Chronic Lymphocytic Leukemia Care and Beyond: Navigating the Needs of Long-Term Survivors

Cancers, Journal Year: 2025, Volume and Issue: 17(1), P. 119 - 119

Published: Jan. 2, 2025

Chronic lymphocytic leukemia (CLL) treatment has undergone a significant evolution with shift from historical chemotherapeutic regimens to targeted therapies such as Bruton tyrosine kinase (BTK) and BCL-2 inhibitors. These advancements have been associated notable improvement in survival rates transformation of CLL into chronic manageable condition for most persons this disease. However, consequence improved outcomes, long-term survivors now face emergent challenges which include risk infections, cardiovascular complications, secondary malignancies. In changed scenario, holistic models care are essential address health risks. Such patients require multidisciplinary approach that integrates the proactive management frailty, comorbidities, psychosocial well-being enhance both quality life (QoL). predominantly affects older persons, many whom present concurrent frailty comorbidities may complicate impact QoL. Comprehensive geriatric assessments (GA) play critical role identification at heightened treatment-related toxicity help guide rational therapy selection, particularly very frail persons. addition assessment hematological responses, prospective patient-reported outcomes (PROs) metrics offer more nuanced understanding global benefits. A survivorship-focused model is crucial multifaceted needs extension patient broader domain maintenance improvements

Language: Английский

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A 3-week pause versus continued Bruton tyrosine kinase inhibitor use during COVID-19 vaccination in individuals with chronic lymphocytic leukaemia (IMPROVE trial): a randomised, open-label, superiority trial

The Lancet Haematology, Journal Year: 2025, Volume and Issue: 12(4), P. e294 - e303

Published: April 1, 2025

Language: Английский

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Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach

Diseases, Journal Year: 2024, Volume and Issue: 12(5), P. 95 - 95

Published: May 6, 2024

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, outcomes persistent COVID-19 symptoms in encompassing vulnerable populations, such as pregnant women oncological patients. Our objective is to emphasize critical significance adopting an integrated approach for early detection appropriate management long COVID. The incidence severity can significant impact on quality life patients course disease case pre-existing pathologies. Particularly, fragile patients, presence PASC related significantly worse survival, independent from vulnerabilities treatment. It important try achieve recognition management. Various mechanisms are implicated, resulting wide range presentations. Understanding specific factors involved crucial tailoring effective interventions support strategies. Management approaches involve biopsychosocial assessments treatment comorbidities, autonomic dysfunction, well multidisciplinary rehabilitation. overall one gradual improvement, with recovery observed majority, though not all, As research long-COVID continues evolve, ongoing studies likely shed more light intricate relationship between chronic diseases, status, cardiovascular psychiatric disorders, effects This information could guide healthcare providers, researchers, policymakers developing targeted interventions.

Language: Английский

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Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS‐CoV‐2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL

American Journal of Hematology, Journal Year: 2024, Volume and Issue: 99(4), P. 745 - 750

