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720 results on '"Zelenetz, Andrew"'

1. Limited stage high grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements: BCL2 rearrangements drives the poor outcomes

Author

Lue, Jennifer K., Luttwak, Efrat, Rivas-Delgado, Alfredo, Irawan, Helen, Boardman, Alexander, Caron, Philip C., David, Kevin, Epstein-Peterson, Zachary, Falchi, Lorenzo, Ghione, Paola, Hamlin, Paul, Horwitz, Steven M., Intlekofer, Andrew M., Johnson, William, Kumar, Anita, Moskowitz, Alison, Noy, Ariela, Palomba, M. Lia, Steiner, Ralphael, Stuver, Robert, Torka, Pallawi, Vardhana, Santosha, Zelenetz, Andrew D., Schoder, Heiko, Imber, Brandon, Yahalom, Joachim, Zhang, Yanming, Galera, Pallavi, Dogan, Ahmet, Aypar, Umut, and Salles, Gilles

Published
2024
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3. Matched control analysis suggests that R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared with R-CHOP

Author

Bantilan, Kurt S., Smith, Alexandra N., Maurer, Matthew J., Teruya-Feldstein, Julie, Matasar, Matthew J., Moskowitz, Alison J., Straus, David J., Noy, Ariela, Palomba, M. Lia, Horwitz, Steven M., Hamlin, Paul A., Portlock, Carol S., Cerhan, James R., Habermann, Thomas M., Salles, Gilles A., Nowakowski, Grzegorz S., Moskowitz, Craig H., and Zelenetz, Andrew D.

Published
2024
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4. Mechanisms of Resistance to Noncovalent Brutons Tyrosine Kinase Inhibitors.

Author

Wang, Eric, Mi, Xiaoli, Thompson, Meghan, Montoya, Skye, Notti, Ryan, Afaghani, Jumana, Durham, Benjamin, Penson, Alex, Witkowski, Matthew, Lu, Sydney, Bourcier, Jessie, Hogg, Simon, Erickson, Caroline, Cui, Dan, Cho, Hana, Singer, Michael, Totiger, Tulasigeri, Chaudhry, Sana, Geyer, Mark, Alencar, Alvaro, Linley, Adam, Palomba, M, Coombs, Catherine, Park, Jae, Zelenetz, Andrew, Roeker, Lindsey, Rosendahl, Mary, Tsai, Donald, Ebata, Kevin, Brandhuber, Barbara, Hyman, David, Aifantis, Iannis, Mato, Anthony, Taylor, Justin, and Abdel-Wahab, Omar

Subjects
Humans, Middle Aged, Adenine, Agammaglobulinaemia Tyrosine Kinase, Drug Resistance, Neoplasm, Leukemia, Lymphocytic, Chronic, B-Cell, Mutation, Phospholipase C gamma, Piperidines, Protein Kinase Inhibitors, Receptors, Antigen, B-Cell, Sequence Analysis, RNA, Signal Transduction
Abstract

BACKGROUND: Covalent (irreversible) Brutons tyrosine kinase (BTK) inhibitors have transformed the treatment of multiple B-cell cancers, especially chronic lymphocytic leukemia (CLL). However, resistance can arise through multiple mechanisms, including acquired mutations in BTK at residue C481, the binding site of covalent BTK inhibitors. Noncovalent (reversible) BTK inhibitors overcome this mechanism and other sources of resistance, but the mechanisms of resistance to these therapies are currently not well understood. METHODS: We performed genomic analyses of pretreatment specimens as well as specimens obtained at the time of disease progression from patients with CLL who had been treated with the noncovalent BTK inhibitor pirtobrutinib. Structural modeling, BTK-binding assays, and cell-based assays were conducted to study mutations that confer resistance to noncovalent BTK inhibitors. RESULTS: Among 55 treated patients, we identified 9 patients with relapsed or refractory CLL and acquired mechanisms of genetic resistance to pirtobrutinib. We found mutations (V416L, A428D, M437R, T474I, and L528W) that were clustered in the kinase domain of BTK and that conferred resistance to both noncovalent BTK inhibitors and certain covalent BTK inhibitors. Mutations in BTK or phospholipase C gamma 2 (PLCγ2), a signaling molecule and downstream substrate of BTK, were found in all 9 patients. Transcriptional activation reflecting B-cell-receptor signaling persisted despite continued therapy with noncovalent BTK inhibitors. CONCLUSIONS: Resistance to noncovalent BTK inhibitors arose through on-target BTK mutations and downstream PLCγ2 mutations that allowed escape from BTK inhibition. A proportion of these mutations also conferred resistance across clinically approved covalent BTK inhibitors. These data suggested new mechanisms of genomic escape from established covalent and novel noncovalent BTK inhibitors. (Funded by the American Society of Hematology and others.).

Published
2022

5. Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation

Author

Kumar, Anita, Soumerai, Jacob, Abramson, Jeremy S., Barnes, Jeffrey A., Caron, Philip, Chhabra, Shalini, Chabowska, Maria, Dogan, Ahmet, Falchi, Lorenzo, Grieve, Clare, Haydu, J. Erika, Johnson, Patrick Connor, Joseph, Ashlee, Kelly, Hailey E., Labarre, Alyssa, Lue, Jennifer Kimberly, Martignetti, Rosalba, Mi, Joanna, Moskowitz, Alison, Owens, Colette, Plummer, Sean, Puccio, Madeline, Salles, Gilles, Seshan, Venkatraman, Simkins, Elizabeth, Slupe, Natalie, Zhang, Honglei, and Zelenetz, Andrew D.

Published
2024
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6. Retrospective characterization of nodal marginal zone lymphoma

Author

Stuver, Robert, Drill, Esther, Qualls, David, Okwali, Michelle, Lee Batlevi, Connie, Caron, Philip C., Dogan, Ahmet, Epstein-Peterson, Zachary D., Falchi, Lorenzo, Hamlin, Paul A., Horwitz, Steven M., Imber, Brandon S., Intlekofer, Andrew M., Johnson, William T., Khan, Niloufer, Kumar, Anita, Lahoud, Oscar B., Lue, Jennifer Kimberly, Matasar, Matthew J., Moskowitz, Alison J., Noy, Ariela, Owens, Colette N., Palomba, M. Lia, Schöder, Heiko, Vardhana, Santosha A., Yahalom, Joachim, Zelenetz, Andrew D., Salles, Gilles, and Straus, David J.

