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Autologous chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of lymphoid malignancies, leading to the approval of CD19-CAR T cells for B-cell lymphomas and acute leukaemia, and more recently, B-cell maturation antigen-CAR T cells for multiple myeloma. The long-term follow-up of patients treated in the early clinical trials demonstrates the possibility for long-term remission, suggesting a cure. This is associated with a low incidence of significant long-term side effects and a rapid improvement in the quality of life for responders. In contrast, other types of immunotherapies require prolonged treatments or carry the risk of long-term side effects impairing the quality of life. Despite impressive results, some patients still experience treatment failure or ultimately relapse, underscoring the imperative to improve CAR T-cell therapies and gain a better understanding of their determinants of efficacy to maximize positive outcomes. While the next-generation of CAR T cells will undoubtingly be more potent, there are already opportunities for optimization when utilizing the currently available CAR T cells. This review article aims to summarize the current evidence from clinical, translational and fundamental research, providing clinicians with insights to enhance their understanding and use of CAR T cells.
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There are limited data assessing the risk scores for primary treatment failure (PTF) classical Hodgkin lymphoma (cHL, PTF-cHL) undergoing autologous hematopoietic cell transplantation (auto-HCT). ECLIPSE is a multicenter retrospective cohort of patients with PTF- cHL (15 years or older) diagnosed on or after Jan 1, 2005, at 15 US medical centers. PTF was defined as one of the following patterns of failure: [1] progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression [PP]); [2] partial response (PR) or stable disease (SD) by imaging after completion of frontline treatment (PR/SD); [3] progression of disease by imaging (and confirmed by biopsy) within 12 months of frontline therapy completion after prior documentation of complete response (CR, early relapse [ER]). A total of 478 patients were included in the analysis. Among these, 217 (45%) were PP, 86 (18%) were PR/SD, and 175 (37%) were ER. The 6-month and 1-year cumulative incidence of non-relapse mortality following auto-HCT was 0.9% and 1.1%, respectively. The median PFS and OS following auto-HCT were 4.33 years and 10.09 years, respectively. While those not in CR at the time of auto-HCT was associated with inferior PFS and OS, advanced age and those diagnosed before 2011 were associated with inferior OS. This study showcases the safety and long-term efficacy of auto-HCT, even in patients with high risk disease who are traditionally considered chemo-refractory and will serve as a benchmark for the ongoing transplant vs no transplant trials.
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ABSTRACT: Although initial therapy of mantle cell lymphoma (MCL) is not standardized, bendamustine plus rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance after induction is often used. Thus, the open-label, randomized phase 2 ECOG-ACRIN Cancer Research Group E1411 trial was designed to test 2 questions: (1) does addition of bortezomib to BR induction (BVR) and/or (2) addition of lenalidomide to rituximab (LR) maintenance improve progression-free survival (PFS) in patients with treatment-naïve MCL? From 2012 to 2016, 373 previously untreated patients, 87% aged ≥60 years, were enrolled in this trial. At a median follow-up of 7.5 years, there is no difference in the median PFS of BR compared with BVR (5.5 vs 6.4 years; hazard ratio [HR], 0.90; 90% confidence interval [CI], 0.70-1.16). There were no unexpected additional toxicities with BVR treatment compared with BR, with no impact on total dose/duration of treatment received. Independent of the induction treatment, addition of lenalidomide did not significantly improve PFS, with median PFS in R vs LR (5.9 vs 7.2 years; HR, 0.84; 90% CI, 0.62-1.15). Most patients completed the planned 24 cycles of LR at the scheduled dose. In summary, adding bortezomib to BR induction does not prolong PFS in treatment-naïve MCL, and LR maintenance was not associated with longer PFS compared with R alone after BR. Nonetheless, the >5-year median PFS outcomes in this prospective cooperative group trial indicate the efficacy of BR followed by R maintenance as highly effective initial therapy for older patients with MCL. This trial was registered at www.clinicaltrials.gov as #NCT01415752.
