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351. Pretreatment SUVmax may influence the clinical benefit of BR over R-CHOP in patients with previously untreated FL

Author

Strati, Paolo, primary, Ahmed, Mohamed Amin, additional, Nastoupil, Loretta J., additional, Feng, Lei, additional, Hagemeister, Fredrick B., additional, Fayad, Luis E., additional, Rodriguez, Maria A., additional, Samaniego, Felipe, additional, Wang, Michael, additional, Westin, Jason R., additional, Lee, Hun J., additional, Iyer, Swaminathan P., additional, Parmar, Simrit, additional, Ahmed, Sairah, additional, Nair, Ranjit, additional, Steiner, Raphael E., additional, Noorani, Mansoor, additional, Flowers, Christopher R., additional, Davis, R. Eric, additional, Fowler, Nathan H., additional, and Neelapu, Sattva S., additional

Published
2020
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352. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Author

Sehn, Laurie H., primary, Herrera, Alex F., additional, Flowers, Christopher R., additional, Kamdar, Manali K., additional, McMillan, Andrew, additional, Hertzberg, Mark, additional, Assouline, Sarit, additional, Kim, Tae Min, additional, Kim, Won Seog, additional, Ozcan, Muhit, additional, Hirata, Jamie, additional, Penuel, Elicia, additional, Paulson, Joseph N., additional, Cheng, Ji, additional, Ku, Grace, additional, and Matasar, Matthew J., additional

Published
2020
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354. Receiver operating characteristic curve analysis of circulating blood dendritic cell precursors and T cells predicts response to extracorporeal photopheresis in patients with chronic graft-versus-host disease

Author

Akhtari, Mojtaba, Giver, Cynthia R., Ali, Zahir, Flowers, Christopher R., Gleason, Charise L., Hillyer, Christopher D., Kaufman, Jonathan, Khoury, Jean H., Langston, Amelia A., Lechowicz, Mary Jo, Lonial, Sagar, Renfroe, Heather M., Roback, John D., Tighiouart, Mourad, Vaughn, Louette, and Waller, Edmund K.

Published
2010
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355. Improving outcomes for patients with diffuse large B-cell lymphoma

Author

Flowers, Christopher R., Sinha, Rajni, and Vose, Julie M.

Subjects
Non-Hodgkin's lymphomas -- Diagnosis, Non-Hodgkin's lymphomas -- Care and treatment, Non-Hodgkin's lymphomas -- Patient outcomes, Non-Hodgkin's lymphomas -- Risk factors, Health
Published
2010

356. A prospective study on early PET/CT scans during the first cycle of salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.

Author

Cherng, Hua-Jay J., Chuang, Hubert H., Steiner, Raphael, Fayad, Luis, Strati, Paolo, Nair, Ranjit, Hagemeister, Fredrick, Nastoupil, Loretta J., Lee, Hun Ju, Neelapu, Sattva S., Flowers, Christopher R., Samaniego, Felipe, Rodriguez, Maria, Macapinlac, Homer A., Feng, Lei, and Westin, Jason

Subjects
DIFFUSE large B-cell lymphomas, COMPUTED tomography, LONGITUDINAL method, SALVAGE therapy, CANCER chemotherapy
Abstract

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 (p = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments. [ABSTRACT FROM AUTHOR]

Published
2022
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358. Early drug development in solid tumours: analysis of National Cancer Institute-sponsored phase 1 trials

Author

Chihara, Dai, Lin, Ruitao, Flowers, Christopher R, Finnigan, Shanda R, Cordes, Lisa M, Fukuda, Yoko, Huang, Erich P, Rubinstein, Larry V, Nastoupil, Loretta J, Ivy, S Percy, Doroshow, James H, and Takebe, Naoko

Abstract

The low expectation of clinical benefit from phase 1 cancer therapeutics trials might negatively affect patient and physician participation, study reimbursement, and slow the progress of oncology research. Advances in cancer drug development, meanwhile, might have favourably improved treatment responses; however, little comprehensive data exist describing the response and toxicity associated with phase 1 trials across solid tumours. The aim of the study is to evaluate the trend of toxicity and response in phase 1 trials for solid tumours over time.

Published
2022
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359. Evaluating the impact of eligibility criteria in first-line clinical trials for follicular lymphoma: a MER/LEO cohort analysis

Author

Luan, Danny, Fatola, Tolulope, Toure, Ahmed, Flowers, Christopher R., Link, Brian, Friedberg, Jonathan W., Cohen, Jonathon B., Kahl, Brad, Lossos, Izidore S., Nastoupil, Loretta, Maurer, Matthew J., Cerhan, James R., and Martin, Peter

