Review
Oncology
Maria Chiara Barbanti, Niamh Appleby, Murali Kesavan, Toby Andrew Eyre
Summary: Cellular therapy, such as allogenic stem cell transplantation and chimeric antigen receptor T-cell therapy, continues to be explored in high-risk chronic lymphocytic leukemia and Richter syndrome. However, these treatment modalities have limitations and specific placement in treatment algorithms.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, General & Internal
J. R. Brown, B. Eichhorst, P. Hillmen, W. Jurczak, M. Kazmierczak, N. Lamanna, S. M. O'Brien, C. S. Tam, L. Qiu, K. Zhou, M. Simkovic, J. Mayer, A. Gillespie-Twardy, A. Ferrajoli, P. S. Ganly, R. Weinkove, S. Grosicki, A. Mital, T. Robak, A. Osterborg, H. A. Yimer, T. Salmi, M. -D. -Y. Wang, L. Fu, J. Li, K. Wu, A. Cohen, M. Shadman
Summary: In a multinational phase 3 trial, zanubrutinib was found to be superior to ibrutinib in treating relapsed or refractory CLL or SLL, with better efficacy and fewer side effects.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Anthony Mato
Summary: Significant progress has been made in the treatment of relapsed/refractory CLL and SLL, with targeted therapies replacing traditional chemotherapy as the standard of care for most patients.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2022)
Review
Hematology
Jennifer A. Woyach
Summary: The therapeutic landscape for CLL has changed dramatically with the development of oral therapies targeting key drivers, posing challenges in sequencing available treatments and raising questions on how to improve treatment continuously.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Review
Oncology
Oluwatobi Odetola, Shuo Ma
Summary: This review emphasizes that the purpose of treatment for relapsed/refractory CLL is disease control and delay of progression rather than cure. The article reviews the concept of relapsed CLL, factors predisposing to relapse, and available therapeutic options. Recent findings show that targeted therapies such as continuous BTK inhibitors or fixed duration venetoclax plus anti-CD20 monoclonal antibody therapy have established superiority over chemoimmunotherapy in relapsed CLL and are now the preferred standard of care treatment.
CURRENT HEMATOLOGIC MALIGNANCY REPORTS
(2023)
Article
Hematology
Noelle Frey
Summary: Brexucabtagene autoleucel has become the first anti-CD19 chimeric antigen receptor T-cell product approved by the FDA for the treatment of relapsed and refractory B-cell acute lymphoblastic leukemia, significantly expanding treatment options for patients.
Review
Oncology
Prioty Islam
Summary: The treatment of relapsed and refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) has undergone significant changes in the past decade with the development of oral targeted agents. The choice of treatment depends on prior exposure to novel therapies. Patients with no prior exposure are offered BTK or BCL2-based regimens, while those with prior BTK inhibitor exposure may receive a BCL2 inhibitor and vice versa. For intolerant patients, an alternative BTK inhibitor may be considered. Limited data support re-treatment with a BCL2 inhibitor-based regimen for patients who have maintained a response for more than 12-24 months. Clinical trials are preferred for patients who have failed both BTK and BCL2 inhibitors. High-risk populations may be considered for combination cytotoxic chemotherapy, allogeneic hematopoietic stem cell transplant, or cellular therapy, with the need for novel approaches and clinical trial enrollment.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2023)
Article
Hematology
Martin Spacek, Lukas Smolej, Martin Simkovic, Lucie Nekvindova, Zlatuse Kristkova, Yvona Brychtova, Anna Panovska, Stanislava Maslejova, Lucie Bezdekova, Dominika Ecsiova, Pavel Vodarek, Jana Zuchnicka, Jana Mihalyova, Renata Urbanova, Peter Turcsanyi, Daniel Lysak, Jan Novak, Martin Brejcha, Tereza Likarova, Prokop Vodicka, Jana Baranova, Marek Trneny, Michael Doubek
Summary: Idelalisib plus rituximab showed inferior efficacy and tolerability compared to ibrutinib in patients with relapsed/refractory CLL, but may still be considered in select cases.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Yuqin Song, Keshu Zhou, Shenmiao Yang, Jianda Hu, Dehui Zou, Sujun Gao, Ling Pan, Tingyu Wang, Haiyan Yang, Huilai Zhang, Daobin Zhou, Jie Ji, Wei Xu, Ru Feng, Jie Jin, Fangfang Lv, Haiwen Huang, Xiaosi Fan, Sheng Xu, Jun Zhu
Summary: We conducted two indirect comparisons to estimate the efficacy of zanubrutinib versus orelabrutinib in Chinese patients with relapsed or refractory CLL/SLL or MCL. The results showed that zanubrutinib demonstrated favorable PFS over orelabrutinib in R/R CLL/SLL patients and had favorable PFS and higher CR rate than orelabrutinib in R/R MCL patients.
