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https://www.readbyqxmd.com/read/28453705/optimal-sequencing-of-ibrutinib-idelalisib-and-venetoclax-in-chronic-lymphocytic-leukemia-results-from-a-multicenter-study-of-683-patients
#1
A R Mato, B T Hill, N Lamanna, P M Barr, C S Ujjani, D M Brander, C Howlett, A P Skarbnik, B D Cheson, C S Zent, J J Pu, P Kiselev, K Foon, J Lenhart, S Henick Bachow, A M Winter, A-L Cruz, D F Claxton, A Goy, C Daniel, K Isaac, K H Kennard, C Timlin, M Fanning, L Gashonia, M Yacur, J Svoboda, S J Schuster, C Nabhan
Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS)...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28446054/pharmacotherapy-of-relapsed-refractory-chronic-lymphocytic-leukemia
#2
Abdallah Abou Zahr, Prithviraj Bose, Michael J Keating
The treatment of relapsed/refractory (RR) CLL has been revolutionized by the advent of the new oral inhibitors of B-cell receptor (BCR) signaling and the pro-survival protein, B-cell lymphoma 2 (BCL2). Additionally, new and more potent monoclonal antibodies against CD20 have replaced/may replace rituximab in many settings. Areas covered: Herein, we review the entire therapeutic landscape of RR CLL, with particular attention to the new small-molecule kinase inhibitors and BH3-mimetics. We discuss preclinical data with these agents in CLL, cover available efficacy and safety information, and examine potential resistance mechanisms and possible rational combinations to circumvent them...
April 26, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28430865/unmet-needs-in-the-first-line-treatment-of-follicular-lymphoma
#3
C Casulo, L Nastoupil, N H Fowler, J W Friedberg, C R Flowers
For the majority of patients with newly diagnosed follicular lymphoma (FL), current treatments, while not curative, allow for long remission durations. However, several important needs remain unaddressed. Studies have consistently shown that approximately 20% of patients with FL experience disease progression within 2 years of first-line treatment, and consequently have a 50% risk of death in 5 years. Better characterization of this group of patients at diagnosis may provide insight into those in need of alternate or intensive therapies, facilitate a precision approach to inform clinical trials, and allow for improved patient counseling...
April 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28427156/the-effects-of-dleu1-gene-expression-in-burkitt-lymphoma-bl-potential-mechanism-of-chemoimmunotherapy-resistance-in-bl
#4
Sanghoon Lee, Wen Luo, Tishi Shah, Changhong Yin, Timmy O'Connell, Tae-Hoon Chung, Sherrie L Perkins, Rodney R Miles, Janet Ayello, Erin Morris, Lauren Harrison, Carmella van de Ven, Mitchell S Cairo
Following a multivariant analysis we demonstrated that children and adolescents with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in event free survival (EFS) despite identical short intensive multi-agent chemotherapy. However, how this deletion in the 13q14.3 region is associated with a significant decrease in EFS in children and adolescents with BL is largely unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the region of 13q14.3. Here, we report that DLEU1 expression is implicated in the regulation of BL programmed cell death, cell proliferation, and expression of apoptotic genes in transcription activator-like effector nuclease (TALEN)s-induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408615/phase-ii-study-of-bortezomib-in-combination-with-cyclophosphamide-and-rituximab-for-relapsed-or-refractory-mantle-cell-lymphoma
#5
Hun Ju Lee, Jorge E Romaguera, Lei Feng, Aakash P Desai, Liang Zhang, Michelle Fanale, Felipe Samaniego, Fredrick B Hagemeister, Luis E Fayad, Maria A Rodriguez, Jeffrey L Medeiros, Kimberly Hartig, Krystle Nomie, Makhdum Ahmed, Maria Badillo, Haige Ye, Yasuhiro Oki, Pei Lin, Loretta Nastoupil, Jason Westin, Michael Wang
BACKGROUND: Relapsed or refractory mantle cell lymphoma (MCL) has a poor prognosis. The best outcome is achieved in patients who have a partial or complete response to salvage treatment and proceed to allogeneic stem cell transplant. PATIENTS AND METHODS: Twenty-one patients were given a combination regimen of bortezomib, cyclophosphamide, and rituximab at MD Anderson Cancer Center as part of a single-arm, prospective, open-label phase II clinical trial. The median age was 66 years, with a median number of prior treatments of three...
April 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28402624/near-infrared-photochemoimmunotherapy-by-photoactivatable-bifunctional-antibody-drug-conjugates-targeting-her2-positive-cancer
#6
Kimihiro Ito, Makoto Mitsunaga, Takashi Nishimura, Masayuki Saruta, Takeo Iwamoto, Hisataka Kobayashi, Hisao Tajiri
Near-infrared photoimmunotherapy (NIR-PIT) is a new class of molecular targeted cancer therapy based on antibody-photoabsorber conjugates and NIR light irradiation. Recent studies have shown effective tumor control, including that of human epidermal growth factor receptor 2 (HER2)-positive cancer, by selective molecular targeting with NIR-PIT. However, the depth of NIR light penetration limits its use. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate consisting of the monoclonal antibody trastuzumab linked to the cytotoxic agent maytansinoid DM1...
