Moving towards patient-centered decision-making in chronic myeloid leukemia: assessment of quality of life and symptom burden

Abstract

F e r r a t a S t o r t i F o u n d a t i o n Editorials and Perspectives 206haematologica | 2014; 99 (2) response and on treatment recommendations. 7-9 While biochemical or laboratory abnormalities can be recorded objectively, clinical side-effects, for example, are typically recorded and collected by health care professionals (HCPs) who interpret and evaluate reports from the patients themselves. Probably only a few side-effects, like skin rash, alopecia, edema and fluid retention, can really be evaluated directly and, to a certain extent, objectively by the investigators. All available TKIs for first-line therapy, that is imatinib (i.e. 1st-generation TKIs) and dasatinib or nilotinib (i.e. 2nd-generation TKIs), have sideeffects that one should consider when deciding which therapy is best for the individual patient. However, some side-effects can be more frequent with a given TKI. As an example, while fatigue has been reported to be similar amongst the three TKIs, 10 others, such as rash, have been reported to be worse with both 2nd-generation TKIs. 11,12 In any case, in most studies, recording and assessing the type, the intensity and the duration of the side-effects are not planned, apart from formal reference to some internationally recognized scoring systems (e.g. NCI, SWOG). The data obtained with this methodology can be very different, even in company-sponsored, registrative studies.Just to illustrate how challenging it is to draw conclusions with regards to toxicity data, we report (for descriptive purposes only) five studies, [12][13][14][15][16] all in newly diagnosed, chronic phase, CML patients treated with imatinib 400 mg once daily (Table 1). Interestingly, the reported proportion of patients with any grade fatigue and muscle pain ranged from 8% and 34% (ENESTnd) 14 to 50% and 95% (IRIS), 13 respectively. Similarly, marked differences were also reported for all the other major groups of sideeffects (Table 1). The purpose of these studies, that tested imatinib versus other drugs, was to compare the type and Table 1. Percentage of newly diagnosed, chronic phase, CML patients who were reported to complain of the listed side-effects with imatinib. Side-effects (all grades)Pivotal trials comparing imatinib (400 mg once daily) © F e r r a t a S t o r t i F o u n d a t i o nseverity of the side-effects, but not the duration, between two different drugs. However, the reported data in the imatinib arm differed so greatly that it was difficult to assess the imatinib-related burden of symptoms, and can raise doubts as to the value of the comparison. Limitations of standard physician-reported toxicity with regards to the documentation of drug safety have been acknowledged 17 and have prompted the National Cancer Institute (NCI) to create a version of the NCI's Common Terminology Criteria for Adverse Events (PRO-CTCAE) that can be completed by patients themselves, providing direct patient feedback on their experience of their symptoms during treatment. 18In the context of CML treated with long-term TKI the...

Dasatinib in imatinib‐resistant or ‐intolerant chronic‐phase, chronic myeloid leukemia patients: 7‐year follow‐up of study CA180‐034

“…With the advent of BCR–ABL1 TKIs, CML is currently considered a chronic condition, in which most patients are able to achieve long‐term survival . Initial and continuing monitoring of responses is critical to ensure optimal management of CML, since early responses are predictive of long‐term outcomes .…”

“…The introduction of BCR–ABL1 tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML) resulted in improved patient prognosis, including greater survival rates, compared with the two previous standards of care . Survival in CML patients is now nearly identical to that of the general population .…”

The value of quality of life assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibitors

“…12 Specifically in CML research, we note that even in settings in which one would expect that side effects be collected in the most rigorous way (ie, registrative RCTs), extensive variation exists in their reporting, raising some concerns regarding the extent to which they reflect the actual patient burden. 13 For example, by comparing data from pivotal RCTs in newly diagnosed CP-CML patients treated with 400 mg/d imatinib, [14][15][16][17][18] we note that the reported proportion of patients with a given side effect (any grade) is not consistent across studies (Figure 1). …”

“…The difference is also impressive for grade 3/4 side effects: from a total of 18.1% in IRIS to a total of 3.6% in ENESTnd (data not shown). Adapted from Baccarani et al 13 Image and legend obtained from the Haematologica Journal website (www.haematologica.org) and reproduced with permission of the rights holder (Ferrata Storti Foundation, Pavia, Italy).…”

A Critical History of Chronic Myeloid Leukemia

“…But even TKIs are not completely specific, can cause important, and even life-threatening, clinical complications, as well as minor chronic side-effects that in the long term can become hard to tolerate 20–26. A careful monitoring of efficacy is necessary, based primarily on quantitative molecular testing and in case of failure also on mutational analysis, but also on cytogenetics, whenever molecular monitoring is not available or is not standardized according to the international scale 6,27,28. Monitoring is expensive, but the cost of careful monitoring is only a small fraction of the cost of treatment, and allows to make a proper use of any drug, from the clinical and also the financial point of view.…”