Published
2023
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7. TP53 mutations identify high-risk events for peripheral T-cell lymphoma treated with CHOP-based chemotherapy

Author

Johnson, William T., Ganesan, Nivetha, Epstein-Peterson, Zachary D., Moskowitz, Alison J., Stuver, Robert N., Maccaro, Catherine R., Galasso, Natasha, Chang, Tiffany, Khan, Niloufer, Aypar, Umut, Lewis, Natasha E., Zelenetz, Andrew D., Palomba, M. Lia, Matasar, Matthew J., Noy, Ariela, Hamilton, Audrey M., Hamlin, Paul, Caron, Philip C., Straus, David J., Intlekofer, Andrew M., Lee Batlevi, Connie, Kumar, Anita, Owens, Colette N., Sauter, Craig S., Falchi, Lorenzo, Lue, Jennifer K., Vardhana, Santosha A., Salles, Gilles, Dogan, Ahmet, Schultz, Nikolaus D., Arcila, Maria E., and Horwitz, Steven M.

Published
2023
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8. Risk factors for grade 3/4 transaminase elevation in patients with chronic lymphocytic leukemia treated with idelalisib

Author

Brown, Jennifer R, Zelenetz, Andrew, Furman, Richard, Lamanna, Nicole, Mato, Anthony, Montillo, Marco, O’Brien, Susan, Dubowy, Ronald, Gu, Lin, Munugalavadla, Veerendra, Robak, Tadeusz, and Hillmen, Peter

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Antineoplastic Agents, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Purines, Quinazolinones, Risk Factors, Transaminases, Clinical Sciences, Immunology, Cardiovascular medicine and haematology, Clinical sciences, Oncology and carcinogenesis
Published
2020

9. Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents.

Author

Roeker, Lindsey, Dreger, Peter, Brown, Jennifer, Lahoud, Oscar, Eyre, Toby, Brander, Danielle, Skarbnik, Alan, Coombs, Catherine, Kim, Haesook, Davids, Matthew, Manchini, Steven, George, Gemlyn, Shah, Nirav, Voorhees, Timothy, Orchard, Kim, Walter, Harriet, Arumainathan, Arvind, Sitlinger, Andrea, Park, Jae, Geyer, Mark, Zelenetz, Andrew, Sauter, Craig, Giralt, Sergio, Perales, Miguel-Angel, and Mato, Anthony

Subjects
Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Retrospective Studies
Abstract

Although novel agents (NAs) have improved outcomes for patients with chronic lymphocytic leukemia (CLL), a subset will progress through all available NAs. Understanding outcomes for potentially curative modalities including allogeneic hematopoietic stem cell transplantation (alloHCT) following NA therapy is critical while devising treatment sequences aimed at long-term disease control. In this multicenter, retrospective cohort study, we examined 65 patients with CLL who underwent alloHCT following exposure to ≥1 NA, including baseline disease and transplant characteristics, treatment preceding alloHCT, transplant outcomes, treatment following alloHCT, and survival outcomes. Univariable and multivariable analyses evaluated associations between pre-alloHCT factors and progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS), nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in 27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial remission, and transplant characteristics were not independently associated with PFS. Hematopoietic cell transplantation-specific comorbidity index independently predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease control strategy that overcomes adverse CLL characteristics. Prior NAs do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA immediately preceding alloHCT. Decisions about proceeding to alloHCT should consider comorbidities and anticipated response to remaining therapeutic options.

Published
2020

10. Assessment of the Efficacy of Therapies Following Venetoclax Discontinuation in CLL Reveals BTK Inhibition as an Effective Strategy.

Author

Mato, Anthony R, Roeker, Lindsey E, Jacobs, Ryan, Hill, Brian T, Lamanna, Nicole, Brander, Danielle, Shadman, Mazyar, Ujjani, Chaitra S, Yazdy, Maryam Sarraf, Perini, Guilherme Fleury, Pinilla-Ibarz, Javier A, Barrientos, Jacqueline, Skarbnik, Alan P, Torka, Pallawi, Pu, Jeffrey J, Pagel, John M, Gohil, Satyen, Fakhri, Bita, Choi, Michael, Coombs, Catherine C, Rhodes, Joanna, Barr, Paul M, Portell, Craig A, Parry, Helen, Garcia, Christine A, Whitaker, Kate J, Winter, Allison M, Sitlinger, Andrea, Khajavian, Sirin, Grajales-Cruz, Ariel F, Isaac, Krista M, Shah, Pratik, Akhtar, Othman S, Pocock, Rachael, Lam, Kentson, Voorhees, Timothy J, Schuster, Stephen J, Rodgers, Thomas D, Fox, Christopher P, Martinez-Calle, Nicolas, Munir, Talha, Bhavsar, Erica B, Bailey, Neil, Lee, Jason C, Weissbrot, Hanna B, Nabhan, Chadi, Goodfriend, Julie M, King, Amber C, Zelenetz, Andrew D, Dorsey, Colleen, Bigelow, Kayla, Cheson, Bruce D, Allan, John N, and Eyre, Toby A

Subjects
Humans, Sulfonamides, Pyrazoles, Pyrimidines, Protein Kinase Inhibitors, Leukemia, Lymphocytic, Chronic, B-Cell, Phosphatidylinositol 3-Kinases, Bridged Bicyclo Compounds, Heterocyclic, Rare Diseases, Cancer, Clinical Research, Hematology, Good Health and Well Being, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeVenetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood.Experimental designTo address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Coprimary endpoints were overall response rate (ORR) and progression-free survival for the post-venetoclax treatments stratified by treatment type [Bruton's tyrosine kinase inhibitor (BTKi), PI3K inhibitor (PI3Ki), and cellular therapies].ResultsWe identified patients with CLL who discontinued venetoclax in the first-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve (n = 130), and 81% were idelalisib naïve (n = 263). ORR to BTKi was 84% (n = 44) in BTKi-naïve patients versus 54% (n = 30) in BTKi-exposed patients. We demonstrate therapy selection following venetoclax requires prior novel agent exposure consideration and discontinuation reasons.ConclusionsFor BTKi-naïve patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi-exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.See related commentary by Rogers, p. 3501.

Published
2020

11. Final Results of a Randomized, Phase III Study of Rituximab With or Without Idelalisib Followed by Open-Label Idelalisib in Patients With Relapsed Chronic Lymphocytic Leukemia.

