Alejandro Martín García-Sancho

• MD, PhD
• Medical Doctor at Hospital Universitario de Salamanca

Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous disease characterized by a limited number of molecularly defined subtypes. Recently, genomic-based algorithms have been proposed for the classification of this disease. The whole exome sequencing was conducted on 108 diagnostic samples of diffuse large B-cell lymphoma (DLBCL). Somatic variant...

Background Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide and is characterized by its heterogeneity. Although first-line therapy improves survival outcomes for DLBCL patients, approximately one third will relapse, often with a poor prognosis. Among the factors influencing prognosis and response to...

The peripheral blood lymphocyte‐to‐monocyte ratio (LMR) has been shown to predict outcomes in follicular lymphoma (FL). Among 1018 patients from the RELEVANCE trial (for previously untreated, high tumour burden FL), the median LMR was 2.5 (range, 0.3–93.5) and an LMR cut‐off of 2 was mostly associated with survival end‐points. Patients with an LMR...

Background: Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for high-dose chemotherapy have limited treatment options and poor life expectancy. The purpose of this study is to identify a serum metabolomic profile that may be predictive of outcome in patients with R/R-DLBCL. Methods: This study inc...

Background: Assessment of bone marrow infiltration (BMI) is part of the initial staging of mantle cell lymphoma (MCL), although BMI evaluated by biopsy (BMB) is not considered significant in the MIPI scales, and standardized recommendations remain lacking. Objectives: To evaluate the accuracy and prognostic impact of BMI assessed by PET/CT and BMB...

INTRODUCTION: Consolidation with ASCT after induction immunochemotherapy (ICT) is the standard strategy in MCL to prolong progression-free survival (PFS) in young fit eligible patients since 2005. HiDAC-based ICT further improved these results and, years later, Rituximab Maintenance (RM) prolongued PFS and overall survival (OS) not only in young pa...

Introduction: Patients with relapsed or refractory (R/R) DLBCL have a poor prognosis, even if treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). CAR T therapy provides long-term remission in only 40% of patients, and some cannot receive CAR T therapy due to fitness, geographic, or financial limitations. Epcoritamab i...

Background: Liso-cel is an autologous, CD19-directed, 4-1BB CAR T cell product that was recently approved by the United States Food and Drug Administration for the treatment of patients with 3L+ R/R FL based on results from the TRANSCEND FL study (NCT04245839). Other CAR T cell therapies approved for 3L+ R/R FL include axi-cel and tisa-cel. Because...

INTRODUCTION: MCL remains incurable and its management widely heterogeneous in clinical practice. We analyzed how the patterns and sequencing of treatments have evolved in Spain over the years and their impact on the survival of patients with MCL. PATIENTS AND METHODS: We retrospectively analyzed the management, efficacy data and progression-free a...

Introduction Large B cell lymphoma (LBCL) presents as limited stage (LS) in 25-30% of patients. This subgroup has been defined as I-II Ann Arbor (AA) stage with non-bulky disease (commonly <10 cm). Prognosis is favorable with overall survival (OS) at 10 years at least of 70-80%. The IPI has limited utility as most patients by definition have a favo...

Introduction: Bispecific antibodies (BsAbs) are approved for patients with relapsed/refractory (R/R) follicular lymphoma (FL) based on single-arm clinical trials. These T-cell engaging agents achieve approximately 60% complete response rate (CRR), but information regarding real-world prognostic factors is scarce. In light of the deleterious impact...

Introduction. The gut microbiota is crucial for the development and function of the immune system and is considered a significant factor in the efficacy of immunotherapies, including CAR-T cells. However, the mechanisms of this influence remain unclear. Short Chain Fatty Acids (SCFAs), metabolites produced through microbial fermentation, play a rol...

Introduction Salvage treatment for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) is challenging. High-dose therapy and autologous stem cell transplantation (ASCT) was the choice for eligible pts. For those not candidates there was not a standard second-line (2L) and the available options were not considered curative alt...

Introduction PMBL accounts for 2-4% of non Hodgkin lymphomas (NHL), predominantly affects young women and presents with a bulky mediastinal mass, often with pleural and pericardial effusions. There is no consensus on upfront treatment for PMBL, although some retrospective studies suggest that more intensive regimens than R-CHOP-21 could improve eff...

Introduction: The advent of T-cell engaging strategies for relapsed/refractory (r/r) non-Hodgkin lymphoma patients has completely changed the prognosis of this patient population. Bispecific antibodies (BsAbs) have shown impressive response rates and a favourable toxicity profile in the pivotal clinical trials, but real-world data to illustrate out...

Background: In the primary analysis of TRANSCEND FL (NCT04245839), a global, phase 2 study, liso-cel showed an ORR of 97%, CR rate of 94%, and favorable safety in pts with second-line (2L) or later R/R FL. Here, we report results in pts with third-line or later (3L+) and 2L FL with high-risk disease features after approximately 2 y of follow-up. Me...