Abstract

Cancer clinical trial eligibility criteria may create patient populations studied in trials that do not reflect the patient populations treated in the real-world setting. Follicular lymphoma (FL) is an indolent lymphoma with heterogeneous presentations across a broad range of individuals, resulting in many acceptable management strategies. We evaluated how first-line clinical trial eligibility criteria impacted the demographic makeup and outcomes of patients with FL for whom systemic therapy might be considered. We compared the characteristics of 196 patients with FL from a single institution to eligibility criteria from 10 first-line FL trials on clinicaltrials.gov. Next, we tabulated eligibility criteria from 24 first-line FL protocols and evaluated their impact on 1198 patients with FL with stages II to IV disease from the prospective Molecular Epidemiology Resource (MER) and Lymphoma Epidemiology of Outcomes (LEO) cohort studies. We found that 39.8% and 52.7% of patients with FL might be excluded from clinical trials based on eligibility criteria derived from clinicaltrials.gov and protocol documents, respectively. Patients excluded because of renal function, prior malignancy, and self-reported serious health conditions tended to be older. Expanding stage requirement from III-IV to II-IV, and platelet requirement from ≥150 000 to ≥75 000 increased population size by 21% and 8%, respectively, in MER and by 16% and 13%, respectively, in LEO, without impacting patient demographics or outcomes. These data suggest that management of older individuals with FL may not be fully informed by recent clinical trials. Moreover, liberalizing stage and platelet criteria might expand the eligible population and allow for quicker trial accrual without impacting outcomes.

Published
2022
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360. Risk assessment with low-pass whole-genome sequencing of cell-free DNA before CD19 CAR T-cell therapy for large B-cell lymphoma

Author

Cherng, Hua-Jay J., Sun, Ryan, Sugg, Bryant, Irwin, Russell, Yang, Haopeng, Le, Cao Cuong, Deng, Qing, Fayad, Luis, Fowler, Nathan H., Parmar, Simrit, Steiner, Raphael, Hagemeister, Fredrick, Nair, Ranjit, Lee, Hun Ju, Rodriguez, Maria, Samaniego, Felipe, Iyer, Swaminathan P., Flowers, Christopher R., Wang, Linghua, Nastoupil, Loretta J., Neelapu, Sattva S., Ahmed, Sairah, Strati, Paolo, Green, Michael R., and Westin, Jason

Abstract

Patients with relapsed or refractory large B-cell lymphomas (rrLBCL) can achieve long-term remission after CD19 chimeric antigen receptor T-cell therapy (CART19). However, more than half of recipients will experience treatment failure. Thus, approaches are needed to identify high-risk patients who may benefit from alternative or consolidative therapy. We evaluated low-pass whole-genome sequencing (lpWGS) of cell-free DNA (cfDNA) before CART19 as a new approach for risk stratification. We performed lpWGS on pretreatment plasma samples from 122 patients at time of leukapheresis who received standard-of-care CART19 for rrLBCL to define DNA copy number alterations (CNAs). In multivariable selection, high focal CNA score (FCS) denoting genomic instability was the most significant pretreatment variable associated with inferior 3-month complete response rates (28% vs 56%, P = .0029), progression-free survival (PFS; P = .0007; hazard ratio, 2.11), and overall survival (OS; P = .0026; hazard ratio, 2.10). We identified 34 unique focal CNAs in 108 (89%) patients; of these, deletion 10q23.3 leading to loss of FAS death receptor was the most highly associated with poor outcomes, leading to inferior PFS (P < .0001; hazard ratio, 3.49) and OS (P = .0027; hazard ratio, 2.68). By combining FCS with traditional markers of increased tumor bulk (elevated lactate dehydrogenase and >1 extranodal site), we built a simple risk model that could reliably risk stratify patients. Thus, lpWGS of cfDNA is a minimally invasive assay that could rapidly identify high-risk patients and may guide patient selection for and targeted therapies to evaluate in future clinical trials.

Published
2022
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364. Pathogen Molecular Pattern Receptor Agonists: Treating Cancer by Mimicking Infection

Author

Aleynick, Mark, Svensson-Arvelund, Judit, Flowers, Christopher R., Marabelle, Aurélien, Brody, Joshua D., Aleynick, Mark, Svensson-Arvelund, Judit, Flowers, Christopher R., Marabelle, Aurélien, and Brody, Joshua D.

Abstract

mmunotherapies such as checkpoint blockade have achieved durable benefits for patients with advanced stage cancer and have changed treatment paradigms. However, these therapies rely on a patient's own a priori primed tumor-specific T cells, limiting their efficacy to a subset of patients. Because checkpoint blockade is most effective in patients with inflamed or "hot" tumors, a priority in the field is learning how to "turn cold tumors hot." Inflammation is generally initiated by innate immune cells, which receive signals through pattern recognition receptors (PRR)–a diverse family of receptors that sense conserved molecular patterns on pathogens, alarming the immune system of an invading microbe. Their immunostimulatory properties can reprogram the immune suppressive tumor microenvironment and activate antigen-presenting cells to present tumors antigens, driving de novo tumor-specific T-cell responses. These features, among others, make PRR-targeting therapies an attractive strategy in immuno-oncology. Here, we discuss mechanisms of PRR activation, highlighting ongoing clinical trials and recent preclinical advances focused on therapeutically targeting PRRs to treat cancer.

