Role of Bispecific Antibodies in Relapsed/Refractory Diffuse Large B-Cell Lymphoma in the CART Era

Diffuse large B-cell lymphoma is an aggressive and biologically heterogeneous disease. R-CHOP is the standard first line therapy and cures more than 60% of patients. Salvage high-dose chemotherapy with autologous stem cell transplant remains the standard second-line treatment for relapsed or refractory patients, and recently, three CD19 chimeric antigen receptor T cells (CART) cell products have been approved beyond 2 prior lines of systemic therapy. Nevertheless, some patients are not eligible for transplant or CARTs, or progress after these treatments. In this context, IgG-like bispecific antibodies (BsAbs) have been designed to treat B-cell lymphomas. They combine two different monospecific antigen-binding regions that target CD20 on B cells and engage T cells via CD3 in a 1:1 or 2:1 CD20:CD3 antigen binding fragment (Fab) format. The results of different phase 1 trials with BsAbs, including mosunetuzumab, glofitamab, epcoritamab and odeonextamab, have been recently published. They are infused intravenously or subcutaneously, and have a favorable toxicity profile, with reduced cytokine release syndrome and neurological toxicity. Moreover, these BsAbs have demonstrated very promising efficacy in B-cell lymphomas, including in aggressive lymphomas. New trials are currently ongoing to confirm BsAbs efficacy and tolerability, as well as to explore its efficacy in different lines of therapy or in combination with other drugs

Bacteremia caused by CDC group IV c-2 in a patient with acute leukemia.

Human infection due to CDC group IV c-2, a gram negative bacillous, are rare. We describe a case of nosocomial bacteremia caused by this organism in a neutropenic patient with acute lymphoblastic leukemia and include a literature review of CDC group IV c-2 infection in patients with hematologic malignancies

Combined treatment with anti-CD20 (rituximab) and CHOP in relapsed advanced-stage follicular lymphomas

We studied the safety and efficacy of combined treatment with rituximab plus CHOP in 16 patients with relapsed advanced-stage follicular lymphomas. The intent-to-treat overall response rate (ORR) was 88%, 75% complete remissions (CR) and 13% partial remissions (PR). At a median follow-up of 18 months, 63% of the patients are alive (50% CR). The combination of rituximab and CHOP in relapsed advanced-stage follicular lymphomas achieves high ORRs and CRs, with low toxicity except for in previously autografted patients

Clinical characteristics and risk of relapse for patients with stage I-II diffuse large B cell lymphoma treated in first line with immunochemotherapy

Diffuse large b-cell lymphoma (DLBCL) is an aggressive and potentially curable lymphoma that presents itself as stage I-II in 30% of all cases. It is known that in these localized stages, 15-20% of patients treated without rituximab eventually relapse, but less data exist regarding rituximab era. We have analyzed clinico-pathological features and risk of relapse in 98 patients with I-II stage DLBCL in complete response (CR) or unconfirmed CR (CRu) after first-line treatment consisting of immunochemotherapy. Twelve patients (12.2%) eventually relapsed. Late relapse, more than two years after diagnosis, occurred in three patients, and early relapse, less than two years after diagnosis, was documented in nine patients. Median time from diagnosis to relapse was 0.61 years for patients with early relapse and 3.66 years for patients with late relapse. The second CR rate obtained was similar in the late and in early relapsing patients, being 33% versus 44% (p = 0.072), respectively. Three-year overall survival (OS) was 22% for early relapsing patients and 33% for late relapsing patients (p = 0.65). In conclusion, patients who are diagnosed with stage I-II DLBCL and achieve a CR/CRu with first line immunochemotherapy have a good prognosis. However, a proportion of patients relapse, and this is less frequent in patients treated with first line with immunochemotherapy. These patients have a poor prognosis

Serum-free culture conditions for the generation of dendritic cells from cord blood CD34+ hematopoietic progenitors: phenotypic and functional analysis