April 12, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28402581/akt-inhibitor-mk-2206-in-combination-with-bendamustine-and-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukemia-results-from-the-n1087-alliance-study
#7
Jeremy T Larsen, Tait D Shanafelt, Jose F Leis, Betsy LaPlant, Tim Call, Adam Pettinger, Curtis Hanson, Charles Erlichman, Thomas Matthew Habermann, Craig Reeder, Daniel Nikcevich, Deborah Bowen, Michael Conte, Justin Boysen, Charla Secreto, Connie Lesnick, Renee Tschumper, Diane Jelinek, Neil E Kay, Wei Ding
Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK-2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK-2206 in combination with BR in relapsed CLL. Single-agent MK-2206 (weekly dosed) was administered one-week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2-6...
April 12, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28389687/advances-in-the-treatment-of-relapsed-refractory-chronic-lymphocytic-leukemia
#8
REVIEW
C Shustik, I Bence-Bruckler, R Delage, C J Owen, C L Toze, S Coutre
Treatment of chronic lymphocytic leukemia (CLL) has advanced with the introduction of chemoimmunotherapy (CIT) agents that have improved the outcomes of frontline therapy. However, most treated patients will relapse and require subsequent therapy. This review focuses on recent advances in the treatment of relapsed or refractory CLL. Until recently, treatment options for relapsed CLL were of limited efficacy. Retreatment with fludarabine, cyclophosphamide, and rituximab (FCR) was recommended for patients with a durable response to first-line FCR, although acquired genetic aberrations, impaired marrow reserve, and comorbidities often made this suboptimal therapy for many patients...
April 7, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28367250/milestones-in%C3%A2-chronic-lymphocytic-leukemia-an-exciting-decade-of-progress-10th-anniversary-of-memo
#9
REVIEW
Alexander Egle
The past 10 years have been an exciting ride for Chronic Lymphocytic Leukemia (CLL) aficionados. An overview of changes in management paradigms in CLL, ranging from insights into biology, via chemotherapy and chemoimmunotherapy to maintenance and novel drugs will be presented.
2017: Memo
https://www.readbyqxmd.com/read/28325864/idelalisib-is-effective-in-patients-with-high-risk-follicular-lymphoma-and-early-relapse-after-initial-chemoimmunotherapy
#10
Ajay K Gopal, Brad S Kahl, Christopher R Flowers, Peter Martin, Stephen M Ansell, Esteban Abella-Dominicis, Brian Koh, Wei Ye, Paul M Barr, Gilles A Salles, Jonathan W Friedberg
No abstract text is available yet for this article.
March 21, 2017: Blood
https://www.readbyqxmd.com/read/28295729/targeting-of-b-cell-receptor-signalling-in-b-cell-malignancies
#11
M Jerkeman, M Hallek, M Dreyling, C Thieblemont, E Kimby, L Staudt
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28276536/obinutuzumab-in-follicular-lymphoma
#12
N Martinez-Calle, R Figueroa-Mora, S Villar-Fernandez, M Marcos-Jubilar, C Panizo
The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens...
December 2016: Drugs of Today
https://www.readbyqxmd.com/read/28275031/nccn-guidelines-insights-chronic-lymphocytic-leukemia-small-lymphocytic-leukemia-version-1-2017
#13
William G Wierda, Andrew D Zelenetz, Leo I Gordon, Jeremy S Abramson, Ranjana H Advani, C Babis Andreadis, Nancy Bartlett, John C Byrd, Paolo Caimi, Luis E Fayad, Richard I Fisher, Martha J Glenn, Thomas M Habermann, Nancy Lee Harris, Francisco Hernandez-Ilizaliturri, Richard T Hoppe, Steven M Horwitz, Mark S Kaminski, Christopher R Kelsey, Youn H Kim, Susan Krivacic, Ann S LaCasce, Michael G Martin, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A Saad, Erin D Snyder, Lubomir Sokol, Lode J Swinnen, Julie M Vose, Joachim Yahalom, Mary A Dwyer, Hema Sundar
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL...