Published
2019
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365. SIRPα+macrophages are increased in patients with FL who progress or relapse after frontline lenalidomide and rituximab

Author

Marques-Piubelli, Mario L., Parra, Edwin R., Feng, Lei, Soto, Luisa Solis, Gallardo, Mariana, Gouni, Sushanth, Samaniego, Felipe, Noorani, Mansoor, Hagemeister, Fredrick B., Westin, Jason R., Lee, Hun Ju, Rodriguez, Maria A., Neelapu, Sattva S., Gunther, Jillian R., Fowler, Nathan H., Flowers, Christopher R., Wistuba, Ignacio I., Nastoupil, Loretta J., Vega, Francisco, and Strati, Paolo

Abstract

Limited data exist regarding the outcome of patients with follicular lymphoma (FL) who relapse or progress after frontline lenalidomide and rituximab (R2). Moreover, mechanisms of resistance to R2in FL remain unclear, with increased protumoral macrophages suspected as a major contributory culprit to this phenomenon. This retrospective study analyzed the outcome of patients with advanced-stage FL grade 1 to 3A who relapsed or progressed after frontline R2. A multiplex immunofluorescence macrophage panel, including CD47, CD14, CD68, CD115 (also known as colony-stimulating factor 1 receptor [CSF1R]), CD163, CD172a (also known as signal regulatory protein α [SIRPα]), and CD274 (also known as programmed cell death-ligand 1 [PDL1]), was used to stain tissue biopsy specimens collected before initiation of R2and at the time of progression. Among 156 patients with advanced-stage FL treated with frontline R2, 33 (21%) relapsed or progressed and required second-line therapy, after a median of 33 months (range, 1-122 months). Second-line therapy was chemoimmunotherapy in 16 (48%) patients and other therapy in 17 (52%). The overall response rate was 78%, and complete response rate was 72%. Median progression-free survival was significantly longer in patients who received chemoimmunotherapy compared with other therapy (99 vs 25 months; P= .004). Three macrophage populations were significantly increased in tissue samples collected at progression compared with before frontline treatment: CD68+CD115+(P= .02), CD68+CD115+CD172a+(P= .02), and CD68+CD163+CD172a+(P= .01). Chemoimmunotherapy is an effective treatment strategy for patients with FL who relapse after frontline R2. Therapies targeting specific macrophage populations may yield novel approaches for improving outcomes with frontline R2.

Published
2022
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366. SIRPα+ macrophages are increased in patients with FL who progress or relapse after frontline lenalidomide and rituximab

Author

Marques-Piubelli, Mario L., Parra, Edwin R., Feng, Lei, Soto, Luisa Solis, Gallardo, Mariana, Gouni, Sushanth, Samaniego, Felipe, Noorani, Mansoor, Hagemeister, Fredrick B., Westin, Jason R., Lee, Hun Ju, Rodriguez, Maria A., Neelapu, Sattva S., Gunther, Jillian R., Fowler, Nathan H., Flowers, Christopher R., Wistuba, Ignacio I., Nastoupil, Loretta J., Vega, Francisco, and Strati, Paolo

Abstract

Limited data exist regarding the outcome of patients with follicular lymphoma (FL) who relapse or progress after frontline lenalidomide and rituximab (R2). Moreover, mechanisms of resistance to R2 in FL remain unclear, with increased protumoral macrophages suspected as a major contributory culprit to this phenomenon. This retrospective study analyzed the outcome of patients with advanced-stage FL grade 1 to 3A who relapsed or progressed after frontline R2. A multiplex immunofluorescence macrophage panel, including CD47, CD14, CD68, CD115 (also known as colony-stimulating factor 1 receptor [CSF1R]), CD163, CD172a (also known as signal regulatory protein α [SIRPα]), and CD274 (also known as programmed cell death-ligand 1 [PDL1]), was used to stain tissue biopsy specimens collected before initiation of R2 and at the time of progression. Among 156 patients with advanced-stage FL treated with frontline R2, 33 (21%) relapsed or progressed and required second-line therapy, after a median of 33 months (range, 1-122 months). Second-line therapy was chemoimmunotherapy in 16 (48%) patients and other therapy in 17 (52%). The overall response rate was 78%, and complete response rate was 72%. Median progression-free survival was significantly longer in patients who received chemoimmunotherapy compared with other therapy (99 vs 25 months; P = .004). Three macrophage populations were significantly increased in tissue samples collected at progression compared with before frontline treatment: CD68+CD115+ (P = .02), CD68+CD115+CD172a+ (P = .02), and CD68+CD163+CD172a+ (P = .01). Chemoimmunotherapy is an effective treatment strategy for patients with FL who relapse after frontline R2. Therapies targeting specific macrophage populations may yield novel approaches for improving outcomes with frontline R2.

Published
2022
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367. Improving eligibility criteria for first-line trials for patients with DLBCL using a US-based Delphi-method survey

Author

Harkins, R. Andrew, Patel, Sharvil P., Lee, Michelle J., Switchenko, Jeffrey M., Ansell, Stephen M., Bartlett, Nancy L., Blum, Kristie A., Cashen, Amanda F., Casulo, Carla, Friedberg, Jonathan W., Johnston, Patrick B., Kahl, Brad S., Leonard, John P., Link, Brian K., Lossos, Izidore S., Martin, Peter, Maurer, Matt J., Mehta-Shah, Neha, Reagan, Patrick M., Westin, Jason R., Koff, Jean L., and Flowers, Christopher R.

