Current perspectives on the management of refractory or relapsed classic hodgkin lymphoma in brazil: Balancing efficacy, safety, and tolerability.

Classic Hodgkin lymphoma (CHL), which accounts for 90-95% of all cases of Hodgkin lymphoma, is the most frequent cancer in adolescents and the most frequent lymphoma in adolescents and young adults. Despite progressive improvements over past decades and the general sensitivity of CHL to frontline chemotherapy, approximately 10-15% of patients have refractory disease that either does not respond to such therapy or progresses after an initial partial response. In patients with refractory or relapsed disease, standard treatment until recently consisted mainly of salvage chemotherapy, in many cases followed by high-dose chemotherapy and autologous stem-cell transplantation. However, improved understanding of the pathobiology of CHL, coupled with the introduction of novel agents, has markedly changed the treatment landscape in the past decade. Although refractory or relapsed CHL continues to be challenging, the therapeutic landscape is undergoing profound changes brought about by novel agents, particularly brentuximab vedotin and immunotherapy. In this review, we discuss the most salient treatment options for adult patients with refractory or relapsed CHL, with a special focus on the Brazilian healthcare setting, which is constrained by inherent characteristics of this system. In the attempt to balance efficacy, safety and tolerability, practicing physicians must rely on clinical trials and on results from real-world studies, and use their own point of view and experience, as well as patient characteristics and previous therapy, to make treatment decisions for refractory or relapsed CHL.

Experiencia clínica de uso de Brentuximab-vedotin como terapia de linfoma de Hodgkin recaído o refractario en Hospital Guillermo Grant Benavente, Concepción, Chile / Clinical experience of using brentuximab-vedotin as therapy in relapsed/refractory Hodgkin's lymphoma at Hospital Guillermo Grant Benavente, Concepción, Chile

INTRODUCCIÓN: El linfoma de Hodgkin es una neoplasia de células B de buen pronóstico, pero con mala respuesta a quimioterapia en casos refractarios o recaídas. Brentuximab vedotin es un anticuerpo monoclonal antiCD30 aprobado para su uso en estos casos. El presente trabajo tiene como objetivo describir la experiencia clínica de los pacientes tratados con brentuximab vedotin bajo la modalidad de acceso expandido. MATERIAL Y MÉTODOS: Estudio retrospectivo sobre información clínica de pacientes diagnosticados de linfoma de Hodgkin refractario o en recaída y tratados con brentuximab-vedotin en el Hospital Regional de Concepción en el período 2015-2021. RESULTADOS: Se identificaron 7 pacientes, 5/7 de sexo masculino, con una mediana de edad de 35 años (21-50). Cinco casos fueron celularidad mixta y 2 esclerosis nodular. Cuatro estaban en etapa II, 1/7 en etapa III y 3/7 en etapa IV. La mediana de líneas de tratamiento previas fue 4 (3-5) y en 2 casos la recaída fue postrasplante. En 6/7 casos se empleó como inducción y en un caso se empleó como mantención postransplante autólogo de médula ósea. La administración fue ambulatoria por vía periférica con una mediana de dosis 150 mg y 10 ciclos. En un caso se necesitó ajuste de dosis por toxicidad. Tres de 6 pacientes lograron remisión completa y fueron a trasplante autólogo de médula ósea. CONCLUSIONES: brentuximab vedotin es un medicamento ambulatorio de baja toxicidad que puede optimizar el tratamiento de pacientes con linfoma de Hodgkin recaído-refractario.

INTRODUCTION: Hodgkin's lymphoma is a B-cell neoplasm with a good prognosis but a poor response to chemotherapy in refractory or relapsed cases. Brentuximab-vedotin is an anti-CD30 monoclonal antibody approved for use in these cases. This study aims to describe the clinical experience of patients treated with brentuximab-vedotin through expanded access modality. MATERIALS AND METHODS: A retrospective study on clinical information of patients diagnosed with refractory or relapsed Hodgkin's lymphoma treated with brentuximab-vedotin at the Regional Hospital of Concepción in the period 2015-2021. RESULTS: 7 patients were identified, 5/7 male, with a median age of 35 years (21-50). Five cases were mixed cellularity, and two were nodular sclerosis. Four were in stage II, 1/7 in stage III, and 3/7 in stage IV. The median number of previous treatment lines was 4 (3-5), and the relapse was post-transplantation in two cases. In 6/7 cases, brentuximab-vedotin was used as induction, and in one case, it was used as post-autologous bone marrow transplant maintenance. The administration was outpatient via a peripheral route with a median dose of 150 mg and ten cycles. In one case, dose adjustment was required due to toxicity. Three out of 6 patients achieved complete remission and underwent autologous stem cell transplantation. CONCLUSION: brentuximab-vedotin is an outpatient medication with low toxicity that can optimize the treatment of patients with relapsed-refractory Hodgkin's lymphoma.

