Limits...
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 3 trial of idelalisib + rituximab versus rituximab monotherapy in patients with relapsed CLL and clinically significant coexisting medical conditions [62]. a Progression-free survival. b Overall survival. CLL chronic lymphocytic leukemia. Reproduced with permission from [62]
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Phase 3 trial of idelalisib + rituximab versus rituximab monotherapy in patients with relapsed CLL and clinically significant coexisting medical conditions [62]. a Progression-free survival. b Overall survival. CLL chronic lymphocytic leukemia. Reproduced with permission from [62]

Mentions: Of the 220 patients enrolled, 78 % were ≥65 years of age, 85 % had a CIRS score >6 (median score, 8), and 40 % had at least moderate renal dysfunction; high-risk cytogenetics were common. Patients had received a median of three prior regimens. Median on-study treatment duration was 3.8 months for the idelalisib group and 2.9 months for placebo (not significant). At 24 weeks, PFS, the primary endpoint, was significantly higher in the idelalisib group compared with the placebo group (93 vs 46 %; hazard ratio (95 % CI), 0.15 (0.08–0.28); unadjusted P < 0.001). Median PFS was not reached in the idelalisib group, whereas it was 5.5 months in the placebo group (Fig. 5a). The treatment effect was similar in all prespecified subgroups, including patients <65 versus ≥65 years of age and those with high-risk cytogenetics and without high-risk cytogenetics. The idelalisib group also demonstrated significant improvement versus placebo in the overall response rate (81 13 %; P < 0.001; all responses were partial responses) and the lymph node response rate (93 versus 4 %; P < 0.001). The rate of 12-month overall survival was 92 % with idelalisib and 80 % with placebo (P = 0.02); median overall survival had not been reached at the time of the analysis (Fig. 5b).Fig. 5


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 3 trial of idelalisib + rituximab versus rituximab monotherapy in patients with relapsed CLL and clinically significant coexisting medical conditions [62]. a Progression-free survival. b Overall survival. CLL chronic lymphocytic leukemia. Reproduced with permission from [62]
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Phase 3 trial of idelalisib + rituximab versus rituximab monotherapy in patients with relapsed CLL and clinically significant coexisting medical conditions [62]. a Progression-free survival. b Overall survival. CLL chronic lymphocytic leukemia. Reproduced with permission from [62]
Mentions: Of the 220 patients enrolled, 78 % were ≥65 years of age, 85 % had a CIRS score >6 (median score, 8), and 40 % had at least moderate renal dysfunction; high-risk cytogenetics were common. Patients had received a median of three prior regimens. Median on-study treatment duration was 3.8 months for the idelalisib group and 2.9 months for placebo (not significant). At 24 weeks, PFS, the primary endpoint, was significantly higher in the idelalisib group compared with the placebo group (93 vs 46 %; hazard ratio (95 % CI), 0.15 (0.08–0.28); unadjusted P < 0.001). Median PFS was not reached in the idelalisib group, whereas it was 5.5 months in the placebo group (Fig. 5a). The treatment effect was similar in all prespecified subgroups, including patients <65 versus ≥65 years of age and those with high-risk cytogenetics and without high-risk cytogenetics. The idelalisib group also demonstrated significant improvement versus placebo in the overall response rate (81 13 %; P < 0.001; all responses were partial responses) and the lymph node response rate (93 versus 4 %; P < 0.001). The rate of 12-month overall survival was 92 % with idelalisib and 80 % with placebo (P = 0.02); median overall survival had not been reached at the time of the analysis (Fig. 5b).Fig. 5

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