Abstract

Recent first-line randomized controlled trials (RCTs) for patients with diffuse large B-cell lymphoma (DLBCL) have shown negative results, which may be due in part to onerous eligibility criteria limiting enrollment of poor-risk patients who require immediate treatment. We conducted a Delphi-method survey with lymphoma experts in the United States to define recommendations for essential and potentially unnecessary enrollment criteria for modern first-line DLBCL RCTs aimed at increasing clinical diversity of ensuing study groups. We first tabulated enrollment criteria from 19 DLBCL RCTs spanning the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) era to identify common eligibility criteria from prior DLBCL RCTs for inclusion in the Delphi-method survey. We tabulated 451 total eligibility criteria comprising 51 criterion categories across 19 first-line DLBCL RCTs in the R-CHOP era. We then surveyed lymphoma clinical trial experts representing 8 academic medical centers in the United States regarding essential and unnecessary eligibility criteria for modern DLBCL RCTs. Seventeen of 29 invited clinical investigators completed the round-1 questionnaire (response rate, of 58.6%), 15 of 17 round-1 participants (88.2%) completed the round-2 survey, and all round-1 participants reviewed finalized recommendations for eligibility criteria for modern first-line DLBCL RCTs. We defined consensus recommendations for 31 modernized eligibility criteria including threshold values for 10 quantitative eligibility criteria aimed at facilitating enrollment of a clinically diverse study population in first-line DLBCL RCTs designed to improve standard-of-care therapy.

Published
2022
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368. Day 30 SUVmaxpredicts progression in patients with lymphoma achieving PR/SD after CAR T-cell therapy

Author

Al Zaki, Ajlan, Feng, Lei, Watson, Grace, Ahmed, Sairah A., Mistry, Haleigh, Nastoupil, Loretta J., Hawkins, Misha, Nair, Ranjit, Iyer, Swaminathan P., Lee, Hun J., Steiner, Raphael E., Flowers, Christopher R., Shpall, Elizabeth J., Kebriaei, Partow, Neelapu, Sattva S., Westin, Jason R., and Strati, Paolo

Abstract

About 70% of patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel) and who achieve a partial response (PR) or stable disease (SD) on the day 30 (D30) positron emission tomography (PET)–computed tomography (CT) scan progress; however, the factors that are predictive of progression are unknown. This a retrospective study of patients with LBCL who were treated with axi-cel at MD Anderson Cancer Center between January of 2018 and February of 2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to a complete response (CR). Among 95 patients with a D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day −5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (P= .05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was a lower maximum standardized uptake volume (SUVmax; P< .001); all patients with D30 SUVmax≥ 10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed between patients who converted from D30 PR/SD to subsequent CR and those who had been in CR since D30 (P= .19). Novel predictive and prognostic markers based on tissue biopsy and noninvasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.

Published
2022
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369. Autologous stem cell transplantation for large B-cell lymphoma with secondary central nervous system involvement

Author

Akin, Serkan, Hosing, Chitra, Khouri, Issa, Ahmed, Sairah, Alousi, Amin, Fowler, Nathan, Joseph, Jacinth, Truxillo, Jonathan, Ramdial, Jeremy L., Maadani, Farzaneh, Rondon, Gabriela, Daher, May, Im, Jin S., Steiner, Raphael, Westin, Jason, Iyer, Swaminathan P., Dabaja, Bouthaina, Anderlini, Paolo, Popat, Uday R., Qazilbash, Muzaffar H., Flowers, Christopher R., Shpall, Elizabeth, Champlin, Richard E., Nieto, Yago, and Srour, Samer A.

Abstract

Secondary central nervous system large B-cell lymphoma (SCNSL) is rare, with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression-free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal lactate dehydrogenase, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (hazard ratio [HR], 0.278; 95% CI, 0.153-0.506; P≤ .0001) and ≤2 prior lines of therapy (HR, 0.485; 95% CI, 0.274-0.859; P= .0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR, 0.352; 95% CI, 0.186-0.663; P= .0013) and ≤2 prior lines of therapy (HR, 0.476; 95% CI, 0.257-0.882; P= .0183) were associated with improved survival. In the largest single-center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those who received ≤2 lines of therapy have particularly excellent outcomes.

Published
2022
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370. Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study

Author

Casulo, Carla, Larson, Melissa C, Lunde, Julianne J, Habermann, Thomas M, Lossos, Izidore S, Wang, Yucai, Nastoupil, Loretta J, Strouse, Christopher, Chihara, Dai, Martin, Peter, Cohen, Jonathon B, Kahl, Brad S, Burack, W Richard, Koff, Jean L, Mun, Yong, Masaquel, Anthony, Wu, Mei, Wei, Michael C, Shewade, Ashwini, Li, Jia, Cerhan, James, Flowers, Christopher R, Link, Brian K, and Maurer, Matthew J

Abstract

Novel therapies for relapsed or refractory follicular lymphoma are commonly evaluated in single-arm studies without formal comparison with other treatments or historical controls. Consequently, rigorously defined treatment outcomes informing expectations for novel therapeutic strategies in this population are sparse. To inform outcome expectations, we aimed to describe treatment patterns, survival outcomes, and duration of response in patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy.

