Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome

Iurlo, Alessandra; Nobili, Alessandro; Latagliata, Roberto; Bucelli, Cristina; Castagnetti, Fausto; Breccia, Massimo; Abruzzese, Elisabetta; Cattaneo, Daniele; Fava, Carmen; Ferrero, Dario; Gozzini, Antonella; Bonifacio, Massimiliano; Tiribelli, Mario; Pregno, Patrizia; Stagno, Fabio; Vigneri, Paolo; Annunziata, Mario; Cavazzini, Francesco; Binotto, Gianni; Mansueto, Giovanna; Russo, Salvatore; Falzetti, Franca; Madon, E; Gugliotta, Gabriele; Storti, Sergio; D'Addosio, Ada; Scaffidi, Luigi; Cortesi, Laura; Cedrone, Michele; Rossi, Antonella Russo; Avanzini, Paolo; Echavarría‐Pinto, Mauro; Spadea, Antonio; Celesti, Francesca; Giglio, Gianfranco; Isidori, Alessandro; Crugnola, Monica; Calistri, Elisabetta; Sorà, Federica; Rege‐Cambrin, Giovanna; Sica, Simona; Luciano, Luigiana; Galimberti, Sara; Orlandi, Ester; Bocchia, Monica; Tettamanti, Mauro; Saglio, Giuseppe; Rosti, Gianantonio; Mannucci, Pier Mannuccio; Cortelezzi, Agostino

doi:10.18632/oncotarget.11657

Cited by 33 publications

(15 citation statements)

References 24 publications

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“…Postoperative outcomes (e.g., postoperative complications, delirium, extended hospital stay, and emergency department visit after cancer surgery) were evaluated in 11/47 studies (23%; Table ) . Chemotherapy‐related outcomes, such as chemotherapy‐related toxicities, chemotherapy completion, hospitalization after chemotherapy, complete remission (CR), chemotherapy dose reductions or delay, and blood transfusion, were evaluated in 12/47 studies (26%; Table ) . Frailty, falls, and physical and functional outcomes were evaluated in 7/47 studies (15%; Table ) .…”

Section: Discussionmentioning

confidence: 99%

“…Frailty, falls, and physical and functional outcomes were evaluated in 7/47 studies (15%; Table ) . Survival outcomes were assessed in 12/47 studies (26%; Table ) . Other outcomes (e.g., medication adherence, caregiver burden and alternative medications use; supplemental online Table 3) .…”

Section: Discussionmentioning

confidence: 99%

“…See Table . Of the 12 studies that examined the association between PP and chemotherapy‐related outcomes, 9 evaluated chemotherapy toxicity . The cancer types and treatments in these studies were heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

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Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis

et al. 2019

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Background Polypharmacy (PP) and potentially inappropriate medications (PIM) are highly prevalent in older adults with cancer. This study systematically reviews the associations of PP and/or PIM with outcomes and, through a meta‐analysis, obtains estimates of postoperative outcomes associated with PP in this population. Materials and Methods We searched PubMed, Embase, Web of Science, and Cochrane Register of Clinical Trials using standardized terms for concepts of PP, PIM, and cancer. Eligible studies included cohort studies, cross‐sectional studies, meta‐analyses, and clinical trials which examined outcomes associated with PP and/or PIM and included older adults with cancer. A random effects model included studies in which definitions of PP were consistent to examine the association of PP with postoperative complications. Results Forty‐seven articles met the inclusion criteria. PP was defined as five or more medications in 57% of the studies. Commonly examined outcomes included chemotherapy toxicities, postoperative complications, functional decline, hospitalization, and overall survival. PP was associated with chemotherapy toxicities (4/9 studies), falls (3/3 studies), functional decline (3/3 studies), and overall survival (2/11 studies). A meta‐analysis of four studies indicated an association between PP (≥5 medications) and postoperative complications (overall odds ratio, 1.3; 95% confidence interval [1.3–2.8]). PIM was associated with adverse outcomes in 3 of 11 studies. Conclusion PP is associated with postoperative complications, chemotherapy toxicities, and physical and functional decline. Only three studies showed an association between PIM and outcomes. However, because of inconsistent definitions, heterogeneous populations, and variable study designs, these associations should be further investigated in prospective studies. Implications for Practice Polypharmacy and potentially inappropriate medications (PIM) are prevalent in older adults with cancer. This systematic review summarizes the associations of polypharmacy and PIM with health outcomes in older patients with cancer. Polypharmacy and PIM have been associated with postoperative complications, frailty, falls, medication nonadherence, chemotherapy toxicity, and mortality. These findings emphasize the prognostic importance of careful medication review and identification of PIM by oncology teams. They also underscore the need to develop and test interventions to address polypharmacy and PIM in older patients with cancer, with the goal of improving outcomes in these patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis

et al. 2019

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“…Drug‐drug interactions are a challenge to administering TKI therapy in older CML patients . A study conducted on 296 patients from 35 Italian Institutions showed that polypharmacy (≥5 drugs) in very old CML patients (aged ≥75 years) treated with imatinib did not alter the dosage, cytogenetic and molecular responses, or hematologic and extra‐hematologic toxicity compared with patients without polypharmacy …”