Author

Sharman, Jeff, Coutre, Steven, Furman, Richard, Cheson, Bruce, Pagel, John, Hillmen, Peter, Barrientos, Jacqueline, Zelenetz, Andrew, Flinn, Ian, Ghia, Paolo, Eradat, Herbert, Ervin, Thomas, Lamanna, Nicole, Coiffier, Bertrand, Pettitt, Andrew, Ma, Shuo, Tausch, Eugen, Cramer, Paula, Huang, Julie, Mitra, Siddhartha, Hallek, Michael, Stilgenbauer, Stephan, OBrien, Susan, and Kipps, Thomas

Subjects
Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Double-Blind Method, Drug Administration Schedule, Europe, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Progression-Free Survival, Purines, Quinazolinones, Recurrence, Rituximab, Time Factors, United States
Abstract

PURPOSE: A randomized, double-blind, phase III study of idelalisib (IDELA) plus rituximab versus placebo plus rituximab in patients with relapsed chronic lymphocytic leukemia (CLL) was terminated early because of superior efficacy of the IDELA-plus-rituximab (IDELA/R) arm. Patients in either arm could then enroll in an extension study to receive IDELA monotherapy. Here, we report the long-term efficacy and safety data for IDELA-treated patients across the primary and extension studies. PATIENTS AND METHODS: Patients were randomly assigned to receive rituximab in combination with either IDELA 150 mg twice daily (IDELA/R; n = 110) or placebo (placebo/R; n = 110). Key end points were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety. RESULTS: The long-term efficacy and safety of treatment with IDELA was assessed in 110 patients who received at least one dose of IDELA in the primary study, 75 of whom enrolled in the extension study. The IDELA/R-to-IDELA group had a median PFS of 20.3 months (95% CI, 17.3 to 26.3 months) after a median follow-up time of 18 months (range, 0.3 to 67.6 months). The ORR was 85.5% (94 of 110 patients; n = 1 complete response). The median OS was 40.6 months (95% CI, 28.5 to 57.3 months) and 34.6 months (95% CI, 16.0 months to not reached) for patients randomly assigned to the IDELA/R and placebo/R groups, respectively. Prolonged exposure to IDELA increased the incidence of all-grade, grade 2, and grade 3 or greater diarrhea (46.4%, 17.3%, and 16.4%, respectively), all-grade and grade 3 or greater colitis (10.9% and 8.2%, respectively) and all-grade and grade 3 or greater pneumonitis (10.0% and 6.4%, respectively) but did not increase the incidence of elevated hepatic aminotransferases. CONCLUSION: IDELA improved PFS and OS compared with rituximab alone in patients with relapsed CLL. Long-term IDELA was effective and had an expected safety profile. No new IDELA-related adverse events were identified with longer exposure.

Published
2019

12. A retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R/R CLL.

Author

Mato, Anthony, Roeker, Lindsey, Eyre, Toby, Nabhan, Chadi, Lamanna, Nicole, Hill, Brian, Brander, Danielle, Barr, Paul, Lansigan, Frederick, Cheson, Bruce, Singavi, Arun, Yazdy, Maryam, Shah, Nirav, Allan, John, Bhavsar, Erica, Rhodes, Joanna, Kennard, Kaitlin, Schuster, Stephen, Williams, AnnaLynn, Skarbnik, Alan, Goy, Andre, Goodfriend, Julie, Dorsey, Colleen, Coombs, Catherine, Tuncer, Hande, Ujjani, Chaitra, Jacobs, Ryan, Winter, Allison, Pagel, John, Bailey, Neil, Schuh, Anna, Shadman, Mazyar, Sitlinger, Andrea, Weissbrot, Hanna, Muralikrishnan, Sivraj, Zelenetz, Andrew, Kirkwood, Amy, and Fox, Christopher

Subjects
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Bridged Bicyclo Compounds, Heterocyclic, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Progression-Free Survival, Retrospective Studies, Sulfonamides
Abstract

Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings.

Published
2019

13. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee

Author

Campo, Elias, Jaffe, Elaine S., Cook, James R., Quintanilla-Martinez, Leticia, Swerdlow, Steven H., Anderson, Kenneth C., Brousset, Pierre, Cerroni, Lorenzo, de Leval, Laurence, Dirnhofer, Stefan, Dogan, Ahmet, Feldman, Andrew L., Fend, Falko, Friedberg, Jonathan W., Gaulard, Philippe, Ghia, Paolo, Horwitz, Steven M., King, Rebecca L., Salles, Gilles, San-Miguel, Jesus, Seymour, John F., Treon, Steven P., Vose, Julie M., Zucca, Emanuele, Advani, Ranjana, Ansell, Stephen, Au, Wing-Yan, Barrionuevo, Carlos, Bergsagel, Leif, Chan, Wing C., Cohen, Jeffrey I., d'Amore, Francesco, Davies, Andrew, Falini, Brunangelo, Ghobrial, Irene M., Goodlad, John R., Gribben, John G., Hsi, Eric D., Kahl, Brad S., Kim, Won-Seog, Kumar, Shaji, LaCasce, Ann S., Laurent, Camille, Lenz, Georg, Leonard, John P., Link, Michael P., Lopez-Guillermo, Armando, Mateos, Maria Victoria, Macintyre, Elizabeth, Melnick, Ari M., Morschhauser, Franck, Nakamura, Shigeo, Narbaitz, Marina, Pavlovsky, Astrid, Pileri, Stefano A., Piris, Miguel, Pro, Barbara, Rajkumar, Vincent, Rosen, Steven T., Sander, Birgitta, Sehn, Laurie, Shipp, Margaret A., Smith, Sonali M., Staudt, Louis M., Thieblemont, Catherine, Tousseyn, Thomas, Wilson, Wyndham H., Yoshino, Tadashi, Zinzani, Pier-Luigi, Dreyling, Martin, Scott, David W., Winter, Jane N., and Zelenetz, Andrew D.