Published
2022
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371. HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

Author

Wang, Sophia S., Carrington, Mary, Berndt, Sonja I., Slager, Susan L., Bracci, Paige M., Voutsinas, Jenna, Cerhan, James R., Ekström Smedby, Karin, Hjalgrim, Henrik, Vijai, Joseph, Morton, Lindsay M., Vermeulen, Roel, Paltiel, Ora, Vajdic, Claire M, Linet, Martha S., Nieters, Alexandra, de Sanjosé, Silvia, Cozen, Wendy, Brown, Elizabeth E., Turner, Jennifer, Spinelli, John J., Zheng, Tongzhang, Birmann, Brenda M., Flowers, Christopher R., Becker, Nikolaus, Holly, Elizabeth A., Kane, Eleanor, Weisenburger, Dennis, Maynadie, Marc, Cocco, Pierluigi, Albanes, Demetrius, Weinstein, Stephanie J., Teras, Lauren R., Diver, W. Ryan, Lax, Stephanie J., Travis, Ruth C., Kaaks, Rudolf, Riboli, Elio, Benavente, Yolanda, Brennan, Paul, McKay, James D., Delfau-Larue, Marie Helene, Link, Brian K, Magnani, Corrado, Ennas, Maria G, Latte, Giancarlo, Feldman, Andrew L, Wong Doo, Nicole, Giles, Graham G., Southey, Melissa C., One Health Chemisch, and dIRAS RA-2

Abstract

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL=1.31, 95% CI=1.06-1.60; OR MZL=1.45, 95% CI=1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL=2.10, 95% CI=1.24-3.55; OR MZL= 2.10, 95% CI=0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (p-trend

Published
2018

372. Complex karyotype in mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy

Author

Greenwell, I Brian, Staton, Ashley D, Lee, Michael J, Switchenko, Jeffrey M, Saxe, Debra, Maly, Joseph J, Blum, Kristie A, Grover, Natalie S, Mathews, Stephanie, Gordon, Max J, Danilov, Alexey V, Epperla, Narendranath, Fenske, Timothy S, Hamadani, Mehdi, Park, Steven I, Flowers, Christopher R, and Cohen, Jonathon B

Subjects
Adult, Male, Karyotype, Lymphoma, Mantle-Cell, Risk Assessment, Transplantation, Autologous, Article, Predictive Value of Tests, Antineoplastic Combined Chemotherapy Protocols, Humans, Genetic Testing, Aged, Retrospective Studies, Aged, 80 and over, Chromosome Aberrations, Remission Induction, Hematopoietic Stem Cell Transplantation, Middle Aged, Prognosis, Combined Modality Therapy, Progression-Free Survival, United States, Ki-67 Antigen, Karyotyping, Female, Follow-Up Studies
Abstract

Risk stratification of newly diagnosed patients with mantle cell lymphoma (MCL) primarily is based on the MCL International Prognostic Index (MIPI) and Ki-67 proliferative index. Single-center studies have reported inferior outcomes in patients with a complex karyotype (CK), but this remains an area of controversy.The authors retrospectively reviewed 483 patients from 5 academic centers in the United States and described the effect of a CK on survival outcomes in individuals with MCL.A CK was found to be associated with inferior overall survival (OS) (4.5 vs 11.6 years; P.01) and progression-free survival (PFS) (1.9 vs 4.4 years; P.01). In patients who underwent high-intensity induction followed by autologous stem cell transplantation (ASCT) in first remission, a CK was associated with poor OS (5.1 vs 11.6 years; P = .04) and PFS (3.6 vs 7.8 years; P.01). Among patients with a CK, high-intensity induction had no effect on OS (4.5 vs 3.8 years; P = .77) nor PFS (2.3 vs 1.5 years; P = .46). Similarly, ASCT in first remission did not improve PFS (3.5 vs 1.2 years; P = .12) nor OS (5.1 vs 4.0 years; P = .27). On multivariable analyses with Ki-67 and MIPI, only CK was found to be predictive of OS (hazard ratio [HR], 1.98; 95% confidence interval [95% CI], 1.12-3.49 [P = .02]), whereas both CK (HR, 1.91; 95% CI, 1.17-3.12 [P = .01]) and Ki-6730% (HR, 1.86; 95% CI, 1.06-3.28 [P = .03]) were associated with inferior PFS. Multivariable analysis did not identify any specific cytogenetic abnormalities associated with inferior survival.CK appears to be independently associated with inferior outcomes in patients with MCL regardless of the intensity of induction therapy and receipt of ASCT. Cytogenetics should be incorporated into the workup of a new diagnosis of MCL and novel therapeutic approaches should be investigated for patients with CK. Cancer 2018;124:2306-15. © 2018 American Cancer Society.

Published
2018

373. Biologic, clinical, and sociodemographic predictors of multi-agent systemic therapy for non-Hodgkin lymphoma in people living with HIV: a population-based investigation in the state of Georgia

Author

Lipscomb, Joseph, primary, Switchenko, Jeffrey M., additional, Flowers, Christopher R., additional, Gillespie, Theresa W., additional, Wortley, Pascale M., additional, Bayakly, A. Rana, additional, Almon, Lyn, additional, Fernando, Robyn, additional, and Ward, Kevin C., additional

Published
2019
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374. Gemcitabine and bendamustine is a safe and effective salvage regimen for patients with recurrent/refractory Hodgkin lymphoma: Results of a phase 1/2 study

Author

Cohen, Jonathon B., primary, Wei, Lai, additional, Maddocks, Kami J., additional, Christian, Beth, additional, Heffner, Leonard T., additional, Langston, Amelia A., additional, Lechowicz, Mary Jo, additional, Porcu, Pierluigi, additional, Flowers, Christopher R., additional, Devine, Steven M., additional, and Blum, Kristie A., additional

