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Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system that most often affects immunocompromised individuals. It is caused by the reactivation of the John Cunningham virus (JCV), which is found in latent form in the majority of adults. We describe a 59-year-old man with multiple myeloma who developed severe neurological deficits during treatment with ixazomib-based chemotherapy. A diagnosis of PML was established with gadolinium-enhanced magnetic resonance imaging (MRI) and by detection of JCV in the cerebrospinal fluid. Despite cessation of chemotherapy and treatment with mirtazapine, he had an inexorable neurological decline and died two months after presenting to hospital. Multiple myeloma and its treatments can predispose patients to opportunistic infections including PML. Although there have been case reports of PML in patients with multiple myeloma treated with bortezomib (a different proteosome inhibitor), this is, to our knowledge, the first documented case of PML in a patient treated with a regimen that includes ixazomib.

We used an interview-assisted survey of patients with chronic myeloid leukemia (cml) at a single tertiary care centre to explore patient reactions to and preferences for, and the risk-acceptability of, stopping tyrosine kinase inhibitor (tki) treatment. The study included patients with confirmed cml currently being treated with a tki. The survey was conducted by structured interview using a standard form. Patient preferences were explored in a case-based scenario using 0%&ndash, 100% visual analog scales and 5-point Likert scales. Data were analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables. Of 63 patients approached, 56 completed the survey. Participant responses suggest that the idea of stopping tki use is appealing to many patients if there is a chance of long-term stable disease and a high probability of response upon restarting a tki. Participants were more likely to stop their tki as the risk of relapse decreased. Participants reported loss of disease control and failure of disease to respond to treatment as important concerns if they chose to stop their tki. Given the current 60% estimated rate of relapse after discontinuation of tki therapy, most patients with cml chose to continue with tki. However, at the lower relapse rates reported with second-generation tkis, participants were more undecided, demonstrating a basic understanding of risk. Contrary to our hypothesis, neither compliance nor occurrence of side effects significantly affected patient willingness to stop their tki.

The Editor, Current Oncology June 23, 2014 We thank Villemagne et al. for their comments, and we will address some of the issues that they raised. It is important that clinicians understand patient concerns and values before key treatment decisions are made. Hypothetical scenarios such as “what if” or “when this occurs” are discussed routinely in close patient–physician relationships, and for that reason, we reject the assertion that our sample is not representative of patients with chronic myeloid leukemia (cml) who might be eligible for stopping tyrosine kinase inhibitors (tkis). We contend that it is not necessary for patients to have achieved a sustained deep molecular response (Bcr-Abl ≤ 0.0032%) to make informed responses to a hypothetical scenario. It is unknown whether a group of patients who have achieved a deep molecular response would respond differently than would patients whose molecular response might have not been optimal. For the second point, consecutive patients with cml being treated by the investigators were approached for participation in the study during the study period. We agree with the third comment that our single-centre study might have allowed for the opinion or influence of a small number of clinicians to have a significant impact on patient responses, which is explicitly stated in the Discussion section of the article. The reference cited by Villemagne et al. to support the statement that “studies of compliance in cml have shown a much more complex array of behaviours and choices” is also a single-centre study and subject to the same limitations1. In response to the measurement tool, Villemagne et al. suggest that the first two measures of patient preference for relapse rates are confounded with willingness to stop treatment. Again, it is important to understand that the patient scenario is laid out with the remarks that the questions are hypothetical, that the response will not affect current clinical care, and that the very first question is asking about willingness to stop. There is no assumption of willingness to stop in the first question. It was not our intention to use only patients who are in deep molecular response and who are willing to stop to assess risk acceptability. Rather, we wanted to gauge the response of the general cml population who might or might not be faced with that decision. The visual analog scales were not modified from their original formats (with a 0 labelled the worst imaginable health state and a “sad face”). That presentation did cause some difficulty in interpretation of the question by the patients, but it was clarified by the interviewer in a standardized fashion. We agree that patient compliance is complex, that our choices do not make a distinction between unintentional and deliberate noncompliance, and that self-reported measures of compliance are notoriously unreliable. The two references listed by Villemagne et al. as having validated measures for patient-reported outcomes of compliance and toxicity specific to cml have no documentation of the inclusion of cml patients in the studies2,3. The first study, by Morisky et al.2, dealt with adherence in hypertensive patients, and the second study, by Cleeland et al.3, categorized only 7 of 527 patients as having chronic leukemia in the outpatient setting, without clarifying the type of chronic leukemia. We agree that the evidence suggests that patients are more likely to misrepresent their treatment adherence in clinical settings; however, we conducted an interviewer-led study using an independent surveyor who had no involvement in patient care to minimize such bias. As discussed, conveying risk in treatment decisions is complex and is influenced by patient–physician communication and relationship4. Those interactions are also affected by physician beliefs about the quality of evidence, which influences how information about risk is conveyed to patients. Objective standardized patient education and decision tools can be useful adjuncts in such circumstances5. We have outlined the various limitations of our study, but it nevertheless represents real-life discussions that can arise with patients who are generally well informed and interested in taking greater ownership of their health. Larger studies of stopping tkis are being done, and we anticipate that the question of stopping will arise for some patients. Our study offers a glimpse of how patients might approach this issue. Thus, the average patient with cml on a tki approaching this hypothetical question based on a personal opinion of “compliance” and a personal view of side effects might or might not be willing to stop. Larger multicentre studies can be performed, but ultimately each patient makes a personal decision based on their own perceptions of level of “compliance,” severity of side effects, and risk acceptability. The main message of the paper is that patients are capable of balancing risk, and the choice to stop a tki should involve shared decision-making between the patient and the clinician, which has been reported to be the approach preferred by most patients with cancer6.