Published
2022
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14. Zandelisib with continuous or intermittent dosing as monotherapy or in combination with rituximab in patients with relapsed or refractory B-cell malignancy: a multicentre, first-in-patient, dose-escalation and dose-expansion, phase 1b trial

Author

Pagel, John M, Soumerai, Jacob D, Reddy, Nishitha, Jagadeesh, Deepa, Stathis, Anastasios, Asch, Adam, Salman, Huda, Kenkre, Vaishalee P, Iasonos, Alexia, Llorin-Sangalang, Judith, Li, Joanne, and Zelenetz, Andrew D

Published
2022
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15. Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial

Author

Soumerai, Jacob D, Mato, Anthony R, Dogan, Ahmet, Seshan, Venkatraman E, Joffe, Erel, Flaherty, Kelsey, Carter, Jason, Hochberg, Ephraim, Barnes, Jeffrey A, Hamilton, Audrey M, Abramson, Jeremy S, Batlevi, Connie L, Matasar, Matthew J, Noy, Ariela, Owens, Colette N, Palomba, M Lia, Kumar, Anita, Takvorian, Tak, Ni, Ai, Choma, Morgan, Friedman, Chaya, Chadha, Puja, Simkins, Elizabeth, Ruiters, Jade, Sechio, Sidney, Portman, Daneal, Ramos, Lauren, Nolet, Natascha, Mahajan, Neena, Martignetti, Rosalba, Mi, Joanna, Scorsune, Krista, Lynch, Julia, McGree, Brianne, Hughes, Stephanie, Grieve, Clare, Roeker, Lindsey E, Thompson, Meghan, Johnson, P Connor, Roshal, Mikhail, Huang, Jane, Biondo, Juliana, Wu, Qun, Jacob, Allison, Abdel-Wahab, Omar, and Zelenetz, Andrew D

Published
2021
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17. Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter's transformation

Author

Lahoud, Oscar B., Devlin, Sean M., Maloy, Molly A., Roeker, Lindsey E., Dahi, Parastoo B., Ponce, Doris M., Gyurkocza, Boglarka, Koehne, Guenther, Young, James W., Castro-Malaspina, Hugo R., Barker, Juliet N., Papadopoulos, Esperanza B., Jakubowski, Ann A., Zelenetz, Andrew D., Mato, Anthony R., Giralt, Sergio A., Perales, Miguel A., and Sauter, Craig S.

Published
2021
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19. A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma

Author

Morschhauser, Franck, Feugier, Pierre, Flinn, Ian W., Gasiorowski, Robin, Greil, Richard, Illés, Árpád, Johnson, Nathalie A., Larouche, Jean-François, Lugtenburg, Pieternella J., Patti, Caterina, Salles, Gilles A., Trněný, Marek, de Vos, Sven, Mir, Farheen, Samineni, Divya, Kim, Su Y., Jiang, Yanwen, Punnoose, Elizabeth, Sinha, Arijit, Clark, Emma, Spielewoy, Nathalie, Humphrey, Kathryn, Bazeos, Alexandra, and Zelenetz, Andrew D.

Published
2021
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21. Clinical characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma in the rituximab era

Author

Bobillo, Sabela, Joffe, Erel, Lavery, Jessica A., Sermer, David, Ghione, Paola, Noy, Ariela, Caron, Philip C., Hamilton, Audrey, Hamlin, Paul A., Horwitz, Steven M., Kumar, Anita, Matasar, Matthew J., Moskowitz, Alison, Owens, Collette N., Palomba, M. Lia, Batlevi, Connie L., Straus, David, von Keudell, Gottfried, Zelenetz, Andrew D., Yahalom, Joachim, Dogan, Ahmet, Seshan, Venkatraman E., and Younes, Anas

Published
2021
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23. The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study.

Author

Zelenetz, Andrew D., Jurczak, Wojciech, Ribrag, Vincent, Linton, Kim, Collins, Graham P., Jiménez, Javier L., Bishton, Mark, Dholaria, Bhagirathbhai, Mengarelli, Andrea, Phillips, Tycel J., Sungala, Nagendraprasad, Musuraca, Gerardo, Sheehy, Oonagh, Van Den Neste, Eric, Odera, Mitsuhiko, Miao, Lu, Gold, Daniel P., Ghalie, Richard G., and Zinzani, Pier L.

Published
2024
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24. Outcomes in patients with DLBCL treated with commercial CAR T cells compared with alternate therapies

Author

Sermer, David, Batlevi, Connie, Palomba, M. Lia, Shah, Gunjan, Lin, Richard J., Perales, Miguel-Angel, Scordo, Michael, Dahi, Parastoo, Pennisi, Martina, Afuye, Aishat, Silverberg, Mari Lynne, Ho, Caleb, Flynn, Jessica, Devlin, Sean, Caron, Philip, Hamilton, Audrey, Hamlin, Paul, Horwitz, Steven, Joffe, Erel, Kumar, Anita, Matasar, Matthew, Noy, Ariela, Owens, Colette, Moskowitz, Alison, Straus, David, von Keudell, Gottfried, Rodriguez-Rivera, Ildefonso, Falchi, Lorenzo, Zelenetz, Andrew, Yahalom, Joachim, Younes, Anas, and Sauter, Craig

Published
2020
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25. Extra copies of MYC, BCL2, and BCL6 and outcome in patients with diffuse large B-cell lymphoma

Author

Sermer, David, Bobillo, Sabela, Dogan, Ahmet, Zhang, Yanming, Seshan, Venkatraman, Lavery, Jessica A., Batlevi, Connie, Caron, Philip, Hamilton, Audrey, Hamlin, Paul, Horwitz, Steven, Joffe, Erel, Kumar, Anita, Matasar, Matthew, Noy, Ariela, Owens, Colette, Moskowitz, Alison, Palomba, M. Lia, Straus, David, von Keudell, Gottfried, Rodriguez-Rivera, Ildefonso, Falchi, Lorenzo, Zelenetz, Andrew, Yahalom, Joachim, and Younes, Anas

Published
2020
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26. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Author

