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Therapeutic potential of new B cell-targeted agents in the treatment of elderly and unfit patients with chronic lymphocytic leukemia.

Rai KR - J Hematol Oncol (2015)

Bottom Line: Anti-CD20 monoclonal antibody therapy, which overall has improved response rates and survival in patients with CLL, has only recently been evaluated elderly and unfit patients.B cell-targeted agents such as the Bruton's tyrosine kinase inhibitor ibrutinib and the phosphatidylinositol 3-kinase inhibitor idelalisib are the first of a new generation of oral agents for CLL.Available clinical data suggest that these therapies have the potential to address the unmet need in elderly and unfit patients with CLL and result in clinical remission, and not merely symptom palliation and improved quality of life, which, by themselves, are also a reasonable goal.

View Article: PubMed Central - PubMed

Affiliation: Hofstra North Shore-LIJ School of Medicine and the North Shore-LIJ Cancer Institute, Lake Success, NY, USA. krai@nshs.edu.

ABSTRACT
Chronic lymphocytic leukemia (CLL), the most common adult leukemia in the Western world, is primarily a disease of the elderly, with most patients ≥65 years of age and having at least one major comorbidity. Aggressive chemoimmunotherapy regimens recommended to achieve remission and improve survival in young, fit patients are often poorly tolerated in elderly and/or less physiologically fit ("unfit") patients, necessitating alternative treatment options. Although patient age, fitness, and comorbidities are key considerations in the selection of a treatment regimen, historically, clinical trials have been limited to young, fit patients by virtue of the ethical concerns associated with potential end organ toxic effects that could worsen comorbidities. However, the availability of new therapies promises a shift to a research paradigm that encompasses the identification of optimal treatments for elderly and unfit patients. Anti-CD20 monoclonal antibody therapy, which overall has improved response rates and survival in patients with CLL, has only recently been evaluated elderly and unfit patients. B cell-targeted agents such as the Bruton's tyrosine kinase inhibitor ibrutinib and the phosphatidylinositol 3-kinase inhibitor idelalisib are the first of a new generation of oral agents for CLL. Available clinical data suggest that these therapies have the potential to address the unmet need in elderly and unfit patients with CLL and result in clinical remission, and not merely symptom palliation and improved quality of life, which, by themselves, are also a reasonable goal.

No MeSH data available.


Related in: MedlinePlus

Phase 1b/2 trial of ibrutinib monotherapy in elderly patients with CLL/SLL [61]. a Progression-free survival. b Overall survival. + = censored. CLL chronic lymphocytic leukemia, SLL small lymphocytic lymphoma. Reproduced with permission from [61]
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Fig4: Phase 1b/2 trial of ibrutinib monotherapy in elderly patients with CLL/SLL [61]. a Progression-free survival. b Overall survival. + = censored. CLL chronic lymphocytic leukemia, SLL small lymphocytic lymphoma. Reproduced with permission from [61]

Mentions: A total of 31 patients (CLL, n = 29) were enrolled, with a median age of 71 years; 74 % of patients were >70 years of age. Median time from initial diagnosis to study entry was 57.3 months; based on ECOG performance status (0, 74 %; 1, 26 %), patients were relatively fit, despite having several comorbidities. Median treatment duration was 21.0 months, during which relative dose intensity was 98.9 %. The most common overall AEs were diarrhea (68 %), nausea (48 %), and fatigue (32 %), and the most common grade 3 AEs were diarrhea (13 %) and hypertension (6 %). There was one grade 4 AE (thrombocytopenia) and no grade 5 AEs. Two patients discontinued because of AEs (grade 3 fatigue, grade 2 viral infection). The overall response rate was 71 %, with 13 % of patients achieving a CR. Exploratory subgroup analyses showed no differences in overall response, including in patients ≥70 and <70 years of age and in patients with and without high-risk cytogenetics. At 24 months, PFS and overall survival were 96.3 and 96.6 %, respectively. Median PFS was not reached, as only one patient progressed during the follow-up period (Fig. 4). Twenty-six patients (84 %) continued in the optional long-term extension study, the results of which have not yet been reported.Fig. 4


Therapeutic potential of new B cell-targeted agents in the treatment of elderly and unfit patients with chronic lymphocytic leukemia.

