Article
Oncology
John C. Byrd, Peter Hillmen, Paolo Ghia, Arnon P. Kater, Asher Chanan-Khan, Richard R. Furman, Susan O'Brien, Mustafa Nuri Yenerel, Arpad Illes, Neil Kay, Jose A. Garcia-Marco, Anthony Mato, Javier Pinilla-Ibarz, John F. Seymour, Stephane Lepretre, Stephan Stilgenbauer, Tadeusz Robak, Wayne Rothbaum, Raquel Izumi, Ahmed Hamdy, Priti Patel, Kara Higgins, Sophia Sohoni, Wojciech Jurczak
Summary: In this study, acalabrutinib was found to be noninferior to ibrutinib in terms of progression-free survival in patients with CLL, with a lower incidence of cardiovascular adverse events. This suggests that acalabrutinib may be a more tolerable option for continuous therapy in this patient population.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Jennifer A. Woyach, Paul M. Barr, Thomas J. Kipps, Jacqueline C. Barrientos, Inhye E. Ahn, Paolo Ghia, Vincent Girardi, Emily Hsu, Mandy Jermain, Jan A. Burger
Summary: Ibutinib has been established as a standard treatment for chronic lymphocytic leukemia, and long-term data is crucial for clinical decision-making. In the RESONATE-2 study, over half of the patients who received Ibutinib treatment for >= 5 years continued to benefit from it. Complete response rates also improved over time. Although adverse events occurred, dose modifications effectively resolved them and allowed for continued treatment.
Article
Oncology
Maria Joao Baptista, Sivasubramanian Baskar, Erika M. Gaglione, Keyvan Keyvanfar, Inhye E. Ahn, Adrian Wiestner, Clare Sun
Summary: In CLL patients, Ibrutinib treatment increases clonality of the TCR repertoire, with stable TCR clonality in patients with sustained remission and decreased TCR clonality in patients with disease progression. Additionally, T cells from responding patients show cytotoxicity against autologous CLL cells in vitro.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Francesca Romana Mauro, Diana Giannarelli, Andrea Visentin, Gianluigi Reda, Paolo Sportoletti, Anna Maria Frustaci, Annalisa Chiarenza, Stefania Ciolli, Candida Vitale, Luca Laurenti, Lorenzo De Paoli, Roberta Murru, Massimo Gentile, Gian Matteo Rigolin, Luciano Levato, Annamaria Giordano, Giovanni Del Poeta, Caterina Stelitano, Claudia Ielo, Alessandro Noto, Valerio Guarente, Stefano Molica, Marta Coscia, Alessandra Tedeschi, Gianluca Gaidano, Antonio Cuneo, Robin Foa, Maurizio Martelli, Corrado Girmenia, Giuseppe Gentile, Livio Trentin
Summary: Ibrutinib has shown superior efficacy compared to chemoimmunotherapy in the treatment of chronic lymphocytic leukemia (CLL). However, adverse events, particularly infections, are a significant concern leading to treatment discontinuation in patients receiving ibrutinib-based therapy. A large study involving 494 CLL patients treated with ibrutinib showed that approximately one-third of patients developed pneumonia or severe infections, with an overall incidence rate of 15.3% per 100 person-year. Patients with a history of severe infection, chronic obstructive pulmonary disease, or extensive prior treatment were more vulnerable to infections. The study also found that infections had a negative impact on treatment discontinuation and survival outcomes.
Article
Hematology
Adam S. Kittai, Ying Huang, Kyle A. Beckwith, Seema A. Bhat, David A. Bond, John C. Byrd, Daniel Goldstein, Michael R. Grever, Cecelia Miller, Kerry A. Rogers, Max Yano, Jennifer A. Woyach
Summary: This retrospective analysis found that progression on treatment, higher LDH levels, and lymphadenopathy without lymphocytosis were independent prognostic factors for the development of Richter's Transformation in CLL patients treated with ibrutinib. Additionally, the prognosis for Richter's Transformation remained poor.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Immunology
Yanyan Liu, Yongping Song, Qingsong Yin
Summary: This review summarizes the effects of ibrutinib on the tumor microenvironment and cellular immunity in patients with CLL, particularly focusing on the behavior and function of T cells. The potential mechanisms of ibrutinib are explored, providing a basis for the clinical benefits of long-term ibrutinib treatment and combined therapy based on T-cell-based immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Max J. Gordon, Jade E. Jones, Binsah George, Christine Peterson, Jan A. Burger, Nitin Jain, Michael Keating, William G. Wierda, Jean-Bernard Durand, Alessandra Ferrajoli
Summary: This study reports the 5-year follow-up results of patients with CLL who received treatment with ibrutinib, focusing on hypertension and cardiovascular toxicities. The findings showed that although hypertension is a common side effect, it is manageable in most patients, and baseline cardiovascular disease does not affect ibrutinib-related hypertension nor is hypertension associated with major adverse cardiovascular events or survival.
Article
Hematology
John F. Seymour, John C. Byrd, Paolo Ghia, Arnon P. Kater, Asher Chanan-Khan, Richard R. Furman, Susan O'Brien, Jennifer R. Brown, Talha Munir, Anthony Mato, Stephan Stilgenbauer, Naghmana Bajwa, Paulo Miranda, Kara Higgins, Ellie John, Marianne de Borja, Wojciech Jurczak, Jennifer A. Woyach
Summary: ELEVATE-RR trial showed that acalabrutinib has noninferior progression-free survival and lower incidence of key adverse events compared to ibrutinib in previously treated chronic lymphocytic leukemia patients. Post hoc analysis further characterized the adverse events of acalabrutinib and ibrutinib. It was found that acalabrutinib had higher incidence rates of headache and cough, while ibrutinib had higher rates of diarrhea, joint pain, urinary tract infection, back pain, muscle spasms, and dyspepsia. Ibrutinib also had higher rates of atrial fibrillation/flutter, hypertension, and bleeding. The discontinuation rate due to adverse events was lower with acalabrutinib. The overall event-based analyses and adverse event burden scores demonstrated that ibrutinib had a higher burden of adverse events compared to acalabrutinib, particularly in atrial fibrillation, hypertension, and bleeding.