Machiela, Mitchell J, Lan, Qing, Slager, Susan L, Vermeulen, Roel CH, Teras, Lauren R, Camp, Nicola J, Cerhan, James R, Spinelli, John J, Wang, Sophia S, Nieters, Alexandra, Vijai, Joseph, Yeager, Meredith, Wang, Zhaoming, Ghesquières, Hervé, McKay, James, Conde, Lucia, de Bakker, Paul IW, Cox, David G, Burdett, Laurie, Monnereau, Alain, Flowers, Christopher R, De Roos, Anneclaire J, Brooks-Wilson, Angela R, Giles, Graham G, Melbye, Mads, Gu, Jian, Jackson, Rebecca D, Kane, Eleanor, Purdue, Mark P, Vajdic, Claire M, Albanes, Demetrius, Kelly, Rachel S, Zucca, Mariagrazia, Bertrand, Kimberly A, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Hutchinson, Amy, Zhi, Degui, Habermann, Thomas M, Link, Brian K, Novak, Anne J, Dogan, Ahmet, Asmann, Yan W, Liebow, Mark, Thompson, Carrie A, Ansell, Stephen M, Witzig, Thomas E, Tilly, Hervé, Haioun, Corinne, Molina, Thierry J, Hjalgrim, Henrik, Glimelius, Bengt, Adami, Hans-Olov, Roos, Göran, Bracci, Paige M, Riby, Jacques, Smith, Martyn T, Holly, Elizabeth A, Cozen, Wendy, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Tinker, Lesley F, North, Kari E, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, Lightfoot, Tracy, Crouch, Simon, Smith, Alex, Roman, Eve, Diver, W Ryan, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Villano, Danylo J, Zheng, Tongzhang, Zhang, Yawei, Holford, Theodore R, Turner, Jenny, Southey, Melissa C, Clavel, Jacqueline, Virtamo, Jarmo, Weinstein, Stephanie, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Boeing, Heiner, Tjønneland, Anne, Angelucci, Emanuele, Di Lollo, Simonetta, Rais, Marco, De Vivo, Immaculata, Giovannucci, Edward, Kraft, Peter, and Huang, Jinyan

Subjects
Clinical Research, Rare Diseases, Genetics, Cancer, Hematology, Lymphoma, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Lymphoma, B-Cell, Male, Middle Aged, Prospective Studies, Telomere, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

Published
2016

27. Clinical outcomes with use of radiation therapy and risk of transformation in early-stage follicular lymphoma

Author

Sha, Fushen, Okwali, Michelle, Alperovich, Anna, Caron, Philip C., Falchi, Lorenzo, Hamilton, Audrey, Hamlin, Paul A., Horwitz, Steven M., Joffe, Erel, Khan, Niloufer, Kumar, Anita, Matasar, Matthew J., Moskowitz, Alison J., Noy, Ariela, Owens, Colette, Palomba, Lia M., Rodriguez-Rivera, Ildefonso, Straus, David, von Keudell, Gottfried, Zelenetz, Andrew D., Yahalom, Joachim, Dogan, Ahmet, Schöder, Heiko, Seshan, Venkatraman E., Salles, Gilles, Younes, Anas, and Batlevi, Connie L.

Published
2022
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28. Management of adverse events associated with idelalisib treatment: expert panel opinion

Author

Coutré, Steven E, Barrientos, Jacqueline C, Brown, Jennifer R, de Vos, Sven, Furman, Richard R, Keating, Michael J, Li, Daniel, O’Brien, Susan M, Pagel, John M, Poleski, Martin H, Sharman, Jeff P, Yao, Nai-Shun, and Zelenetz, Andrew D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cancer, Patient Safety, Digestive Diseases, Development of treatments and therapeutic interventions, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, 5.1 Pharmaceuticals, Good Health and Well Being, Algorithms, Antineoplastic Agents, Class Ia Phosphatidylinositol 3-Kinase, Diet Therapy, Disease Management, Drug-Related Side Effects and Adverse Reactions, Enzyme Inhibitors, Expert Testimony, Hematologic Neoplasms, Humans, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Purines, Quinazolinones, Signal Transduction, TOR Serine-Threonine Kinases, Treatment Outcome, Idelalisib, phosphatidylinositol 3-kinase delta (PI3K) inhibitor, diarrhea, colitis, transaminitis, pneumonitis, phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, Immunology, Cardiovascular medicine and haematology
Abstract

Idelalisib is a first-in-class selective, oral, phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor approved for the treatment of several types of blood cancer. Idelalisib has demonstrated significant efficacy and a tolerable safety profile in clinical trials. However, the US prescribing information contains a black box warning for fatal and/or severe diarrhea or colitis, hepatotoxicity, pneumonitis and intestinal perforation. An expert panel was convened to review the pathology of these treatment-emergent adverse events (TEAEs) to propose key management tools for patients receiving idelalisib therapy. This article provides an overview of idelalisib TEAEs reported in clinical trials, and a summary of the panel's recommendations for identification and management of idelalisib treatment-emergent diarrhea or colitis as well as a discussion of transaminitis and pneumonitis. For idelalisib-related diarrhea or colitis (including unresolved grade 2 and grade ≥ 3), after exclusion of infectious causes, the panel recommends individualized treatment with budesonide or oral or intravenous steroid therapy.

Published
2015

29. Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1.2015.

Author

Zelenetz, Andrew D, Gordon, Leo I, Wierda, William G, Abramson, Jeremy S, Advani, Ranjana H, Andreadis, C Babis, Bartlett, Nancy, Byrd, John C, Czuczman, Myron S, Fayad, Luis E, Fisher, Richard I, Glenn, Martha J, Habermann, Thomas M, Harris, Nancy Lee, Hoppe, Richard T, Horwitz, Steven M, Kelsey, Christopher R, Kim, Youn H, Krivacic, Susan, LaCasce, Ann S, Nademanee, Auayporn, Porcu, Pierluigi, Press, Oliver, Rabinovitch, Rachel, Reddy, Nishitha, Reid, Erin, Saad, Ayman A, Sokol, Lubomir, Swinnen, Lode J, Tsien, Christina, Vose, Julie M, Wilson, Lynn, Yahalom, Joachim, Zafar, Nadeem, Dwyer, Mary, and Sundar, Hema

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Orphan Drug, Hematology, Clinical Research, Rare Diseases, Lymphoma, Cancer, Algorithms, Comorbidity, Disease Management, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasm Staging, Prognosis, National comprehension cancer network, Oncology & Carcinogenesis, Oncology and carcinogenesis, Health services and systems
Abstract

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease, which are managed in the same way. The advent of novel monoclonal antibodies (ofatumumab and obinutuzumab) led to the development of effective chemoimmunotherapy regimens. The recently approved small molecule kinase inhibitors (ibrutinib and idelalisib) are effective treatment options for CLL in elderly patients with decreased tolerance for aggressive regimens and in patients with poor prognostic features who do not benefit from conventional chemoimmunotherapy regimens. This portion of the NCCN Guidelines for Non-Hodgkin's Lymphomas describes the recent specific to the incorporation of recently approved targeted therapies for the management of patients with newly diagnosed and relapsed or refractory CLL/SLL.