Rai KR - J Hematol Oncol (2015)

Phase 1b/2 trial of ibrutinib monotherapy in elderly patients with CLL/SLL [61]. a Progression-free survival. b Overall survival. + = censored. CLL chronic lymphocytic leukemia, SLL small lymphocytic lymphoma. Reproduced with permission from [61]
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522086&req=5

Fig4: Phase 1b/2 trial of ibrutinib monotherapy in elderly patients with CLL/SLL [61]. a Progression-free survival. b Overall survival. + = censored. CLL chronic lymphocytic leukemia, SLL small lymphocytic lymphoma. Reproduced with permission from [61]
Mentions: A total of 31 patients (CLL, n = 29) were enrolled, with a median age of 71 years; 74 % of patients were >70 years of age. Median time from initial diagnosis to study entry was 57.3 months; based on ECOG performance status (0, 74 %; 1, 26 %), patients were relatively fit, despite having several comorbidities. Median treatment duration was 21.0 months, during which relative dose intensity was 98.9 %. The most common overall AEs were diarrhea (68 %), nausea (48 %), and fatigue (32 %), and the most common grade 3 AEs were diarrhea (13 %) and hypertension (6 %). There was one grade 4 AE (thrombocytopenia) and no grade 5 AEs. Two patients discontinued because of AEs (grade 3 fatigue, grade 2 viral infection). The overall response rate was 71 %, with 13 % of patients achieving a CR. Exploratory subgroup analyses showed no differences in overall response, including in patients ≥70 and <70 years of age and in patients with and without high-risk cytogenetics. At 24 months, PFS and overall survival were 96.3 and 96.6 %, respectively. Median PFS was not reached, as only one patient progressed during the follow-up period (Fig. 4). Twenty-six patients (84 %) continued in the optional long-term extension study, the results of which have not yet been reported.Fig. 4

Bottom Line: Anti-CD20 monoclonal antibody therapy, which overall has improved response rates and survival in patients with CLL, has only recently been evaluated elderly and unfit patients.B cell-targeted agents such as the Bruton's tyrosine kinase inhibitor ibrutinib and the phosphatidylinositol 3-kinase inhibitor idelalisib are the first of a new generation of oral agents for CLL.Available clinical data suggest that these therapies have the potential to address the unmet need in elderly and unfit patients with CLL and result in clinical remission, and not merely symptom palliation and improved quality of life, which, by themselves, are also a reasonable goal.

View Article: PubMed Central - PubMed

Affiliation: Hofstra North Shore-LIJ School of Medicine and the North Shore-LIJ Cancer Institute, Lake Success, NY, USA. krai@nshs.edu.

ABSTRACT
Chronic lymphocytic leukemia (CLL), the most common adult leukemia in the Western world, is primarily a disease of the elderly, with most patients ≥65 years of age and having at least one major comorbidity. Aggressive chemoimmunotherapy regimens recommended to achieve remission and improve survival in young, fit patients are often poorly tolerated in elderly and/or less physiologically fit ("unfit") patients, necessitating alternative treatment options. Although patient age, fitness, and comorbidities are key considerations in the selection of a treatment regimen, historically, clinical trials have been limited to young, fit patients by virtue of the ethical concerns associated with potential end organ toxic effects that could worsen comorbidities. However, the availability of new therapies promises a shift to a research paradigm that encompasses the identification of optimal treatments for elderly and unfit patients. Anti-CD20 monoclonal antibody therapy, which overall has improved response rates and survival in patients with CLL, has only recently been evaluated elderly and unfit patients. B cell-targeted agents such as the Bruton's tyrosine kinase inhibitor ibrutinib and the phosphatidylinositol 3-kinase inhibitor idelalisib are the first of a new generation of oral agents for CLL. Available clinical data suggest that these therapies have the potential to address the unmet need in elderly and unfit patients with CLL and result in clinical remission, and not merely symptom palliation and improved quality of life, which, by themselves, are also a reasonable goal.

No MeSH data available.


Related in: MedlinePlus