Hematological Oncology最新文献

{"title":"Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry","authors":"Pellegrino Musto,&nbsp;Jon Salmanton-García,&nbsp;Nicola Sgherza,&nbsp;Rui Bergantim,&nbsp;Francesca Farina,&nbsp;Andreas Glenthøj,&nbsp;Guldane Cengiz Seval,&nbsp;Barbora Weinbergerová,&nbsp;Valentina Bonuomo,&nbsp;Yavuz M. Bilgin,&nbsp;Jaap van Doesum,&nbsp;Ozren Jaksic,&nbsp;Benjamín Víšek,&nbsp;Iker Falces-Romero,&nbsp;Monia Marchetti,&nbsp;Julio Dávila-Valls,&nbsp;Sonia Martín-Pérez,&nbsp;Marcio Nucci,&nbsp;Alberto López-García,&nbsp;Federico Itri,&nbsp;Caterina Buquicchio,&nbsp;Luisa Verga,&nbsp;Klára Piukovics,&nbsp;Milan Navrátil,&nbsp;Graham P. Collins,&nbsp;Moraima Jiménez,&nbsp;Nicola S. Fracchiolla,&nbsp;Jorge Labrador,&nbsp;Lucia Prezioso,&nbsp;Elena Rossi,&nbsp;Natasha Čolović,&nbsp;Stef Meers,&nbsp;Austin Kulasekararaj,&nbsp;Annarosa Cuccaro,&nbsp;Ola Blennow,&nbsp;Toni Valković,&nbsp;Uluhan Sili,&nbsp;Marie-Pierre Ledoux,&nbsp;Josip Batinić,&nbsp;Francesco Passamonti,&nbsp;Marina Machado,&nbsp;Rafael F. Duarte,&nbsp;Christian Bjørn Poulsen,&nbsp;Gustavo-Adolfo Méndez,&nbsp;Ildefonso Espigado,&nbsp;Fatih Demirkan,&nbsp;Martin Čerňan,&nbsp;Chiara Cattaneo,&nbsp;Verena Petzer,&nbsp;Gabriele Magliano,&nbsp;Carolina Garcia-Vidal,&nbsp;Shaimaa El-Ashwah,&nbsp;Maria Gomes-Da-Silva,&nbsp;Antonio Vena,&nbsp;Irati Ormazabal-Vélez,&nbsp;Jens van Praet,&nbsp;Michelina Dargenio,&nbsp;Cristina De-Ramón,&nbsp;Maria Ilaria Del Principe,&nbsp;Joyce Marques-De-Almeida,&nbsp;Dominik Wolf,&nbsp;Tomáš Szotkowski,&nbsp;Aleš Obr,&nbsp;Gökçe Melis Çolak,&nbsp;Anna Nordlander,&nbsp;Macarena Izuzquiza,&nbsp;Alba Cabirta,&nbsp;Giovanni Paolo Maria Zambrotta,&nbsp;Raul Cordoba,&nbsp;Pavel Žák,&nbsp;Emanuele Ammatuna,&nbsp;Jiří Mayer,&nbsp;Osman Ilhan,&nbsp;Ramón García-Sanz,&nbsp;Martina Quattrone,&nbsp;Elena Arellano,&nbsp;Raquel Nunes-Rodrigues,&nbsp;Ziad Emarah,&nbsp;Tommaso Francesco Aiello,&nbsp;Michaela Hanakova,&nbsp;Zdeněk Ráčil,&nbsp;Martina Bavastro,&nbsp;Alessandro Limongelli,&nbsp;Laman Rahimli,&nbsp;Francesco Marchesi,&nbsp;Oliver A. Cornely,&nbsp;Livio Pagano","doi":"10.1002/hon.3240","DOIUrl":"10.1002/hon.3240","url":null,"abstract":"<p>Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 10⁹/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classic Hodgkin lymphoma","authors":"Justine Kahn,&nbsp;Bouthaina Dabaja,&nbsp;Susan Wu,&nbsp;Kara Kelly,&nbsp;Leanne Berkahn,&nbsp;Astrid Pavlovsky,&nbsp;Anna Sureda,&nbsp;Ann LaCasce","doi":"10.1002/hon.3239","DOIUrl":"10.1002/hon.3239","url":null,"abstract":"<p>Classic Hodgkin lymphoma (HL) is rare disease, with an incidence of approximately 85,000 patients globally per year and a predilection for adolescents and young adults (ages 15–39). Since the introduction of combination chemotherapy in the 1960's and radiation dating back to the early 1900's, therapeutic options and by extension, clinical outcomes have improved dramatically with 5-year overall survival (OS) approaching 90% today. [1](#ref-0001) Advances in understanding HL biology have additionally facilitated development of targeted agents and immunotherapy which have further improved short and long-term outcomes. Despite continued improvements in up-front and salvage therapy, long-term survivors of HL experience several treatment-associated late toxicities, thus, along with efforts to improve therapeutic efficacy, efforts to reduce late effects remain a high-priority in the field.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138459531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early intervention of extracorporeal photopheresis for advancing/progressing cutaneous T-cell lymphoma","authors":"Daniel Aires,&nbsp;Sunil Abhyankar","doi":"10.1002/hon.3229","DOIUrl":"10.1002/hon.3229","url":null,"abstract":"<p>Patients with cutaneous T-cell lymphoma with progressive disease typically undergo a series of skin-directed and systemic therapy regimens during cycles of response and relapse. Extracorporeal photopheresis (ECP) is an effective and safe systemic treatment option, often reserved for later stages of disease and typically employed after failure of several other therapies. ECP has benefits in response rate, time to next treatment, and tolerability that may support its use earlier in the treatment cycle for advancing/progressing disease.