Published
2015

30. Prognostic risk score for patients with relapsed or refractory chronic lymphocytic leukaemia treated with targeted therapies or chemoimmunotherapy: a retrospective, pooled cohort study with external validations

Author

Soumerai, Jacob D, Ni, Ai, Darif, Mohamed, Londhe, Anil, Xing, Guan, Mun, Yong, Kay, Neil E, Shanafelt, Tait D, Rabe, Kari G, Byrd, John C, Chanan-Khan, Asher A, Furman, Richard R, Hillmen, Peter, Jones, Jeffrey, Seymour, John F, Sharman, Jeffrey P, Ferrante, Lucille, Mobasher, Mehrdad, Stark, Thomas, Reddy, Vijay, Dreiling, Lyndah K, Bhargava, Pankaj, Howes, Angela, James, Danelle F, and Zelenetz, Andrew D

Published
2019
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32. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Author

Cerhan, James R, Berndt, Sonja I, Vijai, Joseph, Ghesquières, Hervé, McKay, James, Wang, Sophia S, Wang, Zhaoming, Yeager, Meredith, Conde, Lucia, de Bakker, Paul IW, Nieters, Alexandra, Cox, David, Burdett, Laurie, Monnereau, Alain, Flowers, Christopher R, De Roos, Anneclaire J, Brooks-Wilson, Angela R, Lan, Qing, Severi, Gianluca, Melbye, Mads, Gu, Jian, Jackson, Rebecca D, Kane, Eleanor, Teras, Lauren R, Purdue, Mark P, Vajdic, Claire M, Spinelli, John J, Giles, Graham G, Albanes, Demetrius, Kelly, Rachel S, Zucca, Mariagrazia, Bertrand, Kimberly A, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Hutchinson, Amy, Zhi, Degui, Habermann, Thomas M, Link, Brian K, Novak, Anne J, Dogan, Ahmet, Asmann, Yan W, Liebow, Mark, Thompson, Carrie A, Ansell, Stephen M, Witzig, Thomas E, Weiner, George J, Veron, Amelie S, Zelenika, Diana, Tilly, Hervé, Haioun, Corinne, Molina, Thierry Jo, Hjalgrim, Henrik, Glimelius, Bengt, Adami, Hans-Olov, Bracci, Paige M, Riby, Jacques, Smith, Martyn T, Holly, Elizabeth A, Cozen, Wendy, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Tinker, Lesley F, North, Kari E, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, Lightfoot, Tracy, Crouch, Simon, Smith, Alex, Roman, Eve, Diver, W Ryan, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Villano, Danylo J, Zheng, Tongzhang, Zhang, Yawei, Holford, Theodore R, Kricker, Anne, Turner, Jenny, Southey, Melissa C, Clavel, Jacqueline, Virtamo, Jarmo, Weinstein, Stephanie, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Trichopoulos, Dimitrios, Vermeulen, Roel CH, Boeing, Heiner, Tjonneland, Anne, Angelucci, Emanuele, Di Lollo, Simonetta, Rais, Marco, and Birmann, Brenda M

Subjects
Human Genome, Rare Diseases, Genetics, Cancer, Hematology, Lymphoma, Aetiology, 2.1 Biological and endogenous factors, Chromosome Mapping, Computational Biology, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Likelihood Functions, Lymphoma, Large B-Cell, Diffuse, Polymorphism, Single Nucleotide, Quantitative Trait Loci, White People, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

Published
2014

33. Non-Hodgkin's lymphomas, version 4.2014.

Author

Zelenetz, Andrew D, Gordon, Leo I, Wierda, William G, Abramson, Jeremy S, Advani, Ranjana H, Andreadis, C Babis, Bartlett, Nancy, Byrd, John C, Czuczman, Myron S, Fayad, Luis E, Fisher, Richard I, Glenn, Martha J, Harris, Nancy Lee, Hoppe, Richard T, Horwitz, Steven M, Kelsey, Christopher R, Kim, Youn H, Krivacic, Susan, LaCasce, Ann S, Nademanee, Auayporn, Porcu, Pierluigi, Press, Oliver, Rabinovitch, Rachel, Reddy, Nishitha, Reid, Erin, Saad, Ayman A, Sokol, Lubomir, Swinnen, Lode J, Tsien, Christina, Vose, Julie M, Yahalom, Joachim, Zafar, Nadeem, Dwyer, Mary, and Sundar, Hema

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Cancer, Hematology, Rare Diseases, Stem Cell Research, Lymphoma, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, Humans, Lymphoma, Non-Hodgkin, Neoplasm Staging, Recurrence, National comprehensive cancer network, Oncology & Carcinogenesis, Oncology and carcinogenesis, Health services and systems
Abstract

Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Mantle cell lymphoma (MCL) accounts for approximately 6% of all newly diagnosed NHL cases. Radiation therapy with or without systemic therapy is a reasonable approach for the few patients who present with early-stage disease. Rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR) is recommended for patients presenting with advanced-stage disease. Induction therapy followed by rituximab maintenance may provide extended disease control for those who are not candidates for HDT/ASCR. Ibrutinib, a Bruton tyrosine kinase inhibitor, was recently approved for the treatment of relapsed or refractory disease. This manuscript discusses the recommendations outlined in the NCCN Guidelines for NHL regarding the diagnosis and management of patients with MCL.

Published
2014

34. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia

Author

Furman, Richard R, Sharman, Jeff P, Coutre, Steven E, Cheson, Bruce D, Pagel, John M, Hillmen, Peter, Barrientos, Jacqueline C, Zelenetz, Andrew D, Kipps, Thomas J, Flinn, Ian, Ghia, Paolo, Eradat, Herbert, Ervin, Thomas, Lamanna, Nicole, Coiffier, Bertrand, Pettitt, Andrew R, Ma, Shuo, Stilgenbauer, Stephan, Cramer, Paula, Aiello, Maria, Johnson, Dave M, Miller, Langdon L, Li, Daniel, Jahn, Thomas M, Dansey, Roger D, Hallek, Michael, and O'Brien, Susan M

Subjects
Cancer, Lymphoma, Clinical Research, Clinical Trials and Supportive Activities, Hematology, Patient Safety, Rare Diseases, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Disease-Free Survival, Double-Blind Method, Female, Humans, Kaplan-Meier Estimate, Kidney Diseases, Leukemia, Lymphocytic, Chronic, B-Cell, Lymph Nodes, Male, Middle Aged, Phosphoinositide-3 Kinase Inhibitors, Purines, Quinazolinones, Recurrence, Rituximab, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundPatients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with acceptable side-effect profiles are needed for this patient population.MethodsIn this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo. We randomly assigned 220 patients with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily. The primary end point was progression-free survival. At the first prespecified interim analysis, the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy.ResultsThe median progression-free survival was 5.5 months in the placebo group and was not reached in the idelalisib group (hazard ratio for progression or death in the idelalisib group, 0.15; P

Published
2014

35. Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas.