Increasing pre-clinical and clinical data suggest the efficiency of dendritic cells (DCs) in cancer immunotherapy. Relapse after cord blood hematopoietic progenitors (CBHP) transplantation is an unresolved problem. DCs obtained from CBHP could be an interesting tool for relapse treatments, but the low number of CBHP hinder their use for DC generation

Tratamiento con interleukina 2 en pacientes con neoplasia linfoide en remisión completa con alto riesgo de recaida

Descripciò del recurs: 8 setembre 2011INTRODUCCIÓN El 50% de los pacientes con neoplasias linfoides no se curan tras tratamiento estándar con quimioterapia y/o radioterapia, lo que hace imprescindible ensayar nuevos fármacos con diferentes mecanismos de acción. La interleukina 2 (IL2) es una citoquina fundamental en la repuesta inmune normal del individuo, que, in vitro, activa a las células NK ("natural killer" o asesinas naturales) produciendo un efecto antitumoral. En ensayos clínicos fase I-II con IL2 a dosis altas endovenosa se han observado respuestas en varios tipos de tumores, entre ellos las neoplasias linfoides. OBJETIVOS Valorar la tolerancia, los cambios inmunes in vivo y la eficacia de dosis bajas de IL2 subcutánea (sc) como tratamiento de mantenimiento en pacientes con neoplasias linfoides en remisión completa con alto riesgo de recaída PACIENTES Y METODOS El ensayo fue aprobado por el Comité Ético del Institut Catalá d'Oncologia. Se incluyeron pacientes diagnosticados de leucemia linfoblástica aguda (LLA), linfomas no-Hodgkin (LNH) y linfomas de Hodgkin (LH) en segunda remisión o posterior o en primera remisión con factores de mal pronóstico. El tratamiento consistió en IL2 4,5 x106 UI / día sc de lunes a viernes durante 12 semanas de forma ambulatoria. Se realizaron estudios de subpoblaciones linfocitarias en sangre periférica mediante inmunofenotipo, actividad citotóxica ex vivo mediante la técnica de liberación en 4 horas de cromo y niveles de diferentes citoquinas mediante enzimoinmunoensayo. Los resultados se compararon con los de 43 donantes sanos. Se realizó un estudio de casos y controles para evaluar diferencias en la supervivencia libre de enfermedad (SLE). RESULTADOS Se incluyeron 15 pacientes: 3 LLA, 7 LNH, 5 LH, con una mediana de edad de 39 años (límites 15-63). Un paciente no completo el tratamiento por progresión. La dosis se redujo en 4 pacientes por toxicidad, en 3 de ellos por astenia grado 3. El tratamiento indujo los siguientes cambios in vivo: eosinofilia (p=0,009), proliferación de células NK de 11% a 35% de los linfocitos (p=0,0006), y aumento de la actividad citotóxica tipo LAKe (células asesinas efectoras activadas por linfoquinas) de 6x10-3 UL/ml a 80x 10-3 UL/ml (p=0,02). Estos efectos alcanzaron el pico máximo a las 4 semanas de tratamiento y se mantuvieron estables durante el mismo. El aumento de células NK se correlacionó con el aumento de la actividad LAKe (r=0,96, p 0,0001). En un estudio de casos y controles compararon los 15 casos (mediana de SLE: 11,1 meses) con 22 controles históricos (mediana de SLE: 9,7 meses) y no se observaron diferencias significativas (p=0.9). CONCLUSIONES El tratamiento con IL2 sc a dosis bajas durante 12 semanas estimula la proliferación de células NK, lo que genera actividad citotóxica in vivo, en pacientes con neoplasias linfoides. En nuestro estudio, la demostración de diferencias significativas en la supervivencia es difícil dado el escaso número de pacientes tratados. Sin embargo, la intensa inmunomodulación que se alcanza, así como la poca toxicidad asociada, constituyen un primer paso para continuar explorando la inmunoterapia en pacientes con neoplasias linfoide

