A simplified prognostic index for chronic lymphocytic leukemia treated with ibrutinib: Results from a multicenter retrospective cohort study

Gordon, Max J.; Sitlinger, Andrea; Salous, Tareq; Alqahtani, Hamood; Churnetski, Michael C.; Rivera, Xavier; Wisniewski, Paul; Cohen, Jonathon B.; Patel, Krish; Shadman, Mazyar; Choi, Michael Y.; Hill, Brian T.; Stephens, Deborah M.; Persky, Daniel O.; Brander, Danielle M.; Danilov, Alexey V.

doi:10.1016/j.leukres.2020.106302

“…Notably, del(17p) has been suggested to be a poor prognostic factor in patients who receive frontline ibrutinib with no negative impact of del(17p) on OS in the R/R setting, while R/R disease, age, performance status, and comorbidities were reported as determinants of poor OS in ibrutinib-treated patients with CLL [ 41 ]. Moreover, the frequency of high-risk genomic abnormalities including del(17p) has been suggested to dramatically increase with increasing lines of chemotherapy, and treatment with single-agent ibrutinib earlier in the disease course before the development of these abnormalities has therefore been considered to improve patient outcomes [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Tombak

¹

,

Tanrıkulu

²

,

Durusoy

³

et al. 2021

Tjh

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Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.

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“…Ibrutinib has improved outcomes in CLL to an extent that many prognostic markers and risk-scores relevant in the CIT era are no longer applicable or need to be revised. 41 – 44 …”

Section: How Ibrutinib Became Standard Of Care In De Novo mentioning

confidence: 99%

“…Ibrutinib has improved outcomes in CLL to an extent that many prognostic markers and riskscores relevant in the CIT era are no longer applicable or need to be revised. [41][42][43][44] Something new: second generation BTK inhibitors, does selectivity improve outcomes? Adverse events leading to ibrutinib discontinuation have emerged as an obstacle to indefinite therapy, 45 and it is perceived that the second generation BTK inhibitors may be better tolerated.…”

mentioning

confidence: 99%

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The evolving role of Bruton’s tyrosine kinase inhibitors in chronic lymphocytic leukemia

Gordon

¹

,

Danilov

²

2021

Therapeutic Advances in Hematology

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Ibrutinib, the first in class of the oral covalent Bruton tyrosine kinase (BTK) inhibitors, has profoundly changed the treatment landscape of chronic lymphocytic leukemia (CLL). The phase III RESONATE and RESONATE-2 trials first demonstrated the superiority of ibrutinib over ofatumumab in the relapsed/refractory setting and over chlorambucil in older patients with de novo disease. The phase III ECOG–ACRIN trial extended these results to young, fit patients, demonstrating a significant survival advantage to ibrutinib plus rituximab over fludarabine, cyclophosphamide, and rituximab. Similarly, the Alliance trial demonstrated the superiority of ibrutinib over bendamustine with rituximab as frontline in elderly patients. Challenges with ibrutinib include toxicity, development of resistance, and need for indefinite therapy. The second generation BTK inhibitor acalabrutinib may cause less off-target toxicity. The ELEVATE TN trial demonstrated the superiority of acalabrutinib with or without obinutuzumab over chlorambucil and obinutuzumab as frontline therapy for elderly or comorbid patients. Promising early results from the phase II CAPTIVATE and CLARITY trials, which combined ibrutinib with venetoclax, suggest a future role for minimal residual disease (MRD) testing to determine treatment duration. The ongoing phase III GAIA/CLL13, ECOG EA9161, Alliance A041702, CLL17, and [ClinicalTrials.gov identifier: NCT03836261] trials will assess various combinations of ibrutinib/acalabrutinib, venetoclax, and anti-CD20 antibodies. These trials will answer key questions in the treatment of CLL: should novel agents in CLL be used in combination or sequentially? What is the best frontline agent? Can treatment be safely stopped with BTK inhibitors? Can undetectable MRD be used to determine treatment duration? In this review, we will discuss these and other aspects of the evolving role of BTK inhibition in CLL.

