Treatment of Elderly Patients With Chronic Lymphocytic Leukemia

An Unmet Clinical Need

Stefano Molica; Maura Brugiatelli; Fortunato Morabito; Felicetto Ferrara; Emilio Iannitto; Nicola Di Renzo; Silvana Capalbo; Pellegrino Musto; Francesco Di Raimondo

Disclosures

Expert Rev Hematol. 2013;6(4):441-449. 

In This Article

Age, Burden of Comorbidities & Fitness Criteria

Evidence for increased incidence of age-associated conditions in CLL patients, including coronary artery disease and cardiovascular risk factors, chronic pulmonary disease, low bone mineral density and frailty supports the concern that these patients may undergo an accelerated aging process.[18–19] Age has repeatedly shown to be an independent predictor of survival in CLL patients.[20–21] In a series accounting for 782 CLL patients observed over a 40-year period at a single institution, patients more than 75 years old had the worst clinical outcome in terms of overall survival (OS) when all causes of death (i.e., CLL- and no-CLL related) were consider (Figure 1). However, age by itself has the potential to alter the utility of prognostic testing given the higher mortality from competing health problems in older individuals.[22]

Figure 1.

Overall survival of chronic lymphocytic leukemia patients diagnosed over a 40-year period at a single institution (Catanzaro series). Patients are stratified according to age at the time of diagnosis.

Because of the availability of several newer therapies, an increasing interest toward a careful evaluation of the fitness status of CLL patients has been developed.[23] The different issues to be considered in addition to age are the burden of comorbidities and functional assessments.[24]

In search for reliable methods to assess fitness status, a multiparametric evaluation based on age, performance status, functional parameters such as activities of daily living (ADL), instrumental activity of daily living (iADL), number and severity of comorbidities, with the addition, if possible, of polypharmacy, mental status, nutritional status, geriatric syndromes and care-givers assessment should be considered. Interestingly, all these items are included in Comprehensive Geriatric Assessment.[25,26]

Performance status has represented for many years the only parameter utilized to define patient fitness and patient eligibility for relevant therapies. As far as CLL patient evaluation is concerned, ECOG score has been the most extensively utilized method for assessing performance status.[27] ADL and iADL,[28–30] which take into account the degree of self-sufficiency of patients in their daily life, have the advantage of accurately describing the patient's general condition and, in turn, the possible compliance to therapy. However, the assessment of ADL and iADL is time consuming and this prevents from an extensive use in daily practice.

In parallel with the assessment of functional status, the evaluation of comorbidities is crucial at the time of starting therapy in CLL.[31] In patients with solid tumours, two scales have been validated: the Charlson Comorbidity Index (CCI)[32] and the Cumulative Index Rating Scale (CIRS).[31] The CCI system takes into account both the number and severity of 19 pre-defined comorbid conditions.[32] The CIRS, more popular among haematologists, consists of 14 features of healthiness rated from 1 (no impairment to that organ/system) to 5 (impairment is life threatening).[33]

The German CLL Cooperative Group recently proposed a simplified classification of fitness status which defines patients as 'go-go' (i.e., fit), 'slow-go' (i.e., unfit) and 'no-go' (i.e., frail).[34] Accordingly, a CIRS value lower than 6 and creatinine clearance higher than 70 ml/min were the criteria utilized for considering patients eligible for inclusion into the CLL8 protocol.[35] In the authors' current practice, the eligibility for the fludarabine–cyclophosphamide–rituximab (FCR) regimen is also based on the patient's age and they recommend considering 70 years as a possible age threshold. This is in keeping with the recently updated CLL SIE-SIES-GITMO guidelines.[9]

In conclusion, although age should generally determine the goal of treatment in CLL, the patient's functional status rather than chronological age can be more informative. The applicability of the CIRS score in daily clinical practice needs validation in cohorts of unselected CLL patients representative of CLL real life. Furthermore, physicians should consider the improvement of quality of life the primary end point in the management of elderly CLL patients.

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