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Protocolos de Quimioterapia Combinada Antineoplásica , Clorhidrato de Bendamustina , Bortezomib , Lenalidomida , Linfoma de Células del Manto , Quimioterapia de Mantención , Rituximab , Humanos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/uso terapéutico , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Lenalidomida/administración & dosificación , Lenalidomida/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano de 80 o más Años , Adulto , Quimioterapia de Inducción , Supervivencia sin ProgresiónRESUMEN
Antibody-drug conjugates (ADCs) represent one of the most successful therapeutic approaches introduced in clinical practice in the last few years. Loncastuximab tesirine (ADCT-402) is a CD19 targeting ADC, in which the antibody is conjugated through a protease cleavable dipeptide linker to a pyrrolobenzodiazepine (PBD) dimer warhead (SG3199). Based on the results of a phase 2 study, loncastuximab tesirine was recently approved for adult patients with relapsed/refractory large B-cell lymphoma. We assessed the activity of loncastuximab tesirine using in vitro and in vivo models of lymphomas, correlated its activity with CD19 expression levels, and identified combination partners providing synergy with loncastuximab tesirine. Loncastuximab tesirine was tested across 60 lymphoma cell lines. Loncastuximab tesirine had strong cytotoxic activity in B-cell lymphoma cell lines. The in vitro activity was correlated with CD19 expression level and intrinsic sensitivity of cell lines to the ADC's warhead. Loncastuximab tesirine was more potent than other anti-CD19 ADCs (coltuximab ravtansine, huB4-DGN462), albeit the pattern of activity across cell lines was correlated. Loncastuximab tesirine activity was also largely correlated with cell line sensitivity to R-CHOP. Combinatorial in vitro and in vivo experiments identified the benefit of adding loncastuximab tesirine to other agents, especially BCL2 and PI3K inhibitors. Our data support the further development of loncastuximab tesirine as a single agent and in combination for patients affected by mature B-cell neoplasms. The results also highlight the importance of CD19 expression and the existence of lymphoma populations characterized by resistance to multiple therapies.
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All chimeric antigen receptor (CAR) T-cell products currently approved by the FDA are autologous, which poses several challenges for widespread use. In this issue, Degagné and colleagues present their preclinical research on creating off-the-shelf CAR T cells for multiple myeloma. They utilized the CRISPR/Cas12a genome editing platform and gene knock-in techniques to eliminate alloreactivity and decrease susceptibility to natural killer (NK)-cell elimination. This work has led to an ongoing phase I trial of off-the-shelf CAR T cells for multiple myeloma treatment. See related article by Degagné et al., p. 462 (2).
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Inmunoterapia Adoptiva/métodosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Acondicionamiento Pretrasplante , Trasplante Autólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células T Periférico/terapia , Acondicionamiento Pretrasplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Masculino , Persona de Mediana Edad , Femenino , Citarabina/administración & dosificación , Citarabina/farmacocinética , Citarabina/uso terapéutico , Carmustina/administración & dosificación , Carmustina/farmacocinética , Carmustina/uso terapéutico , Adulto , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Melfalán/farmacocinética , AncianoRESUMEN
Lenalidomide and rituximab (R2) is an effective frontline treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL). We investigated the safety and efficacy of addition of the proteasome inhibitor ixazomib to R2 for treatment of iNHL through a phase I/II clinical trial for high-risk patients. Twenty patients were enrolled, 18 were treated. The target dose of ixazomib 4 mg weekly was achieved during dose escalation. The most common treatment-related adverse events (AEs) were low grade gastrointestinal, rash, neuropathy, and myalgia/arthralgia. There were 33% grade 2 and 17% grade 3 infections. With median follow-up of 5.2 years, four patients discontinued treatment due to lymphoma progression. Best overall response rate (ORR) was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. Kaplan-Meier estimates of progression free and overall survival (OS) were 73% and 87% at 36 months, respectively. R2 can safely be combined with ixazomib for treatment-naïve iNHL patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos de Boro , Glicina , Lenalidomida , Linfoma Folicular , Rituximab , Humanos , Compuestos de Boro/uso terapéutico , Compuestos de Boro/administración & dosificación , Compuestos de Boro/efectos adversos , Glicina/análogos & derivados , Glicina/uso terapéutico , Glicina/efectos adversos , Glicina/administración & dosificación , Rituximab/efectos adversos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Lenalidomida/administración & dosificación , Lenalidomida/uso terapéutico , Lenalidomida/efectos adversos , Adulto , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/mortalidad , Resultado del Tratamiento , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Anciano de 80 o más AñosRESUMEN
CD19-targeting treatments have shown promise in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]) is a CD19-targeting antibody-drug conjugate indicated for R/R DLBCL after at least two systemic treatments. CD19 expression was evaluated in patients receiving Lonca in the LOTIS-2 clinical trial with available tissue samples obtained after last systemic therapy/before Lonca treatment. Lonca cytotoxicity was evaluated in a panel of six lymphoma cell lines with various CD19 expression levels. Quantitative systems pharmacology (QSP) modelling was used to predict Lonca responses. Lonca responses were seen in patients across all CD19 expression levels, including patients with low/no detectable CD19 expression and H-scores at baseline. Similarly, Lonca induced cytotoxicity in cell lines with different levels of CD19 expression, including one with very low expression. QSP modelling predicted that CD19 expression by immunohistochemistry alone does not predict Lonca response, whereas inclusion of CD19 surface density improved response prediction. Virtual patients responded to Lonca with estimated CD19 as low as 1000 molecules/cell of CD19, normally below the immunohistochemistry detection level. We found Lonca is an effective treatment for R/R DLBCL regardless of CD19 expression by immunohistochemistry. These results provide the basis for future studies addressing CD19-targeted agent sequencing.