Published: Jan. 24, 2024

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination anti-Spike specific antibodies. Booster doses increased seroconversion rate antibody titers in all patient categories, ultimately generating similar those observed postinfection cohort. In detail, overscale median arose >80% watch wait, off-therapy remission, under treatment venetoclax single-agent. Anti-CD20 antibodies active BTK inhibitors (BTKi) represent limiting factors response, still mounted ~40% cases following (Blue) Evaluation SARS-CoV-2-specific responses. Number functional activation markers documented each patient. The vast majority patients, including seronegative, developed responses, qualitatively between groups alone infection cases. These data highlight efficacy eliciting immunity independently status support use additional boosters stimulate on CLL-directed treatments. past 3 years, (severe acute respiratory syndrome coronavirus-2) leading coronavirus disease 2019 (COVID-19) has threatened life (CLL). Though declining over time thanks effective interventions, case fatality percentage CLL experiencing infections remained higher than general population.1 This vulnerability is unsurprising, considering that per se associated a characteristic dysfunction,2 therapies may further worsen suppression. Factors infectious have been also an COVID-19 vaccines.3, 4 To some extent, immunogenicity CLL,5, 6 though dynamics cellular remain controversial. Indeed, studies suggested T cells be generated anti-CLL therapies,7-9 while others indicated certain degree immunity,10 mostly seen treatment.11 Besides, potential differences from natural by thoroughly assessed. this work, large multicenter study coordinated ERIC (Table S1), we prospectively collected concerning cohort 596 diagnosed CLL, well-annotated for type anti-leukemic therapy S2). Within cohort, investigated primary 2-dose cycle 533 (Figure S1). confirmed suboptimal CLL. more rates were statistically both remission (79%; 48/61) naïve (watch wait) (65%; 123/189) comparison single-agent Bruton tyrosine kinase (26%; 50/194) combination BTKi (8%; 1/12) exposed anti-CD20 <12 months before (12%; 5/41) 1A). Notably, among actively treated receiving as achieved significantly (55%; 10/18) Antibody concentrations showed trend; presented highest titer (585 U/mL), lowest (22.6 U/mL, p < .01) Among numerically major subgroups, identified univariate analysis characteristics rate. unmutated immunoglobulin heavy variable genes (u-IGHV) lower, deletion(13q) Deletion(17q) had negative impact BTKi. serum deficiency (IgG≤6g/dL) paralleled low S3). Then, analyzed 268 first S1 Table Although showing post-2 assessment, only 47% (52/112) BTKi, 27% (3/11) plus 32% (6/19) exhibited At variance, wait positive 100% (22/22) 85% (73/86) cases, respectively, above upper limit quantification (>2500 U/mL) presence u-IGHV negatively impacted whereas trisomy chromosome 12 mutation TP53 gene did so Focusing who failed achieve two available (N = 118) 95) treated. Of these 28% (20/71) 33% (3/9) venetoclax, 14% (2/14) seroconverted Last, evaluated, 76 effect mRNA second Only 40% (14/35) seropositive, (33 Both (80% 4/5;) (2500 (86%; 24/28) (100%; 6/6) 1A), although small numbers preclude drawing definitive conclusions. persistently seronegative third followed longitudinally, fourth elicited 21% (4/19) very (median 1.34 66 4–16 weeks sampling S1); but four received least Infection induced (85%; 11/13) clinical (80%; 4/5) none (0/3) infused anti-CD20, 66% (22/33) 50% (3/6) detectable antibodies, (6/6) Median rates, being subgroups (105 U/mL; 59 previously additionally evaluated S1) through established assay monitors expression multiple (n 7), surface IL-2, IFN-γ, TNF-α secretion spike peptides12 S4 Figure All spike-specific activation. particular, 92% (54/59) 68% (40/59) one marker CD4+ CD8+ cells, respectively 1B). parallel, considered co-expression dissect quality response. 30 n 5 venetoclax) frequencies untreated 10 remission) 1B S3 Graphical Abstract). No influenced S5). 27 post-only-vaccination cell 23/27) Moreover, vaccinated pattern patients. Also category, not no significant when stratified respective counterparts, thus excluding biases deriving few present Importantly, (12/13) terms comparable whole group summary, report treatment-naïve measurable scale, increasing up dose, indicated.6 line previous anti-S1-immunoglobulin concentration correlates neutralizing capacity hematologic malignancies,13 our can develop Whether immunization might against emerging novel variants remains tested. able delve deeper into show ongoing monoclonal treatments beyond cycle. Having said that, increase titers, BTKi-treated lower extent suggesting appropriateness administering even successfully it great interest evident detrimental association emerged treatments, variance potentially reflective universal if how indeed correlate actual protection end, compare occurs magnitude post-booster confirming factor developing post-infected individuals. That notwithstanding, remarkable independent Future research needed establish level sufficient protect deadly consequences high context, prompt especially regardless their status. said, advisable optimize timing start order shorten (and number boosters) memory: during follow-up, either therapy, best setting where promptly administer vaccines. ACam, ACap, PG, KS, LS designed study, data, wrote manuscript. SH, CT, MF, PR, EP, MK, ML performed analyses data. EA, FM, ES, MC, CC, YH, TC, MD, KG, MS, CM, MM, HB, SA, SL, APK, MH, ISN, QH, CD, JK, JZ, FV, AMR, DB, IET, VMP, VR, NS, ES samples provided project was supported part Fondazione Veronesi (ID 1852164), Janssen (IBR-I-20-EMEA-014-V01/54179060CLL4024; NOPRODCLL4001), MH CZ—DRO (FNBr, 65269705) AIRC mille program 2018 21198). [Correction added February 21, 2024, online publication: preceding sentence, statistical significance (single-agent) 1 paragraph corrected.] YH: honoraria Janssen, AbbVie, AstraZeneca, Meidson, Lilly, Roche; grant Janssen. TC: AbbVie. HB: Abbvie, Astra Zeneca, Alvogen, Astellas, Amgen, Bristol Meyers Squibb, Novartis, Pfizer, Roche, Sobi, Sandoz, Swixx, Takeda. MD: advisory boards AOP Orphan, Glaxo-Smith-Kline. MS: travel grants AstraZeneca. NS: LS: BeiGene, speakers bureau Octapharma. KS: Janssen; Gilead Sciences, Roche. PG: Arqule/MSD, Celgene/Juno/BMS, Loxo/Lilly, Gilead, Sunesis. other authors declare conflicts interest. findings are request corresponding author. publicly due privacy ethical restrictions. Data S1. Supporting Information. Please note: publisher responsible content functionality any supporting information supplied authors. Any queries (other missing content) should directed author article.

