The Treatment of Relapsed Refractory Chronic Lymphocytic Leukemia

Brown, Jennifer R.

doi:10.1182/asheducation-2011.1.110

Cited by 40 publications

(31 citation statements)

References 67 publications

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“…1 CLL has a widely variable disease course: some patients have indolent disease not requiring treatment for decades, whereas others have aggressive disease requiring immediate treatment. 1,2 Although oral alkylating agents like chlorambucil were historically the initial standard therapy for patients with CLL/small lymphocytic lymphoma (SLL), 3 newer agents such as fludarabine, with or without cyclophosphamide, [4][5][6] and bendamustine 7 have improved response rates and remission durations. Furthermore, as demonstrated by the German CLL Study Group CLL8 trial, the addition of rituximab to fludarabine and cyclophosphamide (FCR) improved not just progression-free survival (PFS) but also overall survival, establishing chemoimmunotherapy (CIT) as the standard of care for firstline treatment of young and/or fit patients.…”

Section: Introductionmentioning

confidence: 99%

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

Brown

Barrientos

Barr

et al. 2015

Blood

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103

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Section: Introductionmentioning

confidence: 99%

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

Brown

Barrientos

Barr

et al. 2015

Blood

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103

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“…37,38). There is a need of new treatment options that are effective on these patients and/or reduce or delay the development of refractoriness to these compounds.…”

Section: I3c Is An Orally Bioavailable Natural Small Chemical With Pomentioning

confidence: 99%

Indole-3-Carbinol Synergizes with and Restores Fludarabine Sensitivity in Chronic Lymphocytic Leukemia Cells Irrespective of p53 Activity and Treatment Resistances

Pérez-Chacón

Martínez‐Laperche

Rebolleda

et al. 2016

Clinical Cancer Research

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Purpose: Chronic lymphocytic leukemia (CLL) still is lacking a cure. Relapse and development of refractoriness to current treatments are common. New therapies are needed to improve patient prognosis and survival. Experimental design: Indole-3-carbinol (I3C) is a natural product with antitumor properties already clinically tested. The effect of I3C, F-ara-A, and combinations of both drugs on CLL cells from patients representing different Rai stages, IGHV mutation status, cytogenetic alterations, p53 functionality, and treatment resistances was tested, as well as the toxicity of these treatments in mice. Results: I3C induces cytotoxicity in CLL cells but not in normal lymphocytes. I3C strongly synergized with F-ara-A in all CLL cells tested, including those with p53 deficiency and/or F-ara-A resistance. The mechanism of cell death involved p53-dependent and -independent apoptosis. The combination of I3C + F-ara-A was equally effective in CLL cells irrespective of IGHV mutation stage and patient refractoriness. Moreover, CLL survival and treatment resistance induced by co-culturing CLL cells on stroma cells were overcome by the combinatory I3C + F-ara-A treatment. No toxicity was associated with the combined I3C + fludarabine treatment in mice. Conclusions: I3C in combination with F-ara-A is highly cytotoxic in CLL cells from refractory patients and those with p53 deficiency. The striking dose reduction index for F-ara-A in combination with I3C would reduce fludarabine toxicity while having a similar or better anti-CLL effectiveness. Moreover, the low toxicity of I3C, already clinically tested, supports its use as adjuvant and combinatory therapy in CLL, particularly for patients with relapsed or refractory disease. Clin Cancer Res; 22(1); 134–45. ©2015 AACR.

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“…при рецидивах, развившихся в течение 1 и 2 лет после достижения ремиссии соответственно. При поздних рецидивах медиана общей выживаемости не достигнута [10,11].…”

Section: Introductionunclassified

Ibrutinib in the Treatment of Relapsed Chronic Lymphocytic Leukemia

Stadnik¹,

Тимофеева²,

Strugov³

et al. 2018

Клиническая онкогематология

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РЕФЕРАТЦель. Оценить эффективность ибрутиниба при первых ранних рецидивах хронического лимфолейкоза (ХЛЛ) и у больных, получивших 2 линии и более предшествую-щей терапии. Анализ результатов лечения у пациентов с del(17p), мониторинг минимальной остаточной болезни (МОБ) и профиля безопасности ибрутиниба. Материалы и методы. Анализу подвергнуты результаты терапии ибрутинибом у 31 пациента c ХЛЛ. Бендамустин-и флударабин-содержащие режимы получили 28 чело-век. Медиана линий предшествующей терапии была 2 (диапазон 1-10). Показанием к началу лечения служил первый ранний рецидив (51 %, n = 16) и рецидив после 2 линий и более (49 %, n = 15). Ибрутиниб использовал-ся в монорежиме (n = 15), в комбинации с ритуксимабом (n = 14) и в сочетании с режимом R-BAC (n = 2). Методом FISH del(17p) выявлена у 9 (34 %) пациентов. Результаты. При медиане наблюдения 18 мес. (диапазон 7-42+ мес.) общая выживаемость (ОВ) составила 87 %, выживаемость без прогрессирования (ВБП) -77 %. Наи-более низкая МОБ через 1 год от начала терапии ибрути-нибом отмечалась при комбинированном использовании препарата с режимами иммунохимиотерапии (например, R-BAC). На срок 18 мес. ОВ в группе первых ранних реци-дивов составила 100 %, а в группе после 2 линий терапии и более -66 % (p = 0,02). ВБП на этот же срок наблюдения была значимо выше в группе первых ранних рецидивов (94 %) по сравнению с пациентами с предшествующим ле-чением (60 %) (p = 0,034). Наиболее частые нежелатель-ные явления: геморрагический диатез I-II степени (30 %), диарея I-II степени (10 %), пароксизмы фибрилляции пред-сердий (10 %) и артериальная гипертензия (10 %). У 3 (6 %) пациентов зарегистрированы тяжелые инфекционные ос-ложнения, успешно разрешившиеся на фоне комбиниро-ванной антибактериальной и антимикотической терапии. Заключение. Ибрутиниб эффективен при рецидивах ХЛЛ. Показатели ОВ и ВБП статистически значимо лучше у больных с первыми ранними рецидивами по сравнению с пациентами после 2 и более линий пред-шествующей ибрутинибу терапии. Наиболее глубокая элиминация опухолевого клона наблюдается при ис-пользовании комбинированных режимов иммунохи-миотерапии с ибрутинибом. Отмечалась удовлетвори-тельная переносимость препарата при приемлемом профиле токсичности. Летальных исходов от инфекци-онных осложнений не наблюдалось. ABSTRACTAim. To estimate ibrutinib effi cacy in the treatment of fi rst early CLL relapses and in patients with ≥ 2 lines of preceding therapy. Analysis of treatment results in patients with del(17p) and monitoring of minimal residual disease (MRD) and ibrutinib safety profi le. Materials & Methods. The analysis included the results of ibrutinib treatment in 31 patients with CLL. Twenty eight patients were treated by bendamustine and fl udarabine containing regimens. The median prior treatment lines were 2 (range 1-10). The indications for the treatment initiation were the fi rst early relapse in 51 % of cases (n = 16) and a relapse after 2 and more lines of therapy in 49 % of cases (n = 15). Ibrutinib was administered in mono-(n = 15) and combined therapy (n...

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The Treatment of Relapsed Refractory Chronic Lymphocytic Leukemia

Cited by 40 publications

References 67 publications

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

Indole-3-Carbinol Synergizes with and Restores Fludarabine Sensitivity in Chronic Lymphocytic Leukemia Cells Irrespective of p53 Activity and Treatment Resistances

Ibrutinib in the Treatment of Relapsed Chronic Lymphocytic Leukemia

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