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ABSTRACT: The curative potential of allogeneic hematopoietic transplantation (allo-HCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin, which has significant activity against ALL. We hypothesized that low-dose INO would be safe and feasible after allo-HCT. Therefore, we conducted a phase 1 study to determine the dose and safety in this setting. Patients were eligible if they were aged 16 to 75 years, had undergone allo-HCT for CD22+ ALL, were in complete remission (CR) after allo-HCT, had high risk of recurrence, were between day 40 and 100 after allo-HCT with adequate graft function, and did not have a history of sinusoidal obstruction syndrome (SOS). The objectives of this trial were to define INO maximum tolerated dose (MTD), to determine post-allo-HCT INO safety, and to measure 1-year progression-free survival (PFS). The trial design followed a "3+3" model. The treatment consisted of INO given on day 1 of 28-day cycles. Dose levels were 0.3 mg/m2, 0.4 mg/m2, 0.5 mg/m2, and 0.6 mg/m2. Median age was 44 years (range, 17-66 years; n = 18). Disease status at transplantation was first CR (n = 14) or second CR or beyond (n = 4). Preparative regimen was of reduced intensity in 72% of patients who received transplantation. Most common toxicity was thrombocytopenia. There were no instances of SOS; the MTD was 0.6 mg/m2. One-year nonrelapse mortality was 5.6%. With a median follow-up of 18.1 months (range, 8.6-59 months) 1-year post-allo-HCT PFS and overall survival is 89% and 94%, respectively. Low-dose INO has a favorable safety profile and was associated with high rates of 1-year PFS. This trial was registered at www.clinicaltrials.gov as #NCT03104491.
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Anticuerpos Monoclonales Humanizados , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adulto , Inotuzumab Ozogamicina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , RecurrenciaRESUMEN
ABSTRACT: Bispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS). The anticipated widespread use of these off-the-shelf products poses challenges for implementation and highlights the need for guidance in anticipating, mitigating, and managing adverse events. In clinical trials, guidance for the evaluation and treatment of CRS and neurotoxicity associated with BsAb therapy has been modeled after algorithms originally created for chimeric antigen receptor (CAR) T-cell therapies and other immune effector therapies, yet notable differences in timing, quality, and severity exist between the toxicities of BsAbs and CAR T-cell therapies. We therefore convened an international panel of academic and community practice physicians, advanced practitioners, registered nurses, and pharmacists with experience using CD3×CD20 BsAbs in clinical trial and off-trial settings to provide comprehensive, consensus-based recommendations specific to the assessment and management of CD3×CD20 BsAb-related toxicities.
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Anticuerpos Biespecíficos , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Consenso , Inmunoterapia Adoptiva/efectos adversos , Activación de LinfocitosRESUMEN
Therapies that demonstrate durable, long-term responses with manageable safety and tolerability are needed for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), an anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer, demonstrated single-agent antitumor activity in the pivotal phase II LOTIS-2 study in heavily pretreated patients with R/R DLBCL. Here we present updated efficacy and safety analyses from LOTIS-2, performed for all patients and in subsets of patients with a complete response (CR), including patients with CR who were event-free (no progressive disease or death) for ≥1 year and ≥2 years from cycle 1, day 1 of treatment. Lonca was administered every 3 weeks (0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles). As of the final data cutoff (September 15, 2022; median follow-up: 7.8 months [range, 0.3-42.6]), 70 of 145 (48.3%) patients achieved an overall response. Thirty-six (24.8%) patients achieved CR, of which 16 (44%) and 11 (31%) were event-free for ≥1 year and ≥2 years, respectively. In the all-treated population, the median overall survival was 9.5 months; the median progression-free survival was 4.9 months. Among patients with CR, median overall survival and progression-free survival were not reached, with 24-month overall and progression-free survival rates of 68.2% (95% CI: 50.0-81.0) and 72.5% (95% CI: 48.2-86.8), respectively. No new safety concerns were detected. With additional follow-up, Lonca continued to demonstrate durable, long-term responses with manageable safety and tolerability in patients with CR (clinicaltrials gov. Identifier: NCT03589469).