Author

Soumerai, Jacob D., Diefenbach, Catherine S., Jagadeesh, Deepa, Asch, Adam, Kumar, Abhijeet, Tsai, Michaela L., Jandl, Thomas A., Lossos, Izidore S., Kenkre, Vaishalee P., Awan, Farrukh, Novotny, William, Huang, Jane, Miao, Lu, Rajagopalan, Prabhu, Ghalie, Richard G., and Zelenetz, Andrew D.

Subjects
BRUTON tyrosine kinase, LYMPHOMAS, FOLLICULAR lymphoma, PHOSPHATIDYLINOSITOL 3-kinases, ASPARTATE aminotransferase, MANTLE cell lymphoma
Abstract

Summary: The combination of the phosphatidylinositol 3‐kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single‐agent therapy. This phase 1 study (NCT02914938) included a dose‐finding stage in patients with relapsed/refractory (R/R) B‐cell malignancies (n = 20) and disease‐specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1–7 plus zanubrutinib 80 mg twice daily continuously in 28‐day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3–4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression‐free survival (PFS) were not reached in either group. The estimated 1‐year PFS was 72.3% (95% confidence interval [CI], 51.9–85.1) for FL and 56.3% (95% CI, 28.9–76.7) for MCL (median follow‐up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone. [ABSTRACT FROM AUTHOR]

Published
2024
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36. IBCL-271 Primary Efficacy and Safety Analysis of a Global Phase II Study of Zandelisib Administered by Intermittent Dosing (ID) in Patients With Relapsed or Refractory (R/R) Follicular Lymphoma (FL): The TIDAL Study

Author

Phillips, Tycel, Jurczak, Wojciech, Ribrag, Vincent, Linton, Kim, Collin, Graham P., Lopéz-Jimenéz, Javier, Reddy, Nishitha, Mengarelli, Andrea, Musuraca, Gerardo, Sheehy, Oonagh, Xu, Weiming, Azoulay, Michel, Ghalie, Richard G., Zinzani, Pier Luigi, and Zelenetz, Andrew D.

Published
2022
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38. Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis

Author

Casulo, Carla, Friedberg, Jonathan W., Ahn, Kwang W., Flowers, Christopher, DiGilio, Alyssa, Smith, Sonali M., Ahmed, Sairah, Inwards, David, Aljurf, Mahmoud, Chen, Andy I., Choe, Hannah, Cohen, Jonathon, Copelan, Edward, Farooq, Umar, Fenske, Timothy S., Freytes, Cesar, Gaballa, Sameh, Ganguly, Siddhartha, Jethava, Yogesh, Kamble, Rammurti T., Kenkre, Vaishalee P., Lazarus, Hillard, Lazaryan, Aleksandr, Olsson, Richard F., Rezvani, Andrew R., Rizzieri, David, Seo, Sachiko, Shah, Gunjan L., Shah, Nina, Solh, Melham, Sureda, Anna, William, Basem, Cumpston, Aaron, Zelenetz, Andrew D., Link, Brian K., and Hamadani, Mehdi

Published
2018
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39. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Author

Berndt, Sonja I, Skibola, Christine F, Joseph, Vijai, Camp, Nicola J, Nieters, Alexandra, Wang, Zhaoming, Cozen, Wendy, Monnereau, Alain, Wang, Sophia S, Kelly, Rachel S, Lan, Qing, Teras, Lauren R, Chatterjee, Nilanjan, Chung, Charles C, Yeager, Meredith, Brooks-Wilson, Angela R, Hartge, Patricia, Purdue, Mark P, Birmann, Brenda M, Armstrong, Bruce K, Cocco, Pierluigi, Zhang, Yawei, Severi, Gianluca, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Burdette, Laurie, Yuenger, Jeffrey, Hutchinson, Amy, Jacobs, Kevin B, Call, Timothy G, Shanafelt, Tait D, Novak, Anne J, Kay, Neil E, Liebow, Mark, Wang, Alice H, Smedby, Karin E, Adami, Hans-Olov, Melbye, Mads, Glimelius, Bengt, Chang, Ellen T, Glenn, Martha, Curtin, Karen, Cannon-Albright, Lisa A, Jones, Brandt, Diver, W Ryan, Link, Brian K, Weiner, George J, Conde, Lucia, Bracci, Paige M, Riby, Jacques, Holly, Elizabeth A, Smith, Martyn T, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Becker, Nikolaus, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, McKay, James, Staines, Anthony, Rabe, Kari G, Achenbach, Sara J, Vachon, Celine M, Goldin, Lynn R, Strom, Sara S, Lanasa, Mark C, Spector, Logan G, Leis, Jose F, Cunningham, Julie M, Weinberg, J Brice, Morrison, Vicki A, Caporaso, Neil E, Norman, Aaron D, Linet, Martha S, De Roos, Anneclaire J, Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Trichopoulos, Dimitrios, Masala, Giovanna, Weiderpass, Elisabete, Chirlaque, María-Dolores, Vermeulen, Roel CH, Travis, Ruth C, Giles, Graham G, Albanes, Demetrius, Virtamo, Jarmo, Weinstein, Stephanie, Clavel, Jacqueline, Zheng, Tongzhang, Holford, Theodore R, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Spinelli, John J, and Bertrand, Kimberly A

Subjects
Cancer, Case-Control Studies, Chromosomes, Human, Pair 2, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Recombination, Genetic, Risk, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

Published
2013

40. Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy

Author

Crombie, Jennifer L., Graff, Tara, Falchi, Lorenzo, Karimi, Yasmin H., Bannerji, Rajat, Nastoupil, Loretta, Thieblemont, Catherine, Ursu, Renata, Bartlett, Nancy, Nachar, Victoria, Weiss, Jonathan, Osterson, Jane, Patel, Krish, Brody, Joshua, Abramson, Jeremy S., Lunning, Matthew, Shah, Nirav N., Ayed, Ayed, Kamdar, Manali, Parsons, Benjamin, Caimi, Paolo, Flinn, Ian, Herrera, Alex, Sharman, Jeffrey, McKenna, Marshall, Armand, Philippe, Kahl, Brad, Smith, Sonali, Zelenetz, Andrew, Budde, Lihua Elizabeth, Hutchings, Martin, Phillips, Tycel, and Dickinson, Michael

Published
2024
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41. Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma

Author

Moskowitz, Alison J., Schöder, Heiko, Gavane, Somali, Thoren, Katie L., Fleisher, Martin, Yahalom, Joachim, McCall, Susan J., Cadzin, Briana R., Fox, Stephanie Y., Gerecitano, John, Grewal, Ravinder, Hamlin, Paul A., Horwitz, Steven M., Kumar, Anita, Matasar, Matthew, Ni, Andy, Noy, Ariela, Palomba, M. Lia, Perales, Miguel-Angel, Portlock, Carol S., Sauter, Craig, Straus, David, Younes, Anas, Zelenetz, Andrew D., and Moskowitz, Craig H.

