 73.8-95.7), 85.9% (95% CI, 75.9-97.2), and 66.1% (95% CI, 53.4-81.8), respectively. Toxicities were similar to those expected in patients receiving haploidentical HSCT. This clinical trial showed that the CAST regimen is safe and effective in reducing the rate of grades 2-4 acute GVHD after haploidentical peripheral blood HSCT. This trial was registered at www.clinicaltrials.gov as #NCT04503616.
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Enfermedad Injerto contra Huésped , Tacrolimus , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Tacrolimus/uso terapéutico , Abatacept/uso terapéutico , Trasplante Haploidéntico , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/tratamiento farmacológicoRESUMEN
BACKGROUND: Large granular lymphocytic leukemia is a rare lymphocytic neoplasm that can pose a treatment challenge in patients with severe neutropenia in whom conventional therapies fail. We report one of the first cases in which allogeneic stem cell therapy was used as treatment for large granular lymphocytic leukemia. We report and discuss the case of a 42-year-old white Caucasian female who, despite multiple therapies including methotrexate, cyclophosphamide, prednisone, cyclosporine, and pentostatin, continued to show severe neutropenia and recurrent infections. The patient was treated successfully and cured by allogeneic stem cell transplant without any major complications. CONCLUSIONS: The significant importance of this case report is the introduction of a new treatment algorithm for challenging cases of T-cell large granular lymphocytic leukemia in which standard care fails. We hope that this case report will raise awareness of the potential benefits of allogeneic stem cell transplant in the treatment of aggressive forms of T-cell large granular lymphocytic leukemia.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Granular Grande , Adulto , Femenino , Humanos , Leucemia Linfocítica Granular Grande/terapia , Neutropenia/complicaciones , Neutropenia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
PURPOSE: The recruitment of underserved patients into therapeutic oncology trials is imperative. The National Institutes of Health mandates the inclusion of minorities in clinical research, although their participation remains under-represented. Institutions have used data mining to match patients to clinical trials. In a public health care system, such expensive tools are unavailable. METHODS: The NYU Clinical Trials Office implemented a quality improvement program at Bellevue Hospital Cancer Center to increase therapeutic trial enrollment. Patients are screened through the electronic medical record, tumor board conferences, and the cancer registry. Our analysis evaluated two variables: number of patients identified and those enrolled into clinical trials. RESULTS: Two years before the program, there were 31 patients enrolled. For a period of 24 months (July 2017 to July 2019), we identified 255 patients, of whom 143 (56.1%) were enrolled. Of those enrolled, 121 (84.6%) received treatment, and 22 (15%) were screen failures. Fifty-five (38.5%) were referred to NYU Perlmutter Cancer Center for therapy. Of the total enrollees, 64% were female, 56% were non-White, and overall median age was 55 years (range: 33-88 years). Our participants spoke 16 different languages, and 57% were non-English-speaking. We enrolled patients into eight different disease categories, with 38% recruited to breast cancer trials. Eighty-three percent of our patients reside in low-income areas, with 62% in both low-income and Health Professional Shortage Areas. CONCLUSION: Prescreening at Bellevue has led to a 4.6-fold increase in patient enrollment to clinical trials. Future research into using prescreening programs at public institutions may improve access to clinical trials for underserved populations.
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Oncología Médica , Neoplasias , Instituciones Oncológicas , Femenino , Hospitales Públicos , Humanos , Área sin Atención Médica , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/terapia , Estados Unidos/epidemiologíaRESUMEN
We present the case of a 56-year-old female with a diagnosis of acute T-cell lymphoblastic leukemia who received myeloablative conditioning for bone marrow transplant with total body irradiation (TBI) using volumetric modulated arc therapy (VMAT) to the upper body and anterior-posterior/posterior-anterior (AP/PA) open fields to the lower body followed by hematopoietic stem cell transplant. Her clinical course was complicated by high-grade pulmonary toxic effects 55 days after treatment that resulted in death. We discuss the case, planning considerations by radiation oncologists and radiation physicists, and the multidisciplinary medical management of this patient.
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Radioterapia de Intensidad Modulada , Irradiación Corporal Total , Humanos , Femenino , Persona de Mediana Edad , Irradiación Corporal Total/efectos adversos , Irradiación Corporal Total/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Vidarabina/efectos adversos , Estudios RetrospectivosRESUMEN
Allogeneic hematopoietic cell transplant (Allo-HCT) is a potentially curative therapy for many malignant and nonmalignant hematological diseases. However, a suitable human leukocyte antigens (HLAs)-matched donor may not be available when the patient is in urgent need of a stem cell transplant. This challenge has been ameliorated to a large extent by the introduction of haploidentical donors. This type of donor shares one HLA haplotype with the recipient. Therefore, a patient's full sibling has a 50% chance of being haploidentical and a patient's biologic parents and children will all be haploidentical, thus providing an immediately accessible, motivated donor for almost every recipient. Haploidentical transplants previously incurred prohibitively poor outcomes, preventing their widespread use. However, several recent advances have dramatically improved the results, making them a more viable donor source. In this review, we discuss different types of donors used for Allo-HCT with a particular focus on the use of haploidentical donors and their future potential.