Desensitization to Brentuximab Vedotin after anaphylaxis in refractory Hodgkin's lymphoma.

INTRODUCTION: Brentuximab vedotin (BV) is a monoclonal antibody that targets CD30 antigen. It is indicated for the treatment of CD30 + lymphomas and classical Hodgkin lymphoma (HL), including advanced (stage III-IV) untreated disease, relapsed/refractory disease, and consolidation after autologous hematopoietic stem cell transplantation. In clinical trials the incidence of a hypersensitivity reaction is 1.2%. CASES REPORT: We present 3 cases of patients with refractory HL and anaphylaxis to the administration of BV ( Table 1). Symptoms are analyzed using a grading system described by Brown (2004) and a desensitization protocol was performed with a total dose of 100 mg of BV in 4 solution bags with an initial concentration of 1:1000 of total dose for cases of severe anaphylaxis, and desensitization of 3 solution bags with baseline concentration of 1: 100 for cases of moderate anaphylaxis. MANAGEMENT & OUTCOME: Intradermal skin tests were positive. Before desensitization, premedication with methylprednisolone and chlorphenamine was administered, as well as fluid therapy with 0.9% physiological solution at 100 cc/hour at induction stage, 250 cc/hour at maintenance stage, and increased to 500 cc/hour in case of hypersensitivity reaction. DISCUSSION: Drug desensitization in 12 or 16 steps allows tolerable administration of brentuximab vedotin after moderate to severe anaphylaxis. The favorable response to treatment of these patients may indicate that desensitization is a viable strategy for patients with relapsed or refractory HL.

Mexican consensus on Hodgkin's lymphoma.

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.Hodgkin's lymphoma (HL) is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. HL is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

Mexican Consensus on Hodgkin's Lymphoma.

Hodgkin's lymphoma is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. Hodgkin's lymphoma is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.

Prognostic significance of CD30 expression in diffuse large B-cell lymphoma: A systematic review with meta-analysis.

BACKGROUND: CD30 is variably expressed in diffuse large B-cell lymphoma (DLBCL), but its prognostic potential for the affected patients remains debatable and unclear. Therefore, we aimed to determine the frequency of CD30 expression in DLBCL and its potential for prognostic determination. METHODS: An electronic systematic review was performed using multiple databases, followed by a quantitative meta-analysis to assess the frequency of CD30 expression with positivity cut-off values of >0% and >20%, and to determine its association with clinicopathological features and patients' survival. RESULTS: Using a cut-off value >0%, we observed that 3.5%-59.1% of the cases were considered positive for CD30. There was a significant association of the protein expression with a lower number of extra-nodal sites affected by the neoplasm, with Ann Arbor advanced stage, the absence of B-symptoms, the lack of MYC and BCL2 translocations, and a lower ECOG performance. Using a cut-off value >20%, we observed that 2.5%-36.7% of the cases were considered positive for CD30, being significantly associated with a lower number of extra-nodal sites affected by the neoplasm, Ann Arbor stages III/IV, non-GCB tumours, the lack of MYC and BCL2 translocations, and a lower ECOG value. CD30 expression was significantly associated with a better survival rate, regardless of what cut-off parameter was used. CONCLUSION: Despite variations in the cut-off values used to determine CD30 positivity in DLBCL, the expression of this protein seems to be associated with a higher survival rate and better prognosis.

Rapid desensitization to brentuximab vedotin after severe anaphylaxis in the treatment of refractory Hodgkin's lymphoma.

INTRODUCTION: Brentuximab vedotin is a monoclonal antibody drug conjugate used for the treatment of patients with Hodgkin lymphoma. Hypersensitivity reactions to brentuximab vedotin may include cutaneous, cardiovascular, respiratory, gastrointestinal and neurological signs and symptoms. CASE REPORT: We present the case of a 23-year-old Mexican female with stage IV progressive classical nodular sclerosing Hodgkin lymphoma who received multiple previous chemotherapy regimens. Brentuximab vedotin at 1.8 mg/kg (180 mg total dose), for 21-day cycles was indicated. Within 5 min of infusion of the 5th cycle of brentuximab, she developed severe anaphylaxis (hives, angioedema, diaphoresis, tachycardia, dyspnea, hypoxemia and loss of consciousness), which was successfully controlled with epinephrine, steroids and antihistamines.Management and outcome: Intradermal skin test at a concentration of 0.1 mg/ml was positive. Due to the severity of the symptoms and the lack of access to alternative treatments, we performed a desensitization protocol. A total of 180 mg of brentuximab was given in three bag solutions in 12 steps, with an initial concentration dose of 1/100 of the total dose in a course of 5.56 h with no hypersensitivity reactions. DISCUSSION: Severe anaphylaxis has been reported in 1.2% of patients receiving brentuximab vedotin. Patients who are treated by rapid drug desensitization with their first option therapy present a favorable survival rate with better cost-effectiveness in comparison to second-line treatment.