Published
2017
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42. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial

Author

Zelenetz, Andrew D, Barrientos, Jacqueline C, Brown, Jennifer R, Coiffier, Bertrand, Delgado, Julio, Egyed, Miklós, Ghia, Paolo, Illés, Árpád, Jurczak, Wojciech, Marlton, Paula, Montillo, Marco, Morschhauser, Franck, Pristupa, Alexander S, Robak, Tadeusz, Sharman, Jeff P, Simpson, David, Smolej, Lukáš, Tausch, Eugen, Adewoye, Adeboye H, Dreiling, Lyndah K, Kim, Yeonhee, Stilgenbauer, Stephan, and Hillmen, Peter

Published
2017
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43. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups

Author

Batlevi, Connie L., Sha, Fushen, Alperovich, Anna, Ni, Ai, Smith, Katy, Ying, Zhitao, Soumerai, Jacob D., Caron, Philip C., Falchi, Lorenzo, Hamilton, Audrey, Hamlin, Paul A., Horwitz, Steven M., Joffe, Erel, Kumar, Anita, Matasar, Matthew J., Moskowitz, Alison J., Moskowitz, Craig H., Noy, Ariela, Owens, Colette, Palomba, Lia M., Straus, David, von Keudell, Gottfried, Zelenetz, Andrew D., Seshan, Venkatraman E., and Younes, Anas

Published
2020
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44. Phase I study of bendamustine, rituximab, ibrutinib, and venetoclax in relapsed, refractory mantle cell lymphoma.

Author

Grieve, Clare, Joseph, Ashlee, Drullinsky, Pamela, Zelenetz, Andrew D., Hamlin, Paul, and Kumar, Anita

Subjects
VENETOCLAX, RITUXIMAB, MANTLE cell lymphoma
Abstract

This dose-finding study evaluated safety of venetoclax plus Bendamustine-Rituximab-Ibrutinib in relapsed/refractory MCL. Six 28-day cycles were administered in a 3 + 3 dose-escalation design. Dose level 1 (DL1) included Bendamustine 90 mg/m2 on day 1-2, Rituximab 375 mg/m2 on day 1, and Ibrutinib 560 mg daily. Venetoclax was dosed with ramp-up and at 400 mg starting in Cycle 2 for 5 days. The most common adverse events were thrombocytopenia (80%), constipation (60%), and fatigue (60%). Rare hematologic grade 3-4 AEs, 1 dose-limiting toxicity at DL1 (prolonged grade 3 thrombocytopenia), and delayed hematologic toxicity were observed. DL-1 with Bendamustine dose-reduced to 70 mg/m2 (n = 3) revealed no significant toxicity. The overall and complete response rates were both 80% (8/10). This study underscored that venetoclax combined with chemoimmunotherapy is complicated by hematologic toxicity, limiting future development. Although a maximum tolerated dose was not formally established given early study closure, this study demonstrated preliminary tolerability and efficacy of Bendamustine-Rituximab-Ibrutinib-Venetoclax at DL-1. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Gemcitabine plus pembrolizumab after checkpoint blockade failure as a strategy in multiply relapsed Hodgkin lymphoma.

Author

Stuver, Robert, Noy, Ariela, Vardhana, Santosha A., Zelenetz, Andrew D., and Moskowitz, Alison J.

Subjects
HODGKIN'S disease, HISTOCOMPATIBILITY class I antigens, GEMCITABINE, PEMBROLIZUMAB
Abstract

This article discusses the use of gemcitabine plus pembrolizumab as a treatment strategy for patients with multiply relapsed Hodgkin lymphoma (HL) who have experienced disease progression after checkpoint inhibitor therapy. The study retrospectively identified 13 patients who were treated with gemcitabine and pembrolizumab, and found that 11 patients achieved a response, including five complete responses. The addition of gemcitabine to pembrolizumab may be a potential strategy for patients with multiply relapsed HL, particularly after prior checkpoint blockade failure. However, the exact mechanism of response is unclear and further research is needed. [Extracted from the article]

Published
2024
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47. Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma

Author

Kumar, Anita, Casulo, Carla, Yahalom, Joachim, Schöder, Heiko, Barr, Paul M., Caron, Philip, Chiu, April, Constine, Louis S., Drullinsky, Pamela, Friedberg, Jonathan W., Gerecitano, John F., Hamilton, Audrey, Hamlin, Paul A., Horwitz, Steven M., Jacob, Alexandra G., Matasar, Matthew J., McArthur, Gianna N., McCall, Susan J., Moskowitz, Alison J., Noy, Ariela, Palomba, Maria L., Portlock, Carol S., Straus, David J., VanderEls, Nicholas, Verwys, Stephanie L., Yang, Joanna, Younes, Anas, Zelenetz, Andrew D., Zhang, Zhigang, and Moskowitz, Craig H.

Published
2016
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48. Clinicogenetic risk models predict early progression of follicular lymphoma after first-line immunochemotherapy

Author

Jurinovic, Vindi, Kridel, Robert, Staiger, Annette M., Szczepanowski, Monika, Horn, Heike, Dreyling, Martin H., Rosenwald, Andreas, Ott, German, Klapper, Wolfram, Zelenetz, Andrew D., Barr, Paul M., Friedberg, Jonathan W., Ansell, Stephen, Sehn, Laurie H., Connors, Joseph M., Gascoyne, Randy D., Hiddemann, Wolfgang, Unterhalt, Michael, Weinstock, David M., and Weigert, Oliver

Published
2016
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