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Following allogeneic blood and marrow transplantation (BMT), graft-versus-host disease (GvHD) continues to represent a significant cause of treatment failure, despite the routine use of conventional, mainly calcineurin inhibitor-based prophylaxis. Recently, post-transplant cyclophosphamide (PTCy) has emerged as a safe and efficacious alternative. First, omitting the need for ex vivo T-cell depletion in the setting of haploidentical transplantation, growing evidence supports PTCy role in GvHD prevention in matched-related and matched-unrelated transplants. Through improved understanding of GvHD pathophysiology and advancements in drug development, PTCy emerges as a unique opportunity to design calcineurin inhibitor-free strategies by integrating agents that target different stages of GvHD development.
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Trasplante de Médula Ósea , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Animales , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA/genética , Antígenos HLA/metabolismo , Histocompatibilidad , Prueba de Histocompatibilidad , Humanos , Trasplante Haploidéntico , Donante no EmparentadoRESUMEN
Graft-versus-host disease (GvHD) in its acute and chronic forms continues to represent a significant barrier to the success and wide-applicability of blood and marrow transplantation as a potentially curative treatment modality for a number of benign and malignant blood conditions. Presently, calcineurin inhibitor (CNI)-based regimens remain the most commonly used prevention strategy, although post-transplant cyclophosphamide is emerging as an alternative approach, and is providing a backbone for innovative CNI-free combinations. In this paper, we review the current strategies used for the prevention of GvHD, and highlight some of the developing and promising combinations.
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Human herpesvirus-6 (HHV-6) is a highly prevalent virus that establishes lifelong latency in human hosts. Symptomatic HHV-6 reactivation rarely occurs in immunocompetent individuals and is best described in immunosuppressed patients such as recipients of bone marrow transplants (BMT). In that setting, HHV-6 reactivation has been associated with fever, rash, pneumonitis, encephalitis, and delayed engraftment. While these complications are well documented in allogeneic transplant, the clinical impact of such reactivation is not well known in autologous BMT. We described a case of HHV-6-associated encephalitis in a previously heavily treated patient with multiple myeloma (MM) following a second autologous BMT, and discuss the need for clinicians to be aware of the potential clinical impact of HHV-6 following autologous BMT in the era of immunomodulatory agents.
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BACKGROUND: Primary plasmacytomas are localized proliferations of clonal plasma cells occurring in the absence of a systemic plasma cell dyscrasia such as multiple myeloma. Primary plasmacytomas most commonly manifest as solitary lesions of the bone or of the upper aerodigestive tract. Presentation in a lymph node is very uncommon and can often be initially mistaken for lymphoma. Because they are local phenomena, primary plasmacytomas are managed with local therapies such as radiation or, less commonly, excision. Multifocal presentations are rare and are often not amenable to local treatment modalities, thus requiring systemic therapies. Because of their rarity, standardized treatment guidelines are not established, and treatment paradigms borrow heavily from those employed in multiple myeloma. Multifocal presentation in lymph nodes is nearly unheard of with only seven such cases reported in the existing literature, only four of which were diffuse enough to require systemic therapy. Here we describe the most diffuse and widely distributed instance of primary lymph node plasmacytoma yet reported and present a description of its successful treatment with systemic therapy. CASE PRESENTATION: A 71-year-old Asian man presented with progressive fatigue in the setting of diffuse hypermetabolic lymphadenopathy throughout his chest, abdomen, and pelvis. A diagnosis of lymphoma was initially suspected; however, a lymph node biopsy was consistent with plasmacytoma. A bone marrow biopsy was unremarkable, and no monoclonal protein was identified, establishing a diagnosis of primary extramedullary plasmacytomas of the lymph nodes. He was treated with a myeloma-like regimen consisting of four cycles of bortezomib/dexamethasone followed by two cycles of thalidomide/prednisone with improvement in symptoms and near complete resolution of prior hypermetabolic lymphadenopathy. He remains in remission over 18 months following completion of therapy. CONCLUSION: This case report and accompanying literature review highlight the exceedingly rare and easily misclassified entity of primary plasmacytoma of diffuse lymph nodes. Importantly, we demonstrate that this entity may be treated with, and demonstrate excellent response to, systemic therapies often employed in multiple myeloma.
