[Mark11]

Quality of life

by Mark11 on Thu Dec 03, 2015 5:45 pm

I realized there is no thread dedicated to the very important topic of quality of life. I was reading a study that I will post soon that commented that quality of life could be viewed as a primary endpoint in future studies. I think that would be great. Currently it seems to be a secondary endpoint or not discussed at all.

I have mentioned before that 3 studies were most influential in my choosing a therapy path. One of those was a quality of life study. I am starting this thread mostly for newly diagnosed patients. If anyone has any links to any studies that could be helpful to a newly diagnosed patient, please post them.

I figured I would start with the unfortunate reality that quality of life for older myeloma patients is poor when compared to other cancer patients. A newly diagnosed myeloma patient is in their late 60's.

Excerpt from Abstract:

Methods: HRQOL was examined with the 36-Item Short Form Health Survey, version 1, and the Veterans RAND 12-Item Health Survey in patients with selected cancers (kidney cancer, bladder cancer, pancreatic cancer, upper gastrointestinal cancer, cancer of the oral cavity and pharynx, uterine cancer, cervical cancer, thyroid cancer, melanoma, chronic leukemia, non-Hodgkin lymphoma, and multiple myeloma) and in individuals without cancer on the basis of data linked from the Surveillance, Epidemiology, and End Results cancer registry system and the Medicare Health Outcomes Survey. Scale scores, Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and a utility metric (Short Form 6D/Veterans RAND 6D), adjusted for sociodemographic characteristics and other chronic conditions, were calculated. A 3-point difference in the scale scores and a 2-point difference in the PCS and MCS scores were considered to be minimally important differences.

Results: Data from 16,095 cancer survivors and 1,224,549 individuals without a history of cancer were included. The results indicated noteworthy deficits in physical health status. Mental health was comparable, although scores for the Role-Emotional and Social Functioning scales were worse for patients with most types of cancer versus those without cancer. Survivors of multiple myeloma and pancreatic malignancies reported the lowest scores, with their PCS/MCS scores less than those of individuals without cancer by 3 or more points.

Conclusions: HRQOL surveillance efforts revealed poor health outcomes among many older adults and specifically among survivors of multiple myeloma and pancreatic cancer."

Source:

EE Kent et al, "Health-related quality of life in older adult survivors of selected cancers: data from the SEER-MHOS linkage," Cancer, Mar 2015 (abstract)

The second compares deterioration of quality of life when comparing patients older than 65 to those younger than those 65. It does not seem much better for the younger patients.

Abstract:

The objectives of this study were to compare health-related quality of life (HRQOL) between multiple myeloma (M​M) patients aged ≤65 and >65 years and to compare this with a normative population. Factors associated with HRQOL were identified. The population-based Eindhoven Cancer Registry was used to select M​M patients diagnosed from 1999 to 2010. Patients (n = 289) were invited to complete the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire Multiple Myeloma Module 20 (QLQ-MY20), and 212 patients responded (73 %). Data from the normative population (n = 568) were used for comparison. M​M patients >65 years scored better on emotional functioning (p < 0.05) and financial problems (p < 0.01) compared to patients ≤65 years. Patients ≤65 years reported better body image and future perspective (p < 0.01). Compared to the normative population, patients ≤65 years scored worse on all EORTC QLQ-C30 functioning scales and on global health/QOL, fatigue, pain, dyspnea, appetite loss, and financial problems (p < 0.01). Patients >65 years scored worse on social, physical, and role functioning and on global health/QOL, fatigue, pain, and dyspnea (p < 0.01). Younger patients had worse HRQOL compared to the normative population than elderly patients. Patients with comorbidities reported lower QOL. The longer the time since diagnosis, the better the physical functioning. No major differences in HRQOL were found between younger and older multiple myeloma patients. Compared to that of the normative population, HRQOL in younger patients was worse than that in older patients. The number of comorbidities and time since diagnosis were associated with HRQOL. M​M patients reported that a high symptom burden and therapy should, besides prolonging survival, be aimed at improving HRQOL.

Source:

MWM. van der Poel et al, "Elderly multiple myeloma patients experience less deterioration in health-related quality of life than younger patients compared to a normative population: a study from the population-based PROFILES registry," Annals of Hematology, April 2015 (abstract)

[Mark11]

Re: Quality of life

by Mark11 on Thu Dec 03, 2015 6:48 pm

As I mentioned above, here is a link to a good paper on quality of life with regard to myeloma patients.