Published
2019
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375. Polatuzumab Vedotin Plus Bendamustine with Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Updated Results of a Phase Ib/II Randomized Study

Author

Sehn, Laurie H, primary, Matasar, Matthew J, additional, Flowers, Christopher R., additional, Kamdar, Manali, additional, McMillan, Andrew K, additional, Hertzberg, Mark, additional, Assouline, Sarit, additional, Kim, Tae Min, additional, Kim, Won Seog, additional, Ozcan, Muhit, additional, Croft, Brandon, additional, Hirata, Jamie, additional, Cheng, Ji, additional, Ku, Grace, additional, and Herrera, Alex F., additional

Published
2019
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376. Maintenance Rituximab Improves Outcomes in Mantle Cell Lymphoma Patients Who Respond to Induction Therapy with Bendamustine + Rituximab without Autologous Transplant

Author

Hill, Brian T., primary, Switchenko, Jeffrey M., additional, Martin, Peter, additional, Churnetski, Michael C., additional, Sawalha, Yazeed, additional, Goyal, Subir, additional, Shanmugasundaram, Krithika, additional, Calzada, Oscar, additional, Kolla, Bhaskar, additional, Bachanova, Veronika, additional, Gerson, James N., additional, Barta, Stefan K., additional, Gordon, Max J., additional, Danilov, Alexey, additional, Grover, Natalie S, additional, Mathews, Stephanie, additional, Burkart, Madelyn, additional, Karmali, Reem, additional, Ghosh, Nilanjan, additional, Park, Steven I, additional, Epperla, Narendranath, additional, Bond, David A., additional, Badar, Talha, additional, Blum, Kristie A., additional, Guo, Jin, additional, Hamadani, Mehdi, additional, Fenske, Timothy S., additional, Malecek, Mary-Kate, additional, Kahl, Brad S., additional, Flowers, Christopher R., additional, and Cohen, Jonathon B., additional

Published
2019
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377. Short Time to Treatment Is Associated with Inferior Survival in Newly Diagnosed Patients with Mantle Cell Lymphoma

Author

Epperla, Narendranath, primary, Switchenko, Jeffrey M., additional, Shanmugasundaram, Krithika, additional, Goyal, Subir, additional, Calzada, Oscar, additional, Churnetski, Michael C., additional, Kolla, Bhaskar, additional, Bachanova, Veronika, additional, Gerson, James N., additional, Barta, Stefan K., additional, Gordon, Max J., additional, Danilov, Alexey, additional, Grover, Natalie S, additional, Mathews, Stephanie, additional, Burkart, Madelyn, additional, Karmali, Reem, additional, Sawalha, Yazeed, additional, Hill, Brian T., additional, Ghosh, Nilanjan, additional, Park, Steven I, additional, Bond, David A., additional, Badar, Talha, additional, Blum, Kristie A., additional, Hamadani, Mehdi, additional, Fenske, Timothy S., additional, Malecek, Mary-Kate, additional, Martin, Peter, additional, Guo, Jin, additional, Kahl, Brad S., additional, Flowers, Christopher R., additional, and Cohen, Jonathon B., additional

Published
2019
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378. Utility and Patterns of Use of PET/CT and Bone Marrow Biopsy for Staging in Non-Hodgkin Lymphoma in the Clinical Setting: A Retrospective Analysis Using the LEO Database

Author

Strouse, Christopher, primary, Rutherford, Sarah C., additional, Smith, Brian J, additional, Jaye, David L., additional, Kahl, Brad S., additional, Lossos, Izidore S., additional, Thompson, Carrie A., additional, Friedberg, Jonathan W., additional, Feldman, Andrew L., additional, Casulo, Carla, additional, Cohen, Jonathon B., additional, Chapman, Jennifer R, additional, Syrbu, Sergei, additional, Witzig, Thomas E., additional, Nastoupil, Loretta J., additional, McDonnell, Timothy J., additional, Larson, Melissa C, additional, Habermann, Thomas M., additional, Slager, Susan L., additional, Flowers, Christopher R., additional, Cerhan, James R., additional, Martin, Peter, additional, and Link, Brian K., additional

Published
2019
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380. The Impact of Pre-Diagnosis Tobacco Use in Mantle Cell Lymphoma

Author

Romancik, Jason, primary, Switchenko, Jeffrey M., additional, Shanmugasundaram, Krithika, additional, Goyal, Subir, additional, Calzada, Oscar, additional, Churnetski, Michael C., additional, Kolla, Bhaskar, additional, Bachanova, Veronika, additional, Gerson, James N., additional, Barta, Stefan K., additional, Gordon, Max J., additional, Danilov, Alexey, additional, Grover, Natalie S, additional, Mathews, Stephanie, additional, Burkhart, Madelyn, additional, Karmali, Reem, additional, Sawalha, Yazeed, additional, Hill, Brian T., additional, Ghosh, Nilanjan, additional, Park, Steven I, additional, Epperla, Narendranath, additional, Bond, David A., additional, Badar, Talha, additional, Blum, Kristie A., additional, Hamadani, Mehdi, additional, Fenske, Timothy S., additional, Malecek, Mary-Kate, additional, Kahl, Brad S., additional, Martin, Peter, additional, Guo, Jin, additional, Flowers, Christopher R., additional, and Cohen, Jonathon B., additional

Published
2019
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381. Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma