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Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Ganglios Linfáticos/patología , Linfadenopatía/patología , Plasmacitoma/patología , Prednisona/uso terapéutico , Talidomida/uso terapéutico , Anciano , Fatiga , Humanos , Linfadenopatía/tratamiento farmacológico , Masculino , Células Plasmáticas/patología , Plasmacitoma/tratamiento farmacológico , Inducción de RemisiónRESUMEN
IMPORTANCE: Anti-PD-1 (anti-programmed cell death 1) and anti-PD-L1 (anti-programmed cell death ligand 1) regimens are preferred therapies for many cancers, including cancers associated with HIV. However, patients with HIV were excluded from most registered trials. OBJECTIVE: The primary objective was to evaluate the safety of pembrolizumab in people with HIV and advanced cancer; the secondary objective was to evaluate tumor responses. DESIGN, SETTING, AND PARTICIPANTS: Open-label, nonrandomized, phase 1 multicenter study conducted at 7 Cancer Immunotherapy Trials Network sites. Patients with HIV and advanced cancer as well as a CD4 count greater than or equal to 100 cells/µL, antiretroviral therapy (ART) for 4 or more weeks, and an HIV viral load of less than 200 copies/mL were eligible. Exclusion criteria included uncontrolled hepatitis B or C infection, active immunosuppressive therapy, or a history of autoimmune disease requiring systemic therapy. INTERVENTIONS: Pembrolizumab, 200 mg, administered intravenously every 3 weeks for up to 35 doses in 3 CD4 count-defined cohorts. Participants continued ART. MAIN OUTCOMES AND MEASURES: Safety and tolerability were assessed using current NCI Common Terminology Criteria for Adverse Events. Immune-related adverse events grade 2 or higher were considered immune-related events of clinical interest (irECI). Tumor responses were evaluated using standard tumor-specific criteria. RESULTS: Thirty participants (28 men and 2 women; median [range] age, 57 [39-77] years) were enrolled from April 2016 through March 2018; 6 had Kaposi sarcoma (KS), 5 had non-Hodgkin lymphoma (NHL), and 19 had non-AIDS-defining cancers. Safety was observed over 183 cycles of treatment with pembrolizumab. Most treatment-emergent adverse events at least possibly attributed to pembrolizumab were grade 1 or 2 (n = 22), and 20% (n = 6) were grade 3. The irECI included hypothyroidism (6 participants), pneumonitis (3 participants), rash (2 participants), an elevated aminotransferase/alanine aminotransferase level (1 participant), and a musculoskeletal event (1 participant). One participant with pretreatment KS herpesvirus (KSHV) viremia developed a polyclonal KSHV-associated B-cell lymphoproliferation and died. HIV was controlled in all participants. Increases in CD4 count were not statistically significant (median increase, 19 cells/µL; P = .18). Best tumor responses included complete response (lung, 1 patient), partial response (NHL, 2 patients), stable disease for 24 weeks or more (KS, 2 patients), stable disease for less than 24 weeks (15 patients), and progressive disease (8 patients); 2 patients were not evaluable. CONCLUSIONS AND RELEVANCE: Pembrolizumab has acceptable safety in patients with cancer, HIV treated with ART, and a CD4+ T-cell count of greater than 100 cells/µL but may be associated with KSHV-associated B-cell lymphoproliferation. Clinical benefit was noted in lung cancer, NHL, and KS. Anti-PD-1 therapy is appropriate for US Food and Drug Administration-approved indications and clinical trials in this population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02595866.
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Blastic plasmacytoid dendritic cell neoplasm is a very rare disease and in our case report we discuss the presentation of our patient, her treatment and response in addition for a discussion of the newly therapeutic options that are available.
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Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide), proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib), alkylating agents (bendamustine), AKT inhibitors (afuresertib), BTK inhibitors (ibrutinib), CDK inhibitors (dinaciclib), histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat), IL-6 inhibitors (siltuximab), kinesin spindle protein inhibitors (filanesib), monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984), and phosphoinositide 3-kinase (PI3K) inhibitors.
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Terapia Molecular Dirigida/métodos , Mieloma Múltiple/tratamiento farmacológico , Humanos , Terapia Molecular Dirigida/tendenciasRESUMEN
Half of a century ago, physicians managing chronic lymphocytic leukemia (CLL) recognized some of its presenting features such as lymphocytosis, lymphadenopathy, and splenomegaly. Subsequently, an enhanced understanding of the disease mechanisms involved in CLL led to new, more targeted treatments. There is now a plethora of treatments available for CLL. In this review article we discuss in detail several of the novel agents that are being studied or approved for the treatment of CLL including: phosphatidylinositol 3-kinase inhibitors (idelalisib and IPI-145), Bruton tyrosine kinase inhibitors (ibrutinib), B cell lymphoma 2 inhibitors (ABT-263 and ABT-199), new anti-CD20 monoclonal antibodies (obinutuzumab), cyclin-dependent kinase inhibitors (flavopiridol and dinaciclib), immunomodulators (lenalidomide) and chimeric antigen receptor T-cell therapy.