Background: Mogamulizumab (moga) targets the CC chemokine receptor 4 (CCR4), widely expressed on malignant T cells in patients (pts) with cutaneous T-cell lymphoma (CTCL). Moga depletes tumor cells in CTCL and is approved for relapsed/refractory mycosis fungoides (MF)/Sézary syndrome (SS) after ≥1 systemic therapy. The licensed dosing schedule cons...

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a standard approach for patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) after Bruton tyrosine kinase inhibitor (BTKi) failure. Patient selection and management throughout the CAR-T process is challenging in the MCL setting, with a high dropout rate and increased r...

Introduction: Brexu-cel is an autologous anti-CD19 CAR T-cell therapy approved for adults with R/R MCL in the US and EU (after ≥2 prior lines of therapy [LoT], including a BTKi in EU), based on results from Cohort 1 of ZUMA-2 (NCT02601313). Brexu-cel demonstrated an objective response rate (ORR) of 91%, a complete response (CR) rate of 68%, and a m...

Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients...

Testicular large B‐cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune‐privileged site and has recently been recognized as a distinct entity from diffuse large B‐cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B‐cell lymphomas of...

The impact of phenotypic, clonal, and functional heterogeneity of chimeric antigen receptor (CAR)-T cells on clinical outcome remains understudied. Here, we integrate clonal kinetics with transcriptomic heterogeneity resolved by single-cell omics to interrogate cellular dynamics of non-transduced (CARneg) and transduced (CARpos) T cells, in the inf...

A phase 2, international, open-label, non-randomized, single-arm trial was conducted to evaluate the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, as monotherapy for relapsed/refractory peripheral T-cell lymphoma (PTCL) and to evaluate tumor mutation profile as a biomarker of response. Adults with relapsed/refractory PTCL rece...

Purpose Natural killer (NK) cells are traditionally identified by flow cytometry using a combination of markers (CD16/CD56/CD3), because a specific NK-cell marker is still missing. Here we investigated the utility of CD314, CD335 and NKp80, compared to CD16/CD56/CD3, for more robust identification of NK-cells in human blood, for diagnostic purposes...

Simple Summary At least 40% of treated patients with large B-cell lymphoma do not respond to first-line treatment or experience disease recurrence, and less than 50% of patients respond to second-line salvage immunochemotherapy and can proceed to the historical standard of care of autologous stem-cell transplantation (ASCT). This study aimed to ass...

Purpose: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and methods: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL wit...

This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and person...

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor out...

7068 Background: TRANSCEND FL primary analysis (NCT04245839) demonstrated very high response rates and manageable safety with liso-cel in second-line or later (2L+) FL, including 2L high-risk FL. Here, we report outcomes in subgroups of pts by BT status. Methods: TRANSCEND FL, a global, phase 2, single-arm, open-label study, evaluated liso-cel in a...

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next‐generation sequencing (NGS) approach (EuroClonality‐NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R‐CHOP‐treated diffuse large B‐cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cyc...

Over 60% of relapsed/refractory (R/R) large B‐cell lymphoma (LBCL) patients who receive chimeric antigen receptor (CAR) T cells will experience disease progression. There is no standard next line of therapy and information in this setting is scarce and heterogeneous. We analyzed 387 R/R LBCL patients who progressed after CAR T cells from July 2018...

Background Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predict...

Background: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in cl...

How phenotypic, clonal, and functional heterogeneity of the CAR-T-cells impact clinical outcomes remain understudied. Here, we integrated clonal kinetics with transcriptomic heterogeneity resolved by single-cell omics to explore cellular dynamics response of both non-transduced (CARneg) and transduced (CARpos)T-cells. CARneg and CARposT-cells were...

Overall, around 40% of patients with diffuse large B-cell lymphoma (DLBCL) have refractory disease or relapse after the first line of treatment. Until relatively recently, the prognosis of patients with relapsed or refractory DLBCL was very poor and treatment options were very limited. In recent years, several novel therapies have been approved tha...

Background and objective: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the...

Background: Up to one-third of patients (pts) with 1L LBCL treated with R-CHOP do not achieve long-term remission or cure depending on disease stage. Outcome prediction beyond the International Prognostic Index (IPI) score is difficult due to the lack of reproducibility of common biomarkers. ctDNA offers potential as a sensitive biomarker to identi...

Background: Results with CD19-directed CAR T cell therapy in patients (pts) with second-line (2L) R/R follicular lymphoma (FL) and high-risk features, such as progression of disease within 24 months (POD24) from diagnosis or double refractory to anti-CD20 antibody plus alkylator, have not been previously reported. TRANSCEND FL (NCT04245839), a glob...

Introduction: Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. There is no standard treatment after CAR T-cell therapy progression and a wide range of outcomes are observed in this patient population. Beside...