March 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28271950/novel-agents-versus-chemotherapy-as-frontline-treatment-of-cll
#14
Anna Piggin, Emma Bayly, Constantine S Tam
Chronic lymphocytic leukemia (CLL) is a neoplastic disorder of mature B lymphocytes. While traditionally treated with combinations of chemoimmunotherapy, the therapeutic options for CLL have expanded in recent years with the emergence of novel oral agents, such as the Bruton tyrosine kinase inhibitor ibrutinib, that are well tolerated and highly efficacious. The role of novel agents in the first-line setting is now being investigated in head-to-head clinical trials. In this discussion paper, we consider the role of novel agents in the up-front setting, using three case studies of treatment-naive patients to highlight how choice of therapy may be individualized depending on the characteristics of the patient and the disease, as well as patient preferences...
June 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28262268/how-gene-polymorphisms-can-influence-clinical-response-and-toxicity-following-r-chop-therapy-in-patients-with-diffuse-large-b-cell-lymphoma
#15
REVIEW
Angela Falduto, Francesco Cimino, Antonio Speciale, Caterina Musolino, Sebastiano Gangemi, Antonella Saija, Alessandro Allegra
The treatment of diffuse large B cell lymphoma (DLBCL) is generally based on multidrug chemotherapy, for instance the therapy with rituximab together with cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP). A significant proportion of DLBCL patients benefit from rituximab-based chemoimmunotherapy. However, among patients with DLBCL toxic effects due to therapy treatment are still very frequent, as well as inter-individual differences in the outcomes of patients even having similar stage, histological grade and histopathological type of the tumor...
February 27, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28246553/the-role-of-combined-fludarabine-cyclophosphamide-and-rituximab-chemoimmunotherapy-in-chronic-lymphocytic-leukemia-current-evidence-and-controversies
#16
REVIEW
Alan P Skarbnik, Stefan Faderl
Chemoimmunotherapy (CIT) has become a cornerstone in the treatment of patients with chronic lymphocytic leukemia (CLL). The combination of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as the standard of care for therapy of previously untreated patients with CLL who are younger than 65 years and have no significant comorbidities. In this article, we review the role of FCR in the current treatment paradigm for CLL.
March 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28245410/-research-progress-of-novel-small-molecule-drugs-in-the-treatment-of-chronic-lymphocytic-leukemia-review
#17
Jing-Qiao Qiao, Miao He, Shu-Ting Zhang, Hai Bai
Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western population, is characterized by accumulation of mature-looking CD5(+)/19(+)/23(+) B cells in peripheral blood, bone marrow, and lymphatic organs. Over the last 20 years, there has been a dramatic change in therapy for CLL, the complete response rate increased from the initial <5% to the current 40%-50%, this remarkable improvement has been attributable to combination of chemoimmunotherapy agents that have contributed to the backbone of therapy for patients with CLL...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28237865/the-number-of-extranodal-sites-assessed-by-pet-ct-scan-is-a-powerful-predictor-of-cns-relapse-for-patients-with-diffuse-large-b-cell-lymphoma-an-international-multicenter-study-of-1532-patients-treated-with-chemoimmunotherapy
#18
Tarec Christoffer El-Galaly, Diego Villa, Thomas Yssing Michaelsen, Martin Hutchings, Nabegh George Mikhaeel, Kerry J Savage, Laurie H Sehn, Sally Barrington, Jakob W Hansen, Daniel Smith, Kirsty Rady, Karen J Mylam, Thomas S Larsen, Staffan Holmberg, Maja B Juul, Sabrina Cordua, Michael R Clausen, Kristina B Jensen, Hans E Johnsen, John F Seymour, Joseph M Connors, Peter de Nully Brown, Martin Bøgsted, Chan Y Cheah
PURPOSE: Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. METHODS: We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens...
April 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28223822/profile-of-venetoclax-and-its-potential-in-the-context-of-treatment-of-relapsed-or-refractory-chronic-lymphocytic-leukemia
#19
REVIEW
Henriette Huber, Simone Edenhofer, Sven Estenfelder, Stephan Stilgenbauer
Over the last few years, dramatic changes have occurred in the treatment of chronic lymphocytic leukemia (CLL). The current standard for young and fit patients with CLL remains chemoimmunotherapy, namely the fludarabine, cyclophosphamide, and rituximab (FCR) regimen. However, novel oral therapies are presently being introduced and represent a considerable breakthrough concerning effectiveness and safety profile. In particular, the very high-risk group of CLL patients, defined by the genetic aberration del(17p) and/or TP53 mutation, benefit from the new agents...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28211162/efficacy-of-the-oral-mtorc1-inhibitor-everolimus-in-relapsed-or-refractory-indolent-lymphoma
#20
N Nora Bennani, Betsy R LaPlant, Stephen M Ansell, Thomas M Habermann, David J Inwards, Ivana N Micallef, Patrick B Johnston, Luis F Porrata, Joseph P Colgan, Svetomir N Markovic, Grzegorz S Nowakowski, William R Macon, Craig B Reeder, Joseph R Mikhael, Donald W Northfelt, Irene M Ghobrial, Thomas E Witzig
Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas...
February 17, 2017: American Journal of Hematology
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