Article
Hematology
Paul M. Barr, Carolyn Owen, Tadeusz Robak, Alessandra Tedeschi, Osnat Bairey, Jan A. Burger, Peter Hillmen, Steve E. Coutre, Claire Dearden, Sebastian Grosicki, Helen McCarthy, Jian-Yong Li, Fritz Offner, Carol Moreno, Cathy Zhou, Emily Hsu, Anita Szoke, Thomas J. Kipps, Paolo Ghia
Summary: This study reports long-term follow-up data from the RESONATE-2 phase 3 study of ibrutinib in previously untreated CLL patients. The results show that ibrutinib provides sustained benefit in terms of progression-free survival and overall survival, even in patients with high-risk genomic features.
Article
Oncology
Christian Brieghel, Kathrine Aarup, Mathias H. Torp, Michael A. Andersen, Christina W. Yde, Xin Tian, Adrian Wiestner, Inhye E. Ahn, Carsten U. Niemann
Summary: In chronic lymphocytic leukemia (CLL), patients with multi-hit TP53 aberrations have poorer overall survival, progression-free survival, and time-to-progression compared to those with single-hit TP53, while single-hit TP53 defines a distinct subgroup of patients with excellent response to single-agent ibrutinib. These findings highlight the importance of further investigation into prognostication and management of multi-hit TP53 CLL.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Inhye E. Ahn, Xin Tian, David Ipe, Mei Cheng, Maher Albitar, L. Claire Tsao, Lei Zhang, Wanlong Ma, Sarah E. M. Herman, Erika M. Gaglione, Susan Soto, James P. Dean, Adrian Wiestner
Summary: This study aimed to establish a prognostic model to stratify patients into high, intermediate, and low-risk groups. The study identified TP53 aberration, prior treatment, beta-2 microglobulin level, and lactate dehydrogenase level as independent factors associated with progression-free survival and overall survival. The model was validated in internal and external validation cohorts.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Hematology
Lindsey E. Roeker, Maral DerSarkissian, Kellie Ryan, Yan Chen, Mei Sheng Duh, Svea K. Wahlstrom, Shweta Hakre, Louise Yu, Helen Guo, Anthony R. Mato
Summary: Acalabrutinib demonstrated lower rates of treatment discontinuation and a prolonged time to discontinuation compared to ibrutinib in patients with CLL.
Article
Oncology
Maria Cristina Puzzolo, Ilaria Del Giudice, Nadia Peragine, Paola Mariglia, Maria Stefania De Propris, Luca Vincenzo Cappelli, Livio Trentin, Gianluigi Reda, Antonio Cuneo, Stefano Molica, Alfonso Piciocchi, Valentina Arena, Francesca Romana Mauro, Anna Guarini, Robin Foa
Summary: Research suggests that ibrutinib treatment can reverse T-cell polarization in chronic lymphocytic leukemia (CLL), decreasing Th2 cells and increasing Th1 cells, with a gradual reduction in the Th2/Th1 ratio after treatment initiation. Furthermore, patients with a Th2/Th1 ratio below 0.088 at M8 are more likely to achieve complete remission (CR).
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Fuli Fan, Hyeon Joo Yoo, Sophia Stock, Lei Wang, Yibin Liu, Maria-Luisa Schubert, Sanmei Wang, Brigitte Neuber, Angela Hueckelhoven-Krauss, Ulrike Gern, Anita Schmitt, Carsten Mueller-Tidow, Peter Dreger, Michael Schmitt, Leopold Sellner
Summary: The use of ibrutinib has been shown to improve the viability and expansion of CART cells derived from CLL patients, enriching them with less-differentiated naive-like T cell subsets and reducing exhaustion marker expression. Additionally, ibrutinib enhances the cytokine release capacity of CLL patient-derived CART cells, suggesting it can improve the yield and function of these cell products.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Paul J. Hampel, Kari G. Rabe, Timothy G. Call, Wei Ding, Jose F. Leis, Asher A. Chanan-Khan, Saad S. Kenderian, Eli Muchtar, Yucai Wang, Sikander Ailawadhi, Amber B. Koehler, Ricardo Parrondo, Susan M. Schwager, Taimur Sher, Curtis A. Hanson, Min Shi, Daniel L. Van Dyke, Esteban Braggio, Susan L. Slager, Neil E. Kay, Sameer A. Parikh
Summary: Patients with chronic lymphocytic leukemia (CLL) who have disease progression on ibrutinib have worse outcomes compared to those who stop ibrutinib due to toxicity. A study evaluated the outcomes of CLL patients with disease progression on ibrutinib and found that overall survival (OS) was longer for patients who received ibrutinib as a frontline treatment and next-line treatments such as chimeric antigen receptor T-cell therapy and venetoclax-based treatment showed better outcomes compared to other approved treatments. These findings suggest a need for better treatment options for CLL patients with disease progression on ibrutinib.
BLOOD CANCER JOURNAL
(2022)