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136397226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A low total metabolic tumor volume independently predicts for a longer time to first treatment in initially observed, low tumor burden follicular lymphoma","authors":"Pablo Mozas,&nbsp;Sebastian Casanueva-Eliceiry,&nbsp;Andrea Rivero,&nbsp;Ángel Serna,&nbsp;Marc Simó,&nbsp;Sonia Rodríguez,&nbsp;Alfredo Rivas-Delgado,&nbsp;Ferran Nadeu,&nbsp;Juan Gonzalo Correa,&nbsp;Juan Antonio Piñeyroa,&nbsp;Amanda Isabel Pérez-Valencia,&nbsp;Katia Guinetti-Ortiz,&nbsp;Marta Gómez-Hernando,&nbsp;Eva Giné,&nbsp;Julio Delgado,&nbsp;Neus Villamor,&nbsp;Elías Campo,&nbsp;Laura Magnano,&nbsp;Pau Abrisqueta,&nbsp;Xavier Setoain,&nbsp;Armando López-Guillermo","doi":"10.1002/hon.3235","DOIUrl":"10.1002/hon.3235","url":null,"abstract":"<p>Watchful waiting is an acceptable management strategy for advanced-stage, low tumor burden (LTB) patients with follicular lymphoma (FL). However, the prediction of how long this treatment-free observation period will last remains imperfect. We explored whether total metabolic tumor volume (TMTV) and other positron emission tomography parameters were predictive of time to first treatment (TTFT). We analyzed 97 grade 1–3A advanced-stage LTB FL patients and found that a high TMTV was associated with other tumor burden features at diagnosis. Patients with a TMTV above our established cutoff of 50 mL had a significantly shorter median duration of observation (2.6 vs. 8.8 years; <i>p</i> = 0.001). At 5 years, 77% of patients with a high TMTV and 46% of patients with a low TMTV required treatment. In the multivariable analysis, a high TMTV was the only independent factor predicting TTFT (hazard ratio = 2.09; <i>p</i> = 0.017). Overall, TMTV is a strong predictor of the duration of observation in LTB FL patients. Upon validation of our cutoff in external series and standardization of the methodology, the TMTV could become an additional factor to consider deferring or initiating treatment in otherwise LTB patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to integrate CD19 specific chimeric antigen receptor T cells with other CD19 targeting agents in diffuse large B-cell lymphoma?","authors":"Carmen de Ramon Ortiz,&nbsp;Sisi Wang,&nbsp;Anastasios Stathis,&nbsp;Francesco Bertoni,&nbsp;Thorsten Zenz,&nbsp;Urban Novak,&nbsp;Federico Simonetta","doi":"10.1002/hon.3237","DOIUrl":"10.1002/hon.3237","url":null,"abstract":"<p>About one third of patients with diffuse large B-cell lymphoma (DLBCL) have a relapsing/refractory (R/R) disease after first line chemo-immunotherapy, with particularly poor outcomes observed in patients with primary refractory disease and early relapse. CD19 specific chimeric antigen receptor (CAR) T cell therapy is a game changer that results in durable and complete response rates in almost half of the patients with R/R DLBCL. Other emerging CD19-targeting therapies include monoclonal antibodies, bispecific antibodies and targeting antibody-drug conjugates, which also show encouraging results. However, the timing and sequencing of different anti-CD19-targeting agents and how they might interfere with subsequent CAR T cell treatment is still unclear. In this review, we summarize the results of the pivotal clinical trials as well as evidence from real-world series of the use of different CD19-targeting approved agents. We discuss the effect of various therapies on CD19 expression and its implications for treatment sequencing.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting TP53 disruption in chronic lymphocytic leukemia: Current strategies and future directions","authors":"Stefano Molica,&nbsp;Constantine Tam,&nbsp;David Allsup,&nbsp;Aaron Polliack","doi":"10.1002/hon.3238","DOIUrl":"10.1002/hon.3238","url":null,"abstract":"<p>In the modern era of Chronic Lymphocytic Leukemia (CLL) targeted therapy, the loss of p53 function due to genetic abnormalities remains a significant challenge. This is because even targeted agents, which are currently the mainstay of treatment for CLL, do not directly target p53 or restore its disrupted pathway. Consequently, resistance to therapy and unfavorable clinical outcomes often accompany these p53-related abnormalities. An essential goal of future clinical research should be to address the ostensibly “undruggable” p53 pathway. Currently, multiple therapeutic approaches are being explored to tackle <i>TP53</i> dysfunction and improve outcomes in high-risk CLL. These approaches include the use of oncoprotein murine double minute 2 inhibitors, small-molecule p53 reactivators, exportin 1 (XPO1) inhibitors, and ataxia-telangiectasia mutated and Rad3-related (ATR) inhibitors. Combinations of these p53-targeting strategies, along with established novel therapies such as B-cell receptor or B-cell lymphoma-2 (BCL-2) inhibitors, may shape the future of therapeutic trials in this challenging-to-treat disease.