Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Chatzikonstantinou, Thomas; Scarfò, Lydia; Karakatsoulis, Georgios; Minga, Eva; Chamou, Dimitra; Iacoboni, Gloria; Kotaskova, Jana; Demosthenous, Christos; Smolej, Lukas; Mulligan, Stephen; Alcoceba, Miguel; Al-Shemari, Salem; Aurran-Schleinitz, Thérèse; Bacchiarri, Francesca; Bellido, Mar; Bijou, Fontanet; Calleja, Anne; Medina, Angeles; Khan, Mehreen Ali; Cassin, Ramona; Chatzileontiadou, Sofia; Collado, Rosa; Christian, Amy; Davis, Zadie; Dimou, Maria; Donaldson, David; Santos, Gimena Dos; Dreta, Barbara; Efstathopoulou, Maria; El-Ashwah, Shaimaa; Enrico, Alicia; Fresa, Alberto; Galimberti, Sara; Galitzia, Andrea; García-Serra, Rocío; Gimeno, Eva; González-Gascón-y-Marín, Isabel; Gozzetti, Alessandro; Guarente, Valerio; Guieze, Romain; Gogia, Ajay; Gupta, Ritu; Harrop, Sean; Hatzimichael, Eleftheria; Herishanu, Yair; Hernández-Rivas, José-Ángel; Inchiappa, Luca; Jaksic, Ozren; Janssen, Susanne; Kalicińska, Elżbieta; Laribi, Kamel; Karakus, Volkan; Kater, Arnon P.; Kho, Bonnie; Kislova, Maria; Konstantinou, Eliana; Koren-Michowitz, Maya; Kotsianidis, Ioannis; Kreitman, Robert J.; Labrador, Jorge; Lad, Deepesh; Levin, Mark-David; Levy, Ilana; Longval, Thomas; Lopez-Garcia, Alberto; Marquet, Juan; Martin-Rodríguez, Lucia; Maynadié, Marc; Maslejova, Stanislava; Mayor-Bastida, Carlota; Mihaljevic, Biljana; Milosevic, Ivana; Miras, Fatima; Moia, Riccardo; Morawska, Marta; Murru, Roberta; Nath, Uttam Kumar; Navarro-Bailón, Almudena; Oliveira, Ana C.; Olivieri, Jacopo; Oscier, David; Panovska-Stavridis, Irina; Papaioannou, Maria; Papajík, Tomas; Kubova, Zuzana; Phumphukhieo, Punyarat; Pierie, Cheyenne; Puiggros, Anna; Rani, Lata; Reda, Gianluigi; Rigolin, Gian Matteo; Ruchlemer, Rosa; Daniel de Deus Santos, Marcos; Schipani, Mattia; Schiwitza, Annett; Shen, Yandong; Simkovic, Martin; Smirnova, Svetlana; Abdelrahman Soliman, Dina Sameh; Spacek, Martin; Tadmor, Tamar; Tomic, Kristina; Tse, Eric; Vassilakopoulos, Theodoros; Visentin, Andrea; Vitale, Candida; von Tresckow, Julia; Vrachiolias, George; Vukovic, Vojin; Walewska, Renata; Wasik-Szczepanek, Ewa; Xu, Zhenshu; Yagci, Munci; Yañez, Lucrecia; Yassin, Mohamed; Zuchnicka, Jana; Angelopoulou, Maria; Antic, Darko; Biderman, Bella; Catherwood, Mark; Claus, Rainer; Coscia, Marta; Cuneo, Antonio; Demirkan, Fatih; Espinet, Blanca; Gaidano, Gianluca; Kalashnikova, Olga B.; Laurenti, Luca; Nikitin, Eugene; Pangalis, Gerassimos A.; Panagiotidis, Panagiotis; Popov, Viola Maria; Pospisilova, Sarka; Sportoletti, Paolo; Stavroyianni, Niki; Tam, Constantine; Trentin, Livio; Chatzidimitriou, Anastasia; Bosch, Francesc; Doubek, Michael; Ghia, Paolo; Stamatopoulos, Kostas

doi:10.1016/j.eclinm.2023.102307

Cited by 7 publications

(3 citation statements)

References 44 publications

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“…Notably, these patients exhibited a lower OS, particularly those diagnosed with AML or MDS. Finally, data confirmed that the occurrence of AML or MDS was specifically associated with the administration of the FC ± R regimen [ 235 ].…”

Section: Secondary Primary Malignanciesmentioning

confidence: 67%

Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents

Galitzia,

Maccaferri,

Mauro

et al. 2024

Cancers

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The treatment landscape for CLL has undergone a profound transformation with the advent of targeted agents (TAs) like Bruton’s Tyrosine Kinase inhibitors (BTKis) and BCL-2 inhibitors (BCL-2is). These agents target crucial cellular pathways in CLL, offering superior efficacy over traditional chemo-immunotherapy, which has led to improved progression-free and overall survival rates. This advancement promises enhanced disease control and potentially normal life expectancy for many patients. However, the journey is not without challenges, as these TAs are associated with a range of adverse events (AEs) that can impact treatment efficacy and patient quality of life. This review focuses on detailing the various AEs related to TA management in CLL, evaluating their frequency and clinical impact. The aim is to present a comprehensive guide to the effective management of these AEs, ensuring optimal tolerability and efficacy of TAs. By reviewing the existing literature and consolidating findings, we provide insights into AE management, which is crucial for maximizing patient outcomes in CLL therapy.