Author

Li, Xiang, primary, Kositsky, Rachel, primary, Reddy, Anupama, primary, Love, Cassandra, primary, Naresh, Kikkeri, primary, Koff, Jean L., primary, Nystrand, Ilja, primary, Leppä, Sirpa, primary, Pasanen, Annika, primary, Karjalainen-Lindsberg, Marja-Liisa, primary, Dunkel, Johannes, primary, Kovanen, Panu, primary, Qin, Qiu, primary, Bhagat, Govind, primary, Leeman-Neill, Rebecca J, primary, Goswami, Rashmi S., primary, Wildeman, Sarah, primary, Delabie, Jan, primary, Burack, Richard, primary, Evans, Andrew G, primary, Amador, Catalina, primary, Yuan, Ji, primary, Qureishi, Hina Naushad, primary, Li, Shaoying, primary, Xu, Jie, primary, Yin, C. Cameron, primary, Gang, Anne Ortved, primary, Norgaard, Peter H., primary, Pedersen, Mette Ø, primary, Chan, Jason Yongsheng, primary, Cheah, Daryl Ming Zhe, primary, Ong, Shin Yeu, primary, Cheng, Chee Leong, primary, Lee, Lianne, primary, Paulua, Felik, primary, Ondrejka, Sarah L., primary, Hsi, Eric D., primary, Czader, Magdalena, primary, Wang, Lin, primary, Landis, Amber, primary, Churnetski, Michael C., primary, Jaye, David L., primary, Flowers, Christopher R., primary, McCall, Chad M., primary, Neff, Jadee, primary, McKinney, Matthew S., primary, Fedoriw, Yuri, primary, Powers, Eric, primary, Montgomery, Nathan D, primary, Bogusz, Agata M., primary, Stafford Hintz, Andrea, primary, Kovach, Alexandra E., primary, Reddy, Nishitha, primary, Thompson Arildsen, Mary Ann, primary, Mason, Emily F, primary, Juskevicius, Ridas, primary, Choi, William, primary, Au-Yeung, Rex, primary, Tse, Eric, primary, Sarno, Vincent, primary, Chadburn, Amy, primary, Lopez, Rafael, primary, Chapman, Jennifer R, primary, Behdad, Amir, primary, Goldschmidt, Neta, primary, Goodlad, John, primary, Burton, Cathy, primary, Pillai, Raju, primary, Louissaint, Abner, primary, Soliman, Dina Sameh, primary, Panea, Razvan, primary, Dave, Tushar, primary, Xiong, Barbara, primary, Smith, Eileen, primary, and Dave, Sandeep, primary

Published
2019
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385. Outcomes Following Early Relapse in Patients with Mantle Cell Lymphoma

Author

Bond, David A., primary, Switchenko, Jeffrey M., primary, Maddocks, Kami J., primary, Churnetski, Michael C., primary, Goyal, Subir, primary, Shanmugasundaram, Krithika, primary, Calzada, Oscar, primary, Kolla, Bhaskar, primary, Bachanova, Veronika, primary, Gerson, James N., primary, Barta, Stefan K., primary, Sawalha, Yazeed, primary, Hill, Brian T., primary, Martin, Peter, primary, Gordon, Max J., primary, Danilov, Alexey, primary, Grover, Natalie S, primary, Mathews, Stephanie, primary, Burkart, Madelyn, primary, Karmali, Reem, primary, Ghosh, Nilanjan, primary, Park, Steven I, primary, Epperla, Narendranath, primary, Badar, Talha, primary, Guo, Jin, primary, Hamadani, Mehdi, primary, Fenske, Timothy S., primary, Malecek, Mary-Kate, primary, Kahl, Brad S., primary, Flowers, Christopher R., primary, Blum, Kristie A., primary, and Cohen, Jonathon B., primary

Published
2019
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387. Vulnerable Elders Survey-13 (VES-13) Predicts 1-Year Mortality Risk in Newly Diagnosed Non-Hodgkin Lymphoma (NHL)

Author

Fama, Angelo, primary, Martin, Peter, primary, Allmer, Cristine, primary, Casulo, Carla, primary, Cohen, Jonathon B., primary, Farooq, Umar, primary, Feldman, Andrew L., primary, Friedberg, Jonathan W., primary, Habermann, Thomas M., primary, Jaye, David L., primary, Kahl, Brad S., primary, Link, Brian K., primary, Lossos, Izidore S., primary, Maurer, Matthew J., primary, Nastoupil, Loretta J., primary, Rutherford, Sarah C., primary, Slager, Susan L, primary, Thompson, Carrie A., primary, Flowers, Christopher R., primary, and Cerhan, James R., primary

Published
2019
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388. Age and Time to Progression Predict Overall Survival (OS) in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Who Progress Following Frontline Immunochemotherapy (IC)

Author

Maurer, Matthew J., primary, Jakobsen, Lasse H., primary, Schmitz, Norbert, primary, Farooq, Umar, primary, Flowers, Christopher R., primary, Brown, Peter de Nully, primary, Thompson, Carrie A., primary, Frederiksen, Henrik, primary, Cunningham, David, primary, Jørgensen, Judit, primary, Poeschel, Viola, primary, Nowakowski, Grzegorz, primary, Seymour, John F., primary, Merli, Francesco, primary, Haioun, Corinne, primary, Ghesquieres, Herve, primary, Ziepert, Marita, primary, Tilly, Herve, primary, Salles, Gilles, primary, Shi, Qian, primary, El-Galaly, Tarec Christoffer C., primary, and Habermann, Thomas M., primary