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase II study of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed or refractory non-Hodgkin lymphoma","authors":"Yoshikazu Ikoma,&nbsp;Nobuhiko Nakamura,&nbsp;Junichi Kitagawa,&nbsp;Takao Miwa,&nbsp;Eri Takada,&nbsp;Takuro Matsumoto,&nbsp;Yuhei Shibata,&nbsp;Hiroshi Nakamura,&nbsp;Nobuhiro Kanemura,&nbsp;Senji Kasahara,&nbsp;Takeshi Hara,&nbsp;Michio Sawada,&nbsp;Hisashi Tsurumi,&nbsp;Masahito Shimizu","doi":"10.1002/hon.3236","DOIUrl":"10.1002/hon.3236","url":null,"abstract":"<p>This study evaluated the efficacy and safety of salvage chemotherapy with gemcitabine, carboplatin, dexamethasone, and rituximab (GCD ± R) for Japanese patients with relapsed or refractory non-Hodgkin lymphoma (NHL). A multicenter, phase II trial of GCD ± R administered every 3 weeks for up to 6 cycles was conducted. Rituximab was administered as a therapeutic strategy for CD20-positive lymphoma. The primary endpoint was the complete response (CR) rate. Secondary endpoints included the overall response (OR) rate, overall survival (OS), progression-free survival (PFS), toxicity, and success rate of peripheral blood stem cell collection for eligible transplant patients. A total of 25 patients (median age 66 years) were evaluated, with a median follow-up period of 66.7 months. CR and OR rates were 28% and 52%, respectively. Median PFS and OS were 8.7 and 32.2 months, respectively. The major toxicity was myelosuppression, but the regimen was generally well-tolerated, with a low incidence of febrile neutropenia (20%) and no treatment-related deaths. Of the 6 patients who were eligible for autologous stem cell transplantation and underwent peripheral blood stem cell mobilization, the required number of CD34-positive cells was collected in 5 (83%). All 6 proceeded to transplantation and achieved successful engraftment without recurrence. The present results suggest that GCD ± R may be effective and well-tolerated in Japanese patients with relapsed or refractory NHL. However, further investigation is needed to confirm these results.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dependence of peripheral T-cell lymphoma on constitutively activated JAK3: Implication for JAK3 inhibition as a therapeutic approach","authors":"Kang Le,&nbsp;Jordan Vollenweider,&nbsp;JingJing Han,&nbsp;Nicholas Staudinger,&nbsp;Mary Stenson,&nbsp;Lara Bayraktar,&nbsp;Linda E. Wellik,&nbsp;Matthew J. Maurer,&nbsp;Ellen D. McPhail,&nbsp;Thomas E. Witzig,&nbsp;Mamta Gupta","doi":"10.1002/hon.3233","DOIUrl":"10.1002/hon.3233","url":null,"abstract":"<p>Peripheral T-cell lymphoma (PTCL) is a clinically heterogeneous group that represents 10%–15% of all lymphomas. Despite improved genetic and molecular understanding, treatment outcomes for PTCL have not shown significant improvement. Although Janus kinase-2 (JAK2) plays an important role in myeloproliferative neoplasms, the critical role of JAK isoforms in mediating prosurvival signaling in PTCL cells is not well defined. Immunohistochemical analysis of PTCL tumors (<i>n</i> = 96) revealed high levels of constitutively active JAK3 (pJAK3) that significantly (<i>p</i> &lt; 0.04) correlated with the activation state of its canonical substrate STAT3. Furthermore, constitutive activation of JAK3 and STAT3 positively correlated, at least in part, with an oncogenic tyrosine phosphatase PTPN11. Pharmacological inhibition of JAK3 but not JAK1/JAK2 significantly (<i>p</i> &lt; 0.001) decreased PTCL proliferation, survival and STAT3 activation. A sharp contrast was observed in the pJAK3 positivity between ALK+ (85.7%) versus ALK-negative (10.0%) in human PTCL tumors and PTCL cell lines. Moreover, JAK3 and ALK reciprocally interacted in PTCL cells, forming a complex to possibly regulate STAT3 signaling. Finally, combined inhibition of JAK3 (by WHI-P154) and ALK (by crizotinib or alectinib) significantly (<i>p</i> &lt; 0.01) decreased the survival of PTCL cells as compared to either agent alone by inhibiting STAT3 downstream signaling. Collectively, our findings establish that JAK3 is a therapeutic target for a subset of PTCL, and provide rationale for the clinical evaluation of JAK3 inhibitors combined with ALK-targeted therapy in PTCL.