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Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Anticuerpos Monoclonales Humanizados , Benzodiazepinas , Linfoma de Células B Grandes Difuso/patologíaRESUMEN
PURPOSE: Significant progress has occurred in developing quantitative PET/CT biomarkers in diffuse large B-cell lymphoma (DLBCL). Total metabolic tumor volume (MTV) is the most extensively studied, enabling assessment of FDG-avid tumor burden associated with outcomes. However, prior studies evaluated the outcome of cytotoxic chemotherapy or chimeric antigen receptor T-cell therapy without data on recently approved FDA agents. Therefore, we aimed to assess the prognosis of PET/CT biomarkers in patients treated with loncastuximab tesirine. EXPERIMENTAL DESIGN: We centrally reviewed screening PET/CT scans of patients with relapsed/refractory DLBCL enrolled in the LOTIS-2 (NCT03589469) study. MTV was obtained by computing individual volumes using the SUV ≥4.0 threshold. Other PET/CT metrics, clinical factors, and the International Metabolic Prognostic Index (IMPI) were evaluated. Logistic regression was used to assess the association between biomarkers and treatment response. Cox regression was used to determine the effect of biomarkers on time-to-event outcomes. We estimated biomarker prediction as continuous and binary variables defined by cutoff points. RESULTS: Across 138 patients included in this study, MTV with a cutoff point of 96 mL was the biomarker associated with the highest predictive performance in univariable and multivariable models to predict failure to achieve complete metabolic response (OR, 5.42; P = 0.002), progression-free survival (HR, 2.68; P = 0.002), and overall survival (HR, 3.09; P < 0.0001). IMPI demonstrated an appropriate performance, however, not better than MTV alone. CONCLUSIONS: Pretreatment MTV demonstrated robust risk stratification, with those patients demonstrating high MTV achieving lower responses and survival to loncastuximab tesirine in relapsed/refractory DLBCL.
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Linfoma de Células B Grandes Difuso , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Biomarcadores , Fluorodesoxiglucosa F18 , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Carga Tumoral , Ensayos Clínicos como AsuntoRESUMEN
The available treatments for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have experienced a dramatic change since 2017. Incremental advances in basic and translational science over several decades have led to innovations in immune-oncology. These innovations have culminated in eight separate approvals by the US Food and Drug Administration for the treatment of patients with R/R DLBCL over the last 10 years. High-dose therapy and autologous stem cell transplant (HDT-ASCT) remains the standard of care for transplant-eligible patients who relapse after an initial remission. For transplant-ineligible patients or for those who relapse following HDT-ASCT, multiple options exist. Monoclonal antibodies targeting CD19, antibody-drug conjugates, bispecific antibodies, immune effector cell products, and other agents with novel mechanisms of action are now available for patients with R/R DLBCL. There is increasing use of chimeric antigen receptor (CAR) T-cells as second-line therapy for patients with early relapse of DLBCL or those who are refractory to initial chemoimmunotherapy. The clinical benefits of these strategies vary and are influenced by patient and disease characteristics, as well as the type of prior therapy administered. Therefore, there are multiple clinical scenarios that clinicians might encounter when treating R/R DLBCL. An optimal sequence of drugs has not been established, and there is no evidence-based consensus on how to best order these agents. This abundance of choices introduces a paradox: proliferating treatment options are initially a boon to patients and providers, but as choices grow further they no longer liberate. Rather, more choices make the management of R/R DLBCL more challenging due to lack of direct comparisons among agents and a desire to maximize patient outcomes. Here, we provide a review of recently-approved second- and subsequent-line agents, summarize real-world data detailing the use of these medicines, and provide a framework for sequencing therapy in R/R DLBCL.
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Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , RecurrenciaRESUMEN
Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.