Introduction Up to 40% of pts with diffuse large B-cell lymphoma (DLBCL) relapse after first-line chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). CELMoD agents such as GOLCA potently degrade target proteins Ikaros/Aiolos, resulting in antiproliferative, apoptotic, and immunomodulatory activit...

In everyday clinical practice, the therapeutic pathway of autologous CAR T-cell starts from leukapheresis, but the drug is infused on average 4-7 weeks later. Between leukapheresis and CAR T infusion patients may die following disease progression or exit the therapeutic pathway due to comorbidities or other reasons, thereby introducing a potential...

Introduction. Autologous chimeric antigen receptor (CAR) T-cell therapy targeting CD19 is an effective treatment for relapsed or refractory large B-cell lymphoma (LBCL). Real-world studies have reported improved outcomes in terms of safety and efficacy in comparison with pivotal trials. These differences have been associated to a learning curve in...

Background: Median age at diagnosis of diffuse large B cell lymphoma (DLBCL) patients is 66 years; 40% of patients are diagnosed at an age greater than 70 years. CAR-T cell therapy is approved for the treatment of relapsed/refractory DLBCL patients; however, a deeper understanding of outcomes in patients older than 70 years is needed. Our aim was t...

Introduction: High dose therapy and Autologous Stem Cell Transplantation (ASCT) has remained the treatment of choice for transplant-eligible patients with relapsed/refractory (R/R) large B cell lymphoma (LBCL) and chemosensitive disease. Recently, CART therapy has been approved in second line for patients with primary refractory disease or early re...

Background: In TRANSCEND FL (NCT04245839), a global, phase 2, open-label, single-arm, multicohort, pivotal study, the CAR T cell therapy liso-cel showed promising efficacy and safety in pts with R/R FL (Morschhauser F, et al. Hematol Oncol 2023;41[S2]:877-880). Here, we present corresponding data for PROs. Methods: Adults with R/R FL after ≥ 1 prio...

Background: Diffuse Large B Cell Lymphomas are still a significantly heterogeneous disease with few molecularly defined entities. Recently genomic based algorithms have been proposed for DBCL NOS disease classification, including the Lymphgen tool 1. Other large B cell lymphoma entities, including High Grade BCL Dual Hit or plasmablastic lymphoma r...

Introduction: Several new therapeutic agents have been approved in recent years for the treatment of relapsed/refractory (R/R) Large B cell lymphoma (LBCL) (diffuse large B cell lymphoma [DLBCL] and high-grade B cell lymphomas [HGBCL]), such as new monoclonal antibodies (MA), bispecific antibodies (BA) and CAR-T cell therapy. The objective of our s...

TITLE Early identification of very high risk patients with Diffuse Large B Cell Lymphoma (DLBCL) by PET-CT. INTRODUCTION Early identification of high risk DLBCL after the start of treatment continues to be a challenge that has not been fully resolved. The main aim of this study was to analyze the prognostic impact on progression free survival (PFS)...

Background and Significance CD20×CD3 bispecific antibodies (bsAbs) have emerged as an important immunotherapeutic approach for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). These agents have shown compelling efficacy in indolent B-NHL, with the CD20×CD3 bsAb odronextamab demonstrating 75% complete response (CR) rates and encouragin...

Introduction ARID1A mutation (ARID1Amut) has a high incidence in OCCC (up to 60%) and EC (up to 40%), with evidence as a negative prognostic marker for treatment resistance and outcomes. EZH2 inhibition in ARID1Amut solid tumors results in tumor growth inhibition (Bitler et al. Nat Med 2015;21:231–238). Preliminary Phase II (NCT04104776) efficacy,...

The phase 3 SELENE study evaluated ibrutinib + chemoimmunotherapy (CIT; bendamustine and rituximab [BR] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Adult patients who had received ≥ 1 prior line of CIT were ran...

Background: In the pre-chimeric antigen receptor (CAR)-T cell therapy era, the SCHOLAR-1 study identified a group of patients with refractory aggressive B-cell lymphoma (ABCL) with particularly poor prognoses. We recently published our real-world data from Spain, focused on this SHOLAR-1 refractory group, and compared patients who underwent CAR-T...

Background and objective: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the...

[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].

Purpose: The combination of zanubrutinib plus obinutuzumab was found to be well tolerated with an early signal of efficacy in a phase 1b study. ROSEWOOD is a phase II, randomized study that assessed the efficacy and safety of zanubrutinib plus obinutuzumab versus obinutuzumab in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Me...

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CD...

Diffuse large B‐cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and efficacy of adding lenalidomide to R‐ESHAP (LR‐ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1–14 of every 2...

Nodal peripheral T‐cell lymphoma (PTCL) with a T follicular helper phenotype (PTCL‐TFH) is a new type of PTCL. We aimed to define its clinical characteristics and prognosis compared to PTCL not otherwise specified (PTCL‐NOS) and angioimmunoblastic T‐cell lymphoma (AITL). This retrospective observational study included 175 patients diagnosed with PT...

Background CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. Method Eleven FL patients treate...