Section: Ponatinib In Chronic Myeloid Leukemiamentioning

confidence: 99%

The multi‐tyrosine kinase inhibitor ponatinib for chronic myeloid leukemia: Real‐world data

Luciano

Annunziata

Attolico³

et al. 2020

European J of Haematology

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Development of the highly selective targeted tyrosine kinase inhibitors (TKIs) has expanded the therapeutic options for chronic myeloid leukemia (CML). Patients undergoing TKI therapy should be closely monitored to ensure that the best therapeutic response and quality of life are achieved, and to control suboptimal responses and adverse events. Despite the high rate of response using current first‐line TKIs, treatment failure may still occur, and resistance is considered a challenge in the treatment of patients with CML. The third‐generation TKI, ponatinib, is a potent orally bioavailable pan BCR‐ABL inhibitor that inhibits both wild‐type and mutant BCR‐ABL1 kinase, including the “gatekeeper” T315I mutation, which is resistant to all other currently available TKIs. This paper reviews the effectiveness, feasibility, and safety of ponatinib in the real‐life clinical management of CML. Potential prognostic factors in identifying patients most likely to benefit from ponatinib treatment will be discussed, and case presentations illustrating situations encountered in real‐life clinical practice are described. Ponatinib is effective in patients who have received prior TKIs in clinical studies as well as under real‐life conditions. Nevertheless, the risk/benefit balance must be evaluated for each patient, particularly considering disease state, mutational status, treatment line, intolerance/resistance to prior TKIs, age, frailty, and specific comorbidities.

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“…Notably, to this point, such studies have not shown polypharmacy to be a risk factor for poorer CML-related outcomes among elderly patients. 63 Factors associated with the long-term burden of CML, including treatment satisfaction and adherence, and the impact of chronic AEs on quality of life can be informed by RWE studies. 2,38 The potential utility of RWE studies in this regard is highlighted by the development of the MD Anderson Symptom Inventory for CML, a questionnaire used for evaluating a patient's quality of life.…”

Section: Weaknesses and Challenges Associated With Rwementioning

confidence: 99%

The Case for Real-world Evidence in the Future of Clinical Research on Chronic Myeloid Leukemia

Webster

Smith

2019

Clinical Therapeutics

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Purpose: In light of recently published guidelines from the US Food and Drug Administration (FDA) on the communication of real-world data (RWD) and real-world evidence (RWE) to support regulatory decision making, it is important to understand how such data are developed, the limitations of these data, and how to best use RWD to improve patient care. Historically, the use of RWE has been approached with skepticism because of its often-retrospective nature compared with data from conventional randomized controlled trials (RCTs). This review discusses the role and function of RWE and RWD in clinical research. We summarize the types of RWE used in clinical research, outline the challenges and limitations involved with these data, and suggest how these types of analyses can supplement results from clinical trials to foster a more complete understanding of a drug or disease area of interest. In particular, we focus on the role of RWE in investigating chronic myeloid leukemia (CML) and tyrosine kinase inhibitor therapy for CML. Methods: We reviewed FDA guidance on the use of RWE and conducted a PubMed literature search to evaluate published data from real-world studies in CML. Findings: RWE includes analysis of RWD gathered from nonconventional sources, including patient registries, observational studies, and social media, among others. Importantly, although real-world studies do not adhere to the same degree of controlled conditions and predefined patientmanagement strategies as do conventional clinical trials, analyses resulting from these studies can be held to a high degree of validation and standardization, making them as meaningful as those from RCTs. In CML, RWE has informed early treatment milestones and has provided a window into patient perspectives regarding treatment. These types of analyses have already informed and can continue to inform disease management. These improvements in disease management, in turn, will help clinicians to better forecast treatment challenges and allow for the optimization of future treatment paradigms. Implications: Real-world studies are different from conventional RCTs and therefore provide insight into distinct aspects of treatment and patient outcomes. Together with results from clinical trials, RWE can help to illustrate a more complete picture of the tolerability, effectiveness, and impact of a drug. The recently published guidelines indicate that the FDA expects a growing role for RWE. (Clin Ther.

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Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome

Cited by 33 publications

References 24 publications

Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis

Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis

The multi‐tyrosine kinase inhibitor ponatinib for chronic myeloid leukemia: Real‐world data

The Case for Real-world Evidence in the Future of Clinical Research on Chronic Myeloid Leukemia

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