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“…Saját betegeink között a PFS szignifi kancia határon lévő csökkenését tapasztaltuk emelkedett RDW-szint esetén. Ibrutinibkezeléssel kapcsolatban Gordon és mtsai a 70 év feletti életkort, a refrakter/relabált (R/R) betegséget és a >6 CIRS komorbiditási indexből képzett magasabb pontszámot prognosztikus indexként ajánlották az ibrutinibbel kezelt CLL-es betegek eseménymentes és teljes túlélésének előrejelzésére [33]. Egyéb irodalmi adatokkal összhangban a CR elérése az egyéb vizsgált tényezőktől független, szignifi káns hatással bír a betegek progressziómentes túlélésére.…”

Section: Eredeti Közleményunclassified

A progressziómentes túlélést befolyásoló tényezők vizsgálata ibrutinibbel kezelt krónikus lymphoid leukémiás betegekben

Szerafin

¹

,

Takacs

²

,

Varjasi

³

et al. 2021

Hematológia–Transzfuziológia

0

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Összefoglaló. Bevezetés: A krónikus lymphoid leukémia kezelésében jelentős előrelépést eredményezett az ibrutinibterápia bevezetése. A gyógyszer első vonalbeli és többed vonalbeli kezelése is magas remissziós arányt eredményezett, bár a terápia korai bevezetése és a kedvező genetikai eltérések esetén az eredmények jobbak. A progressziómentes túlélést befolyásoló egyéb tényezőkről azonban még kevés adat áll rendelkezésre. Célkitűzés: Krónikus lymphoid leukémiás betegek ibrutinibkezelése során a teljes hematológiai remisszió elérését és a progressziómentes túlélés időtartamát befolyásoló tényezők vizsgálata. Betegek és módszer: 47 krónikus lymphoid leukémiás beteg (életkor: 39–84 év, férfi 27, nő 20, követési idő 5–58 hónap, medián 15 hónap) klinikai és laboratóriumi adatainak retrospektív elemzése. Eredmények: A teljes hematológiai remisszió elérése független volt a betegek nemétől, életkorától, a betegség stádiumától, az immunglobulin gén nehézlánc-variábilis régió státuszától, a genetikai aberrációktól, az abszolút neutrophilszámtól, az abszolút monocytaszámtól és a vörösvértestnagyság-eloszlási görbe szélességétől. A progressziómentes túlélést a komplett remisszió elérése (p = 0,00073) és a magasabb abszolút neutrophilszám (<4 G/l vs. ≥4 G/l, p = 0,022) befolyásolta szignifikánsan, a vörösvértestnagyság-eloszlási görbe szélességértékével való összefüggés pedig statisztikailag határértéken volt (p = 0,065). A Cox-féle regressziós elemzésbe bevont változók közül csak a teljes hematológiai remisszió elérése mutatott szignifikáns hatást a progressziómentes túlélésre (p = 0,0147). Következtetések: A teljes hematológiai remisszió elérése az egyéb vizsgált tényezőktől független, szignifikáns hatással bír a betegek progressziómentes túlélésére. Az abszolút neutrophilszám és a vörösvértestnagyság-eloszlási görbe szélessége szintén hasznos kiegészítő prognosztikus marker lehet. Az elemzett esetek száma még alacsony a komolyabb következtetések levonására, azonban így is elmondható, hogy az eredmények egy része már a szakirodalom korábbi eredményeit tükrözi. Summary. Introduction: The introduction of ibrutinib therapy has led to significant advances in the treatment of chronic lymphocytic leukemia. Both first-line and multiple-lines treatments of the drug resulted in high remission rates, although results were better with early initiation of therapy and favorable genetic abnormalities. However, little data are available on other factors influencing progression-free survival. Objective: To investigate factors influencing the achievement of complete hematological remission and progression-free survival with ibrutinib treatment in patients with chronic lymphocytic leukemia. Patients and metods: Retrospective analysis of clinical and laboratory data from 47 chronic lymphoid leukemia patients (age: 39–84 years, male 27, female 20, follow-up 5–58 months, median 15 months). Results: Achieving complete hematologic remission was independent of patient gender, age, disease stage, immunoglobulin heavy chain variable region status, genetic aberrations, absolute neutrophil count, absolute monocyte count, and red blood cell distribution width. Progression-free survival was significantly affected by complete remission (p = 0.00073), and higher absolute neutrophil counts (<4 G/l vs. ≥ 4 G/l, p = 0.022), the red blood cell distribution width was statistically less significant (p = 0.065). Of the variables included in the Cox regression analysis, only the achievement of complete hematologic remission had a significant effect on progression-free survival (p = 0.0147). Conclusions: Achieving complete hematologic remission, independent of the other factors studied, has a significant effect on patients’ progression-free survival. Absolute neutrophil count and red blood cell distribution width can also be a useful additional prognostic marker. The number of analyzed cases is still low to draw more serious conclusions, but it can still be said that some of the results already reflect previous results in the literature.

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A simplified prognostic index for chronic lymphocytic leukemia treated with ibrutinib: Results from a multicenter retrospective cohort study

Cited by 5 publications

References 13 publications

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

The evolving role of Bruton’s tyrosine kinase inhibitors in chronic lymphocytic leukemia

A progressziómentes túlélést befolyásoló tényezők vizsgálata ibrutinibbel kezelt krónikus lymphoid leukémiás betegekben

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