Consenso mexicano de linfoma de Hodgkin / Mexican Consensus on Hodgkin's Lymphoma

Resumen El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.

Abstract Hodgkin's lymphoma is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. Hodgkin's lymphoma is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

Antibody-drug conjugates: the new generation of biotechnological therapies against cancer.

Therapeutic antibodies are recombinant proteins used in the treatment of cancer. There is a new generation of monoclonal antibodies with activity against cancer cells, known as antibody-drug conjugates. These molecules are made up of three elements: a monoclonal antibody, a highly potent cytotoxic drug, and a chemical linker that binds them together. The antibody recognizes tumor antigens, thereby allowing targeted delivery of the cytotoxic agent to cancer cells. After recognizing its antigen, the antibody-drug conjugate is endocytosed by the target cells, where the protein fraction is degraded into lysosomes, releasing the cytotoxic drug. This article reviews antibody-drug conjugates general characteristics and describes the clinical evidence of efficacy and safety of the first four approved by regulatory agencies in the United States and Europe.

Los anticuerpos terapéuticos son proteínas recombinantes empleadas en el tratamiento del cáncer. Existe una nueva ­generación de anticuerpos monoclonales con actividad contra las células cancerosas, conocidos como anticuerpos conjugados a fármacos. Estas moléculas están integradas por tres elementos: un anticuerpo monoclonal, un fármaco citotóxico con alta potencia y un enlazador químico que los une. El anticuerpo reconoce antígenos tumorales, por lo que permite la entrega dirigida del agente citotóxico hacia las células cancerosas. Tras el reconocimiento de su antígeno, el anticuerpo conjugado a fármaco es endocitado por las células blanco, donde se induce la degradación lisosomal de la fracción proteica y se libera el fármaco citotóxico. En el presente artículo se revisan las características generales de los anticuerpos conjugados a fármacos y se describe la evidencia clínica de la eficacia y seguridad de los primeros cuatro aprobados por las agencias reguladoras de Estados Unidos y Europa.

Anticuerpos conjugados a fármaco: la nueva generación de terapias biotecnológicas contra el cáncer / Antibody-drug conjugates: the new generation of biotechnological therapies against cancer

Resumen Los anticuerpos terapéuticos son proteínas recombinantes empleadas en el tratamiento del cáncer. Existe una nueva generación de anticuerpos monoclonales con actividad contra las células cancerosas, conocidos como anticuerpos conjugados a fármacos. Estas moléculas están integradas por tres elementos: un anticuerpo monoclonal, un fármaco citotóxico con alta potencia y un enlazador químico que los une. El anticuerpo reconoce antígenos tumorales, por lo que permite la entrega dirigida del agente citotóxico hacia las células cancerosas. Tras el reconocimiento de su antígeno, el anticuerpo conjugado a fármaco es endocitado por las células blanco, donde se induce la degradación lisosomal de la fracción proteica y se libera el fármaco citotóxico. En el presente artículo se revisan las características generales de los anticuerpos conjugados a fármacos y se describe la evidencia clínica de la eficacia y seguridad de los primeros cuatro aprobados por las agencias reguladoras de Estados Unidos y Europa.

Abstract Therapeutic antibodies are recombinant proteins used in the treatment of cancer. There is a new generation of monoclonal antibodies with activity against cancer cells, known as antibody-drug conjugates. These molecules are made up of three elements: a monoclonal antibody, a highly potent cytotoxic drug, and a chemical linker that binds them together. The antibody recognizes tumor antigens, thereby allowing targeted delivery of the cytotoxic agent to cancer cells. After recognizing its antigen, the antibody-drug conjugate is endocytosed by the target cells, where the protein fraction is degradated into lysosomes, releasing the cytotoxic drug. This article reviews antibody-drug conjugates general characteristics and describes the clinical evidence of efficacy and safety of the first four approved by regulatory agencies in the United States and Europe.

Dermal xanthomatous infiltrates after brentuximab vedotin therapy in mycosis fungoides with large-cell transformation: A novel histologic finding.

Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas. Large-cell transformation of MF has been associated with disease progression and overall poor outcome. The expression of CD30, which defines anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis, might also occur in a subset of patients with MF, with or without large-cell transformation. Brentuximab vedotin is an anti-CD30 monoclonal antibody which has been proven to be a safe and effective therapeutic agent in the treatment of CD30-positive lymphomas, such as Hodgkin lymphoma and ALCL. Recently, brentuximab vedotin has been shown to have a significant clinical activity in treatment-refractory or advanced MF or Sezary syndrome with a wide-range of CD30 expression levels. We report a patient with MF tumor stage with large-cell transformation and low CD30 expression with good response to brentuximab vedotin and unusual extensive xanthomatous changes in the follow-up biopsy.