INVESTIGATIONAL NEW DRUGS
(2023)
Article
Oncology
Liana Nikolaenko, Tingting Liu, Alexey V. Danilov
Summary: The treatment landscape of chronic lymphocytic leukemia (CLL) has been significantly altered with the introduction of novel targeted therapies, including PI3K inhibitors like idelalisib and duvelisib approved for therapy of relapsed/refractory (R/R) CLL. Duvelisib, a selective dual PI3K delta/gamma inhibitor, has shown meaningful efficacy in high-risk R/R CLL patients and may be particularly suitable for those who are suboptimal candidates for BTK inhibitors. Monitoring and managing adverse events is crucial for the continued role of duvelisib in therapy of R/R CLL.
EXPERT REVIEW OF ANTICANCER THERAPY
(2021)
Article
Oncology
Sikander Ailawadhi, Zi Chen, Bo Huang, Aneel Paulus, Mary C. Collins, Lei (Tommy) Fu, Mingyu Li, Mohammad Ahmad, Lichuang Men, Hengbang Wang, Matthew S. Davids, Eric Liang, Divya J. Mekala, Zhicong He, Masa Lasica, Costas K. Yannakou, Ricardo Parrondo, Laura Glass, Dajun Yang, Asher Chanan-Khan, Yifan Zhai
Summary: This global phase I trial aimed to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of lisaftoclax in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies (HMs). The results demonstrated that lisaftoclax was well tolerated, had a short plasma residence, and induced rapid clinical responses in R/R CLL/SLL patients.
CLINICAL CANCER RESEARCH
(2023)
Article
Hematology
Paolo Ghia, Andrzej Pluta, Malgorzata Wach, Daniel Lysak, Martin Simkovic, Iryna Kriachok, Arpad Illes, Javier de la Serna, Sean Dolan, Philip Campbell, Gerardo Musuraca, Abraham Jacob, Eric J. Avery, Jae Hoon Lee, Ganna Usenko, Min Hui Wang, Ting Yu, Wojciech Jurczak
Summary: Acalabrutinib demonstrated superior efficacy and acceptable tolerability in patients with R/R CLL, showing significantly prolonged progression-free survival compared to standard-of-care regimens.
Article
Hematology
Csaba Bodor, Lili Kotmayer, Tamas Laszlo, Ferenc Takacs, Gabor Barna, Richard Kiss, Endre Sebestyen, Tibor Nagy, Lajos Laszlo Hegyi, Gabor Mikala, Sandor Fekete, Peter Farkas, Alexandra Balogh, Tamas Masszi, Judit Demeter, Julia Weisinger, Hussain Alizadeh, Bela Kajtar, Zoltan Kohl, Robert Szasz, Lajos Gergely, Timea Gurbity Palfi, Adrienn Sulak, Balazs Kollar, Miklos Egyed, Mark Plander, Laszlo Rejto, Laszlo Szerafin, Peter Ilonczai, Peter Tamaska, Piroska Pettendi, Dora Levai, Tamas Schneider, Anna Sebestyen, Peter Csermely, Andras Matolcsy, Zoltan Matrai, Donat Alpar
Summary: The study found that the BTKC481S mutation is common in CLL patients and is associated with disease progression, appearing months before clinical relapse symptoms. Subsequent Bcl-2 inhibition therapy in patients with BTKC481S and progressing on ibrutinib treatment resulted in clinical and molecular remission.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Oncology
Peter Hillmen, Barbara Eichhorst, Jennifer R. Brown, Nicole Lamanna, Susan M. O'Brien, Constantine S. Tam, Lugui Qiu, Maciej Kazmierczak, Keshu Zhou, Martin Simkovic, Jiri Mayer, Amanda Gillespie-Twardy, Mazyar Shadman, Alessandra Ferrajoli, Peter S. Ganly, Robert Weinkove, Sebastian Grosicki, Andrzej Mital, Tadeusz Robak, Anders Osterborg, Habte A. Yimer, Tommi Salmi, Meng Ji, Jessica Yecies, Adam Idoine, Kenneth Wu, Jane Huang, Wojciech Jurczak
Summary: The study compared the efficacy and safety of zanubrutinib and ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The results showed that zanubrutinib had better outcomes in terms of efficacy, atrial fibrillation rate, and cardiac safety compared to ibrutinib.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Medicine, Research & Experimental
Xiao Tang, Wenrong Zou, Peng Peng, Yanglu Bai
Summary: The use of novel targeted drugs has significantly improved the overall response rate and survival of patients with relapsed/refractory chronic lymphocytic leukemia. Venetoclax, especially when combined with anti-CD20 monoclonal antibody, demonstrates effectiveness in treating these patients, particularly those with high-risk cytogenetic factors. Additionally, the combination of ibrutinib with venetoclax shows longer remission times and increased rates of deeper remission and uMRD-negativity with prolonged treatment.