Language: Английский

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Awareness and Knowledge About Preventive Vaccinations Among Patients with Hematological Malignancies

Vaccines, Journal Year: 2025, Volume and Issue: 13(3), P. 284 - 284

Published: March 7, 2025

Background: Patients with hematological malignancies, including multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), are at an increased risk of severe infections due to both disease- therapy-related immunosuppression. This cross-sectional study evaluated awareness infection risks vaccination uptake among 150 adults various malignancies from major Polish centers. Methods: All participants completed a 30-item questionnaire capturing demographic data, treatment history, frequency, attitude. Statistical analyses utilized Chi-square Fisher’s exact tests, p < 0.05 considered statistically significant. Results: Respondents had median age 57 years (range, 30–79), 65.3% were female. MM was the most common diagnosis (64.7%), followed by CLL (4.0%) other (31.3%). Nearly all (99.3%) acknowledged their susceptibility infections. Frequent (≥2 in past 6 months) significantly associated transfusion dependency (p = 0.0001) history hematopoietic stem cell transplantation (HSCT, 0.009). Although 69.3% expressed willingness be vaccinated, 23.3% declined COVID-19 insufficient cancer-specific safety data. Higher education urban residence correlated greater acceptance vaccines 0.05). Conclusions: Our findings underscore critical need for targeted educational strategies robust guidelines this immunocompromised population. Enhanced patient timely implementation tailored regimens could reduce infection-related morbidity improve tolerability cancer treatments.

Language: Английский

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

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1290 - 1290

Published: March 26, 2024

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

Language: Английский

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

Cancers, Journal Year: 2024, Volume and Issue: 16(11), P. 1996 - 1996

Published: May 24, 2024

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

Language: Английский

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Risk of SARS-CoV-2 infection and severe COVID-19 in hematological patients who received or not pre-exposure prophylaxis with tixagevimab/cilgavimab: a target trial emulation

Leukemia & lymphoma/Leukemia and lymphoma, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 8

Published: June 4, 2024

We emulated a hypothetical target trial in which hematological subjects cared at the University Hospital of Pisa (Italy) received or not SARS-CoV-2 prophylaxis with tixagevimab/cilgavimab. Subjects who (cases) were compared to those did (controls). The main outcome was infection subsequent 6 months. Inverse probability weighting (IPW) used adjust for confounders. A multivariable analysis performed identify variables associated infection. recruited 462 patients: 228 prophylaxis, 234 controls. COVID-19 lower cases controls (16.7% vs 24.8%, p = 0.03, after IPW 14.3% 24.6%, 0.01). On analysis, B-cell depleting therapies (HR 2.09, 95%CI 1.05-4.18, 0.037) increased risk COVID-19, while tixagevimab/cilgavimab 0.45, 0.27-0.73, 0.001) and previous 0.27, 0.14-0.51, < protective. In conclusion, monoclonal antibodies may reduce patients.

Language: Английский

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Severe infections in patients with chronic lymphocytic leukemia included in trials investigating BTK and BCL2 inhibitors

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 201, P. 104408 - 104408

Published: June 15, 2024

Language: Английский

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

HemaSphere, Journal Year: 2024, Volume and Issue: 8(7)

Published: July 1, 2024

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

Language: Английский

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