Bendamustine and its role in the treatment of unfit patients with chronic lymphocytic leukaemia: a perspective review

Al‐Sawaf, Othman; Cramer, Paula; Goede, Valentin; Hallek, Michael; Pflug, Natali

doi:10.1177/2040620717699365

Cited by 9 publications

(11 citation statements)

References 40 publications

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“…Despite advances in treatment for patients with CLL, there are currently no curative treatments; refractory disease (treatment failure/disease progression within 6 months of the last dose of therapy) and disease relapse (evidence of disease progression 6 months or more after achievement of complete response/partial response) after initial treatment is common [5] [6]. Patients with relapsed or refractory (R/R) disease generally have poor outcomes and their treatment remains highly challenging [7].…”

Section: Introductionmentioning

confidence: 99%

Overall Survival and Health Care Costs of Medicare Patients with Previously Treated Chronic Lymphocytic Leukemia

Reyes¹,

Gauthier²,

Shi³

et al. 2018

JCT

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Background: Bendamustine-based regimens are often used in the management of patients with chronic lymphocytic leukemia (CLL) but few studies have analyzed the comorbidity-and/or adverse event (CAE)-related healthcare costs in patients receiving these regimens in a real-world setting. Aims: To describe all-cause and CAE-related healthcare costs in relapse/refractory (R/R) elderly patients with CLL treated with bendamustine-based regimens in a real-world setting. Methods: Adult patients with R/R CLL who received bendamustine-based regimens on/after January 2010 were selected from the Medicare Limited Data Set (LDS) 5% Standard Analytic Files. Selected patients were classified into cohorts based on the two most prevalent bendamustine-based regimens observed (index treatment): 1) bendamustine + rituximab (BR cohort) and 2) bendamustine monotherapy (B-mono cohort). For each cohort, all-cause and CAE-related healthcare costs, while on treatment, were reported per-patient-per-month (PPPM). Overall survival (OS) rates following initiation of the index treatment were described using age-and gender-adjusted Kaplan-Meier curves. Results: A total of 275 patients were included in the BR cohort and 100 patients in the B-mono cohort. Most patients were male and the mean age was approximately 75 years old. During treatment, total all-cause healthcare costs were $14,520 PPPM for the BR cohort and $13,125 PPPM for the B-mono cohort-outpatient costs (mainly driven by CLL-drug costs) represented 86.1% of the total all-cause healthcare costs for the BR cohort and 69.8% for the B-mono cohort. CAE costs accounted for 58.3% of the total all-cause healthcare costs for the BR cohort and 66.9% for the B-mono cohort. Median OS was 35 months in the BR cohort and 21 months in the B-mono cohort. Conclusion: In this population of elderly patients with R/R CLL treated with bendamustine-based regimens,

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Section: Introductionmentioning

confidence: 99%

Overall Survival and Health Care Costs of Medicare Patients with Previously Treated Chronic Lymphocytic Leukemia

Reyes¹,

Gauthier²,

Shi³

et al. 2018

JCT

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“…Therefore, this strategy might be useful in patients with a higher tumor load and the necessity to achieve a quick response. 12 To confirm our in vitro results, we analyzed the efficacy of the combination in vivo, using the TCL1 AT mouse model of CLL that recapitulates tumor-microenvironment interactions. Mice treated with CC-292 experienced no detectable increase in lymphocytosis, similarly to the results observed in TCL-1 mice treated with the BTK inhibitor acalabrutinib.…”

Section: Discussionmentioning

confidence: 78%

“…In the blood stream, signals for cell activation are weaker and bendamustine might therefore exert higher cytotoxic activity. Therefore, this strategy might be useful in patients with a higher tumor load and the necessity to achieve a quick response …”

Section: Discussionmentioning

confidence: 99%

“…In addition, signals transmitted by the microenvironment play a key role in promoting cell survival and chemoresistance of CLL cells to bendamustine . Ongoing clinical trials explored the effects of bendamustine combinations with new generation monoclonal antibodies and novel targeted agents …”

Section: Introductionmentioning

confidence: 99%

“…11 Ongoing clinical trials explored the effects of bendamustine combinations with new generation monoclonal antibodies and novel targeted agents. 12 Ibrutinib, the first-in-class BTK inhibitor, is approved for the treatment of untreated CLL patients, 11,13 patients with relapsed or refractory disease, 14,15 and patients with 17p deletions. 16 However, most patients do not experience a complete response and a subset of patients develops resistance, mainly through mutations in BTK or PLCγ2.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Selective BTK inhibition improves bendamustine therapy response and normalizes immune effector functions in chronic lymphocytic leukemia

Lee-Vergés

Hanna

Yazdanparast

et al. 2019

Intl Journal of Cancer

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The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been shown to be highly effective in patients with chronic lymphocytic leukemia (CLL) and is approved for CLL treatment. Unfortunately, resistance and intolerance to ibrutinib has been observed in several studies, opening the door for more specific BTK inhibitors. CC‐292 (spebrutinib) is a BTK inhibitor with increased specificity for BTK and less inhibition of other kinases. Our in vitro studies showed that CC‐292 potently inhibited B‐cell receptor signaling, activation, proliferation and chemotaxis of CLL cells. In in vivo studies using the adoptive transfer TCL1 mouse model of CLL, CC‐292 reduced tumor load and normalized tumor‐associated expansion of T cells and monocytes, while not affecting T cell function. Importantly, the combination of CC‐292 and bendamustine impaired CLL cell proliferation in vivo and enhanced the control of CLL progression. Our results demonstrate that CC‐292 is a specific BTK inhibitor with promising performance in combination with bendamustine in CLL. Further clinical trials are warranted to investigate the therapeutic efficacy of this combination regimen.

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Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real‐world setting. A GIMEMA‐ERIC and US study

et al. 2020

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Bendamustine and its role in the treatment of unfit patients with chronic lymphocytic leukaemia: a perspective review

Cited by 9 publications

References 40 publications

Overall Survival and Health Care Costs of Medicare Patients with Previously Treated Chronic Lymphocytic Leukemia

Overall Survival and Health Care Costs of Medicare Patients with Previously Treated Chronic Lymphocytic Leukemia

Selective BTK inhibition improves bendamustine therapy response and normalizes immune effector functions in chronic lymphocytic leukemia

Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real‐world setting. A GIMEMA‐ERIC and US study

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