CLINICAL AND EXPERIMENTAL MEDICINE
(2022)
Article
Oncology
Junan Li, Avinash K. Persaud, Jasmine A. Johnson, Dougkas W. Sborov, Mitch A. Phelps, Craig C. Hofmeister, Ming J. Poi
Summary: This study investigated the association of select single nucleotide polymorphisms in the SLC22A3 gene with clinical outcomes in multiple myeloma patients. The results suggested that a specific genotype was associated with altered melphalan transport and an increased risk of severe oral mucositis.
ANTICANCER RESEARCH
(2022)
Article
Hematology
Tanya Siddiqi, Jacob D. Soumerai, Kathleen A. Dorritie, Deborah M. Stephens, Peter A. Riedell, Jon Arnason, Thomas J. Kipps, Heidi H. Gillenwater, Lucy Gong, Lin Yang, Ken Ogasawara, Jerill Thorpe, William G. Wierda
Summary: Lisocabtagene maraleucel, an autologous CD19-directed CAR T-cell therapy, shows promising safety and efficacy in patients with relapsed/refractory CLL/SLL, providing a potential new treatment option for these patients who develop resistance to current therapies.
Article
Hematology
Swagata Goswami, Rajeswaran Mani, Jessica Nunes, Chi-Ling Chiang, Kevan Zapolnik, Eileen Hu, Frank Frissora, Xiaokui Mo, Logan A. Walker, Pearlly Yan, Ralf Bundschuh, Larry Beaver, Raymond Devine, Yo-Ting Tsai, Ann Ventura, Zhiliang Xie, Min Chen, Rosa Lapalombella, Alison Walker, Alice Mims, Karilyn Larkin, Nicole Grieselhuber, Chad Bennett, Mitch Phelps, Erin Hertlein, Gregory Behbehani, Sumithira Vasu, John C. Byrd, Natarajan Muthusamy
Summary: This study reveals that silencing of protein phosphatase 2A (PP2A) directly blocks differentiation in acute myeloid leukemia (AML). Activation of PP2A regulates cell cycle and transcriptional regulators, thereby modulating terminal myeloid differentiation. This finding highlights the potential therapeutic targeting of the PP2A/c-Myc/p21 axis in malignancies with dysregulated maturation fate.
Article
Oncology
Yizhen Guo, Lai Wei, Sandip H. Patel, Gabrielle Lopez, Madison Grogan, Mingjia Li, Tyler Haddad, Andrew Johns, Latha P. Ganesan, Yiping Yang, Daniel J. Spakowicz, Peter G. Shields, Kai He, Erin M. Bertino, Gregory A. Otterson, David P. Carbone, Carolyn Presley, Samuel K. Kulp, Thomas A. Mace, Christopher C. Coss, Mitch A. Phelps, Dwight H. Owen
Summary: Serum albumin and early albumin decrease are significantly associated with overall survival in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor (ICI) therapy. This study suggests that albumin changes may serve as potential biomarkers to predict treatment outcomes and warrant further investigation.
CLINICAL LUNG CANCER
(2022)
Letter
Hematology
Gage S. Black, Xiaomeng Huang, Yi Qiao, Szabolcs Tarapcsak, Kerry A. Rogers, Shrilekha Misra, John C. Byrd, Gabor T. Marth, Deborah M. Stephens, Jennifer A. Woyach
Article
Oncology
Deborah M. Stephens, Ying Huang, Amy S. Ruppert, Janek S. Walker, Casey B. Cempre, Qiang Fu, Sharyn Baker, Boyu Hu, Harsh Shah, Renee Vadeboncoeur, Kerry A. Rogers, Seema Bhat, Samantha M. Jaglowski, Hank Lockman, Rosa Lapalombella, John C. Byrd, Jennifer A. Woyach
Summary: The combination of selinexor and ibrutinib has demonstrated tolerability and durable responses in patients with relapsed/refractory CLL/NHL. Notable responses were seen in patients with CLL with minimal prior therapy.
CLINICAL CANCER RESEARCH
(2022)
Article
Dermatology
Dylan L. Burroughs, Gwendolen Lorch, Yizhen Guo, Kasey Hill, Eric L. Schroeder, Lynette K. Cole, Mitch A. Phelps
Summary: This study aimed to define the noncompartmental pharmacokinetic parameters of intravenous mycophenolate mofetil (MMF) and its downstream metabolites in healthy horses. The results showed that horses biotransform MMF into mycophenolic acid (MPA), MPA phenol glucuronide (MPAG), MPA acyl glucuronide (AcMPAG), and MPA phenol glucoside (MPG).