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Section: Secondary Primary Malignanciesmentioning

confidence: 67%

Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents

Galitzia,

Maccaferri,

Mauro

et al. 2024

Cancers

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“…The clinical heterogeneity that characterizes CLL is largely due to the age at the start of treatment and to the wide spectrum of comorbidities in patients, ranging from young and fit patients to very elderly patients suffering from several other diseases, as well as the variability of genetic aberrations within CLL cells [66][67][68]. TP53 abn, IGHV gene mutational status and karyotype represent the main prognostic factors of CLL [9,69,70].…”

Section: Discussionmentioning

confidence: 99%

Innovative Combinations, Cellular Therapies and Bispecific Antibodies for Chronic Lymphocytic Leukemia: A Narrative Review

Visentin,

Frazzetto,

Trentin

et al. 2024

Cancers

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In the last few years, several agents targeting molecules that sustain the survival and the proliferation of chronic lymphocytic leukemia (CLL) cells have become clinically available. Most of these drugs target surface proteins, such as CD19 or CD20, via monoclonal or bispecific monoclonal antibodies (BsAbs), CAR T cells, intracellular proteins like BTK by using covalent or non-covalent inhibitors or BCL2 with first or second generation BH3-mimetics. Since the management of CLL is evolving quickly, in this review we highlighted the most important innovative treatments including novel double and triple combination therapies, CAR T cells and BsAbs for CLL. Recently, a large number of studies on novel combinations and newer strategic options for CLL therapy have been published or presented at international conferences, which were summarized and linked together. Although the management of treatment with a single continuous agent is easier, the emergence of protein mutations, long-term toxicities and costs are important concerns that favor the use of a fixed duration therapy. In the future, a measurable residual disease (MRD)-guided treatment cessation and MRD-based re-initiation of targeted therapy seems to be a more feasible approach, allowing identification of the patients who might benefit from continuous therapy or who might need a consolidation with BsAbs or CAR T cells to clear the neoplastic clone.

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“…Although lacking key attributes of RCTs, real‐world studies can include large cohorts of patients with long follow‐ups and better portray the reality of everyday clinical practice. To this point, real‐world studies have revealed the clinical importance of several biomarkers in CLL (e.g., CK and BcR stereotypy), helped us understand the adherence to guidelines in terms of biomarker testing, and gave insights into long‐term complications 42,110–112 . In the era of targeted agents, RWE gave us insights into the tolerability and effectiveness of these drugs while also revealing the unmet need for effective treatments in patients relapsing after receiving both BTKi and venetoclax‐based treatments 113,114 …”

Section: Rwd Aggregationmentioning

confidence: 99%

Realizing precision medicine in chronic lymphocytic leukemia: Remaining challenges and potential opportunities

Stamatopoulos,

Pavlova,

Al‐Sawaf

et al. 2024

HemaSphere

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Patients with chronic lymphocytic leukemia (CLL) exhibit diverse clinical outcomes. An expanding array of genetic tests is now employed to facilitate the identification of patients with high‐risk disease and inform treatment decisions. These tests encompass molecular cytogenetic analysis, focusing on recurrent chromosomal alterations, particularly del(17p). Additionally, sequencing is utilized to identify TP53 mutations and to determine the somatic hypermutation status of the immunoglobulin heavy variable gene. Concurrently, a swift advancement of targeted treatment has led to the implementation of novel strategies for patients with CLL, including kinase and BCL2 inhibitors. This review explores both current and emerging diagnostic tests aimed at identifying high‐risk patients who should benefit from targeted therapies. We outline existing treatment paradigms, emphasizing the importance of matching the right treatment to the right patient beyond genetic stratification, considering the crucial balance between safety and efficacy. We also take into consideration the practical and logistical issues when choosing a management strategy for each individual patient. Furthermore, we delve into the mechanisms underlying therapy resistance and stress the relevance of monitoring measurable residual disease to guide treatment decisions. Finally, we underscore the necessity of aggregating real‐world data, adopting a global perspective, and ensuring patient engagement. Taken together, we argue that precision medicine is not the mere application of precision diagnostics and accessibility of precision therapies in CLL but encompasses various aspects of the patient journey (e.g., lifestyle exposures and comorbidities) and their preferences toward achieving true personalized medicine for patients with CLL.

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Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Cited by 7 publications

References 44 publications

Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents

Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents

Innovative Combinations, Cellular Therapies and Bispecific Antibodies for Chronic Lymphocytic Leukemia: A Narrative Review

Realizing precision medicine in chronic lymphocytic leukemia: Remaining challenges and potential opportunities

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