Published
2019
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389. Clinical Trial Participation Is Associated with Improved Overall Survival in Newly Diagnosed Patients with Mantle Cell Lymphoma

Author

Cohen, Jonathon B., primary, Switchenko, Jeffrey M., additional, Shanmugasundaram, Krithika, additional, Goyal, Subir, additional, Calzada, Oscar, additional, Churnetski, Michael C., additional, Kolla, Bhaskar, additional, Bachanova, Veronika, additional, Gerson, James N., additional, Barta, Stefan K., additional, Gordon, Max J., additional, Danilov, Alexey, additional, Grover, Natalie S, additional, Mathews, Stephanie, additional, Burkart, Madelyn, additional, Karmali, Reem, additional, Sawalha, Yazeed, additional, Hill, Brian T., additional, Ghosh, Nilanjan, additional, Park, Steven I, additional, Epperla, Narendranath, additional, Bond, David A., additional, Badar, Talha, additional, Blum, Kristie A., additional, Hamadani, Mehdi, additional, Fenske, Timothy S., additional, Malecek, Mary-Kate, additional, Martin, Peter, additional, Guo, Jin, additional, Flowers, Christopher R., additional, and Kahl, Brad S., additional

Published
2019
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390. Indolent Lymphoma and Vitamin D (ILyAD): A Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Supplemental Effect of Vitamin D on Event-Free Survival in Patients with Low Tumor Burden Indolent Non-Hodgkin Lymphoma Treated with Rituximab

Author

Friedberg, Jonathan W., primary, Brady, Michael T., additional, Strawderman, Myla, additional, Kahl, Brad S., additional, Leonard, John P., additional, Lossos, Izidore S., additional, Flowers, Christopher R., additional, Sutamtewagul, Grerk, additional, Cohen, Jonathon B., additional, Peterson, Derick R., additional, and Nastoupil, Loretta J., additional

Published
2019
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391. A Multistate Survival Analysis for Patients with Follicular Lymphoma (FL) Using 13 First-Line Randomized Trials from FL Analysis of Surrogate Hypothesis (FLASH) Group

Author

Caglayan, Caglar, primary, Dixon, Jesse, additional, Wall, Anna, additional, Salles, Gilles A., additional, Hoster, Eva, additional, Hiddemann, Wolfgang, additional, Herold, Michael, additional, Morschhauser, Franck, additional, Sebban, Catherine, additional, Hagenbeek, Anton, additional, Marcus, Robert, additional, Hochster, Howard, additional, Rummel, Mathias J, additional, Kimby, Eva, additional, Vitolo, Umberto, additional, Peterson, Bruce A., additional, Gyan, Emmanuel, additional, Ladetto, Marco, additional, Foussard, Charles Yves, additional, Ghielmini, Michele, additional, Nielsen, Tina G, additional, Foon, Kenneth, additional, Shi, Qian, additional, and Flowers, Christopher R., additional

Published
2019
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396. The whole-genome landscape of Burkitt lymphoma subtypes

Author

Panea, Razvan I., primary, Love, Cassandra L., additional, Shingleton, Jennifer R., additional, Reddy, Anupama, additional, Bailey, Jeffrey A., additional, Moormann, Ann M., additional, Otieno, Juliana A., additional, Ong’echa, John Michael, additional, Oduor, Cliff I., additional, Schroeder, Kristin M. S., additional, Masalu, Nestory, additional, Chao, Nelson J., additional, Agajanian, Megan, additional, Major, Michael B., additional, Fedoriw, Yuri, additional, Richards, Kristy L., additional, Rymkiewicz, Grzegorz, additional, Miles, Rodney R., additional, Alobeid, Bachir, additional, Bhagat, Govind, additional, Flowers, Christopher R., additional, Ondrejka, Sarah L., additional, Hsi, Eric D., additional, Choi, William W. L., additional, Au-Yeung, Rex K. H., additional, Hartmann, Wolfgang, additional, Lenz, Georg, additional, Meyerson, Howard, additional, Lin, Yen-Yu, additional, Zhuang, Yuan, additional, Luftig, Micah A., additional, Waldrop, Alexander, additional, Dave, Tushar, additional, Thakkar, Devang, additional, Sahay, Harshit, additional, Li, Guojie, additional, Palus, Brooke C., additional, Seshadri, Vidya, additional, Kim, So Young, additional, Gascoyne, Randy D., additional, Levy, Shawn, additional, Mukhopadyay, Minerva, additional, Dunson, David B., additional, and Dave, Sandeep S., additional

Published
2019
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397. Ublituximab and umbralisib in relapsed/refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia

Author

Lunning, Matthew, primary, Vose, Julie, additional, Nastoupil, Loretta, additional, Fowler, Nathan, additional, Burger, Jan A., additional, Wierda, William G., additional, Schreeder, Marshall T., additional, Siddiqi, Tanya, additional, Flowers, Christopher R., additional, Cohen, Jonathon B., additional, Sportelli, Peter, additional, Miskin, Hari P., additional, Weiss, Michael S., additional, and O’Brien, Susan, additional

Published
2019
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