VETERINARY DERMATOLOGY
(2023)
Meeting Abstract
Hematology
Karen Sweiss, Pritesh Patel, Janet Guo, Kyeongmin Kim, Kasey Hill, Nicole Abbott, Jeremy Johnson, Donald Irby, John G. Quigley, Damiano Rondelli, R. Donald Harvey, Ajay K. Nooka, Madhav Dhodapkar, Jonathan L. Kaufman, Nisha S. Joseph, Sagar Lonial, Douglas W. Sborov, Mitch A. Phelps, Craig C. Hofmeister
Article
Oncology
Junan LI, Yu kyoung Cho, Douglas W. Sborov, Mitch A. Phelps, Craig C. Hofmeister, Ming J. Poi
Summary: This study aimed to evaluate the potential impacts of CYP3A4*1B and CYP3A5*3 gene variations on the pharmacokinetic properties of melphalan and clinical outcomes in multiple myeloma patients. The results showed that CYP3A4*1B/*1B and CYP3A5*3/*3 carriers had shorter median progression-free survival time and higher maximum melphalan plasma concentration. Through yet-to-be-identified mechanisms, CYP3A4*1B/*1B and CYP3A5*3/*3 variations might influence melphalan therapy in MM patients.
CANCER GENOMICS & PROTEOMICS
(2023)
Article
Hematology
Chaitra Ujjani, Ted A. Gooley, Stephen E. Spurgeon, Deborah M. Stephens, Catherine Lai, Catherine M. Broome, Susan O'Brien, Haiying Zhu, Kerry J. Laing, Allison M. Winter, Georgios Pongas, Alexander L. Greninger, David M. Koelle, Tanya Siddiqi, Matthew S. Davids, Kerry A. Rogers, Alexey V. Danilov, Amy Sperling, Brian Tu, Tyler Sorensen, Kelsey Launchbury, Carlissa J. Burrow, Genesis Quezada, Joshua A. Hill, Mazyar Shadman, Philip A. Thompson
Summary: This study aimed to analyze the immune responses of patients with chronic lymphocytic leukemia (CLL) to the COVID-19 vaccine, including T-cell responses, and the impact of CLL therapeutics. The study found that patients receiving B-cell-directed therapy were less likely to have immune conversion. Additionally, the immune response persisted at 6 months, and administration of booster vaccinations enhanced the immune response. However, caution should be exercised as newer variants emerge and escape vaccine-induced immunity.
Review
Pharmacology & Pharmacy
Kyeongmin Kim, Mitch A. A. Phelps
Summary: Daratumumab is a fully human monoclonal antibody used for the treatment of multiple myeloma and light-chain amyloidosis. It works by targeting CD38 and has demonstrated anti-myeloma activity through various mechanisms. The dosing schedule and exposure to daratumumab are important factors for its efficacy, but disease and patient characteristics do not significantly affect its exposure or response.
CLINICAL PHARMACOKINETICS
(2023)
Article
Oncology
Ryan D. Gentzler, Liza C. Villaruz, John C. Rhee, Bethany Horton, Joseph Mock, Michael Hanley, Kyeongmin Kim, Michelle A. Rudek, Mitch A. Phelps, Michael A. Carducci, Richard Piekarz, Kwon-Sik Park, Timothy N. Bullock, Charles M. Rudin
Summary: This study evaluated the safety of combining the HDAC inhibitor entinostat with standard of care chemotherapy and immunotherapy in patients with small cell lung cancer. The results showed that the addition of entinostat resulted in early onset and severe neutropenia and thrombocytopenia, indicating that further exploration of this combination therapy is not recommended.
Meeting Abstract
Obstetrics & Gynecology
Kara M. Rood, Marwan Ma'ayeh, Mahmoud Abdelwahab, Melanie Paglione, Nicole Abbott, Kasey Hill, Janet Guo, Kyeongmin Kim, Douglas Kniss, Mitch A. Phelps, Maged M. Costantine
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2023)
Meeting Abstract
Obstetrics & Gynecology
Jennifer L. Grasch, Chelsea Cobe, Kristen L. Benninger, Erin M. Cleary, Mitch A. Phelps, Maged M. Costantine, Kara M. Rood
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2023)
Meeting Abstract
Oncology
Ola A. Elgamal, Sandip Vibhute, Sydney Fobare, Abeera Mehmood, Mariah L. Johnson, Jean Truxall, Emily Stahl, Bridget Carmichael, Shelley J. Orwick, Ramasamy Santhanam, Kasey Hill, Susheela Tridandapani, Christopher C. Coss, Alice S. Mims, Karilyn T. Larkin, Mitch A. Phelps, Sharyn D. Baker, Alex Sparreboom, Thomas E. Goodwin, Gerard Hilinski, Chad E. Bennett, Erin Hertlein, John C. Byrd