Low-Dose PET/CT and Full-Dose Contrast-Enhanced CT at the Initial Staging of Localized Diffuse Large B-Cell Lymphomas

Computed tomography (CT) has been used as the reference imaging technique for the initial staging of diffuse large B-cell lymphoma until recent days, when the introduction of positron emission tomography (PET)/CT imaging as a hybrid technique has become of routine use. However, the performance of both examinations is still common. The aim of this work was to compare the findings between low-dose 2-deoxy-2-(F-18) fluoro-D-glucose (F-18-FDG) PET/CT and full-dose contrast-enhanced CT (ceCT) in 28 patients with localized diffuse large B-cell lymphoma according to PET/CT findings, in order to avoid the performance of ceCT. For each technique, a comparison in the number of nodal and extranodal involved regions was performed. PET/CT showed more lesions than ceCT in both nodal (41 vs. 36) and extranodal localizations (16 vs. 15). Disease staging according to both techniques was concordant in 22 patients (79%) and discordant in 6 patients (21%), changing treatment management in 3 patients (11%). PET/CT determined a better staging and therapeutic approach, making the performance of an additional ceCT unnecessary

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma

Tafasitamab; B-cell lymphomaTafasitamab; Linfoma de células BTafasitamab; Limfoma de cèl·lules BTafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months’ follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months’ follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085

Spanish Lymphoma Group (GELTAMO) guidelines for the diagnosis, staging, treatment, and follow-up of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% of non-Hodgkin lymphoma (NHL) cases in adult series. DLBCL is characterized by marked clinical and biological heterogeneity, encompassing up to 16 distinct clinicopathological entities. While current treatments are effective in 60% to 70% of patients, those who are resistant to treatment continue to die from this disease. An expert panel performed a systematic review of all data on the diagnosis, prognosis, and treatment of DLBCL published in PubMed, EMBASE and MEDLINE up to December 2017. Recommendations were classified in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework, and the proposed recommendations incorporated into practical algorithms. Initial discussions between experts began in March 2016, and a final consensus was reached in November 2017. The final document was reviewed by all authors in February 2018 and by the Scientific Committee of the Spanish Lymphoma Group GELTAMO

The direct and indirect effects of COVID‐19 pandemic in a real‐life hematological setting

Background: Clinical outcomes of novel coronavirus 2019 disease (COVID-19) in onco-hematological patients are unknown. When compared to non-immunocompromised patients, onco-hematological patients seem to have higher mortality rates. Aims: We describe the characteristics and outcomes of a consecutive cohort of 24 onco-hematological patients with COVID-19 during the first month of the pandemic. We also describe variations in healthcare resource utilization within our hematology department. Methods and results: Data from patients between the first month of the pandemic were retrospectively collected. Clinical and logistic data were also collected and compared with the average values from the prior 3 months of activity. Prevalence of COVID-19 in our hematological population was 0.4%. Baseline characteristics were as follows: male sex: 83%, lymphoid diseases: 46%, median age: 69 (22-82) years. Median follow-up in survivors was 14 (9-28) days and inpatient mortality rate was 46%. Average time to moderate/severe respiratory insufficiency and death were 3 (1-10) and 10 (3-18) days, respectively. Only 1 out of every 12 patients who developed moderate to severe respiratory insufficiency recovered. Upon univariate analysis, the following factors were associated with higher mortality: age ≥ 70 years (P = .01) and D-dimer ≥900 mcg/L (P = .04). With respect to indirect effects during the COVID-19 pandemic, and when compared with the prior 3 months of activity, inpatient mortality (excluding patients with COVID-19 included in the study) increased by 56%. This was associated with a more frequent use of vasoactive drugs (+300%) and advanced respiratory support (+133%) in the hematology ward. In the outpatient setting, there was a reduction in initial visits (-55%) and chemotherapy sessions (-19%). A significant increase in phone visits was reported (+581%). Conclusion: COVID-19 pandemic is associated with elevated mortality in hematological patients. Negative indirect effects are also evident within this setting