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50157689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tagraxofusp in myeloid malignancies","authors":"Antonella Bruzzese,&nbsp;Enrica Antonia Martino,&nbsp;Caterina Labanca,&nbsp;Francesco Mendicino,&nbsp;Eugenio Lucia,&nbsp;Virginia Olivito,&nbsp;Antonino Neri,&nbsp;Annalisa Imovilli,&nbsp;Fortunato Morabito,&nbsp;Ernesto Vigna,&nbsp;Massimo Gentile","doi":"10.1002/hon.3234","DOIUrl":"10.1002/hon.3234","url":null,"abstract":"<p>Tagraxofusp (or SL-401) is a recombinant molecule composed of human interleukin-3 that binds CD123 on neoplastic cells fused to a truncated diphtheria toxin (DT). Tagraxofusp's most significant success has come from studies involving patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive disease that is usually refractory to conventional chemotherapy. Tagraxofusp had an acceptable safety profile and high efficacy in early phase I/II studies on patients with BPDCN. Another phase II study confirmed the good response rates, resulting in Food and Drugs Administration and European Medicine Agency approval of tagraxofusp for the treatment of BPDCN. Considering its high efficacy and its manageable safety profile, tagraxofusp has been suddenly explored in other myeloid malignancies with high expression of cell surface CD123, both in monotherapy or combination strategies. The triplet tagraxofusp-azacytidine-venetoclax appears to be of particular interest among these combinations. Furthermore, combination strategies may be used to overcome tagraxofusp resistance. The downregulation of DPH1 (diphthamide biosynthesis 1), the enzyme responsible for the conversion of histidine 715 on eEF2 to diphthamide, which is then the direct target of ADP ribosylation DT, is typically associated with this resistance phenomenon. It has been discovered that azacitidine can reverse DHP1 expression and restore sensitivity to tagraxofusp. In conclusion, the success of tagraxofusp in BPDCN paved the way for its application even in other CD123-positive malignancies. Nowadays, several ongoing trials are exploring the use of tagraxofusp in different myeloid neoplasms. This review aims to summarize the actual role of tagraxofusp in BPDCN and other CD123-positive myeloid malignancies.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41234626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic parameters predict survival and toxicity in chimeric antigen receptor T-cell therapy-treated relapsed/refractory large B-cell lymphoma","authors":"Hazim S. Ababneh,&nbsp;Andrea K. Ng,&nbsp;Jeremy S. Abramson,&nbsp;Jacob D. Soumerai,&nbsp;Ronald W. Takvorian,&nbsp;Matthew J. Frigault,&nbsp;Chirayu G. Patel","doi":"10.1002/hon.3231","DOIUrl":"10.1002/hon.3231","url":null,"abstract":"<p>CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL). However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited. Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10.7 months [interquartile range (IQR): 2.6–25.5 months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (<i>n</i> = 45) and 53% (<i>n</i> = 31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR = 4.7, <i>p</i> = 0.01, OR = 9.5, <i>p</i> = 0.03, respectively) and CR post-CAR T (OR = 12.4, <i>p</i> = 0.0004, OR = 10.9, <i>p</i> = 0.0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR = 3.25, <i>p</i> = 0.04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR = 4.3, <i>p</i> = 0.01), and high SUV pre-CAR T was associated with grade 3–4 neurological events (OR = 12, <i>p</i> = 0.01). High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). On multivariate analysis, high TLG pre-CAR T (HR = 2.4, <i>p</i> = 0.03), age ≥60 (HR = 2.7, <i>p</i> = 0.03), and bulky disease (≥5 cm) at the time of apheresis (HR = 2.5, <i>p</i> = 0.02) were identified to be independent prognostic factors for inferior PFS. High MTV post-CAR T was identified as the most prognostic factor associated with inferior OS.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}