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Linfoma Folicular , Linfoma de Células B Grandes Difuso , Linfoma de Células del Manto , Humanos , Adulto , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Inmunoterapia Adoptiva , Linfocitos TRESUMEN
Primary bone diffuse large B cell lymphoma (DLBCL) is a rare variant of extranodal non-Hodgkin lymphoma (NHL) historically treated with induction chemotherapy followed by consolidative radiation therapy (RT). It remains unknown whether RT confers additional benefit following rituximab-based chemoimmunotherapy (CIT) induction in patients with limited-stage disease. We conducted a multicenter retrospective analysis of patients treated between 2005 and 2019 using rituximab-based CIT regimens with or without consolidative RT to discern whether consolidative RT adds benefit in patients with stage I-II disease that could be encompassed in one radiation field. A total of 112 patients were included: 78 received CIT and radiation (RT group), and 34 received CIT alone (no RT group). The OS at 10 years was 77.9% in the RT group and 89.0% in the no RT group (p = 0.42). The RFS at 10 years was 73.5% in the RT group and 80.3% in the no RT group (p = 0.88). Neither improved OS nor RFS was associated with the addition of consolidative RT. Subgroup analysis of patients only achieving a partial response after CIT suggests that these patients may benefit from consolidative RT.
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Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively studied adults with newly diagnosed MCL treated from 2000 to 2015. Primary objectives were to describe progression-free survival (PFS) and overall survival (OS). Secondary objectives included characterization of patient characteristics and treatments. Of the 1029 patients with MCL studied, a total of 207 neoplasms were blastoid or pleomorphic variants. Median follow-up period was 82 months (range, 0.1-174 months); median PFS was 38 months (95% confidence interval [CI], 28-66) and OS was 68 months (95% CI, 45-96). Factors associated with PFS were receipt of consolidative autologous hematopoietic transplantation (auto-HCT; hazard ratio [HR], 0.52; 95% CI, 0.31-0.80; P < .05), MCL International Prognostic Index (MIPI) intermediate (HR, 2.3; 95% CI, 1.2-4.3; P < .02) and high (HR, 3.8; 95% CI, 2.0-7.4; P < .01) scores, and complete response to induction (HR, 0.29 (95% CI, 0.17-0.51). Receipt of auto-HCT was not associated with OS (HR, 0.69; 95% CI, 0.41-1.16; P = .16) but was associated with MIPI intermediate (HR, 5.7; 95% CI, 2.5-13.2; P < .01) and high (HR, 10.8; 95% CI, 4.7-24.9; P < .01) scores. We report outcomes in a large cohort of patients with blastoid/pleomorphic variant MCL. For eligible patients, receipt of auto-HCT after induction was associated with improved PFS but not OS. Higher MIPI score and auto-HCT ineligibility were associated with worse survival.
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Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/terapia , Linfoma de Células del Manto/tratamiento farmacológico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Medición de Riesgo , Supervivencia sin ProgresiónRESUMEN
Recently there has been a growing interest in evaluating body composition as a marker for prognosis in cancer patients. The association of body composition parameters and outcomes has not been deeply investigated in patients with autologous hematopoietic stem cell transplantation (HSCT) recipients with non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of 264 NHL patients who received autologous HSCT. PreHSCT abdominal CT scans at the levels of L3 were assessed for body composition measures. We evaluated sarcopenia, myosteatosis, high visceral adipose tissue (VAT) and high visceral adipose tissue density (VATD). Using multivariable Cox proportional regression, we analyzed the association of clinical and transplant-related characteristics with overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM). In a multivariate regression model, patients with higher VATD had worse OS (HR 1.78; 95% confidence intervals CI 1.08-2.95, p = 0.02) and worse NRM (HR 2.31 95% CI 1.08-4.95, p = 0.02) than with lower VATD. Patients with lower levels of VAT also had worse RFS (HR 1.49 95% CI 1.03-2.15, p = 0.03). Sarcopenia and myosteatosis were not associated with outcomes. High pre-transplant VATD was associated with lower OS and higher NRM, and low pre-transplant VAT was associated with worse RFS in patients with NHL undergoing autologous HSCT.
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Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Sarcopenia , Humanos , Estudios Retrospectivos , Sarcopenia/etiología , Recurrencia Local de Neoplasia , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/patología , Trasplante Autólogo , Composición CorporalRESUMEN
ABSTRACT: In this real-world evaluation of tafasitamab-lenalidomide (TL) in relapsed or refractory LBCL, patients receiving TL had higher rates of comorbidities and high-risk disease characteristics, and substantially lower progression-free survival and overall survival, compared with the L-MIND registration clinical trial for TL.