Excerpts from the article:

"Survival of patients with multiple myeloma (multiple myeloma) has been extended markedly in the last 15 years and patients living with the disease for 10–15 years are no longer rare.1 However, in the absence of a curative treatment, the aim of therapy is to induce an objective response with the expectation that this leads to a prolongation of survival and, furthermore, to improve the patients’ quality of life.

Myeloma patients experience a variety of disease-related events and symptoms, such as bone destruction leading to pain, height reduction and body shape changes, and bone marrow failure, renal failure, immunodeficiency, as well as the psychosocial burden of a diagnosis of cancer. These aspects may have different importance for the patient in different periods of the disease. Furthermore, therapeutic interventions may produce troublesome side effects and functional impairments.2 Although prolongation of overall survival will always be a main goal of cancer treatment, health-related quality of life (HRQoL) is becoming increasingly important. To illustrate this, the US Food and Drug Administration (FDA) has emphasized HRQoL as an important end-point for approval of new anticancer drugs."

"Clinical trials in multiple myeloma patients should include HRQoL as a study endpoint making it possible to compare the study treatments taking into account the patients’ perspective. Because many of the new treatments in multiple myeloma may not give substantial prolongation of survival, HRQoL should be the primary endpoint in more studies. The bisphosphonate study by the Nordic group is a good example of altered decision-making based on HRQoL analyses.16 This randomized study compared the effect of 90 mg versus 30 mg of pamidronate on HRQoL and skeletal morbidity in patients with newly diagnosed multiple myeloma. In this trial, the primary endpoint was physical function estimated by the EORTC QLQ-C30 questionnaire 12 months after the start of treatment. The result was no difference in the primary endpoint and this was accompanied by no difference in skeletal-related events. Due to firm evidence based on HRQoL in a double-blind study, the recommendation for pamidronate treatment in multiple myeloma was changed from 90 mg to 30 mg monthly in Nordic countries. The patients were spared overtreatment and unnecessary side effects which are also risks for myeloma patients when so many treatment options are available.

Does it matter? To answer our initial question, there is no doubt that HRQoL adds an important dimension to the traditional endpoints in clinical trials and these measures should be combined in future studies. HRQoL could even serve as a primary endpoint in many trials."

Source:

AK Kvam, A Waage, "Health-related quality of life in patients with multiple myeloma - does it matter?", Haematologica, June 2015 (full text of article)

[Mark11]

Re: Quality of life

by Mark11 on Thu Dec 03, 2015 6:54 pm

One more for now. This a study from the UK. According to this study, the best quality of life a myeloma patient will experience is the first treatment-free interval. I can relate to this one, as I am now at 4.5 years of remission with no myeloma therapy.

Abstract:

Background: While the impact of various treatments on myeloma patients' health-related quality of life (HRQL) has been reported, the impact of a treatment-free interval (TFI) is currently unclear. The aims of this study were to assess if (1) a TFI is associated with a better HRQL vs. other treatment phases and (2) the length of the TFI influences HRQL.

Methods: A cross-sectional postal survey was conducted in the UK. The survey was sent to 605 multiple myeloma patients via the charity Myeloma UK and asked patients to rate their HRQL using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ-MY20 and the EQ-5D. The results were analysed using ordinary least squares regression.

Results: Surveys of 402 (67 %) were returned; 370 (61 %) were considered eligible for analysis. Results demonstrated that being in a first TFI relative to other treatment phases and experiencing a longer TFI were significantly associated with better HRQL as assessed by various domains of the QLQ-C30, MY20 and EQ-5D.

Conclusion: Patients enjoy better HRQL when in their first TFI, and the length of the TFI also positively impacts on HRQL This information may be important for patients and their physicians making treatment decisions and has implications for treatment protocols incorporating extended therapy.

Article:

S Acaster et al, "Impact of the treatment-free interval on health-related quality of life in patients with multiple myeloma: a UK cross-sectional survey," Supportive Care in Cancer, August 2012 (abstract)

[Mark11]

Re: Quality of life

by Mark11 on Mon Dec 07, 2015 7:44 pm

I wanted to add a couple of more studies to the list. The first certainly does not seem to show anything that is not to be expected, but I wanted to post it as it appears to have been put together by doctors at Dana Farber and Moffitt and was published in 2015. I think it is great that they looked at the quality of life for their patients and were looking for a way to measure it. What is published does not mention any therapies but the small group of patients likely are being treated with novel agents.

"PURPOSE:

Little qualitative research exploring the impact of multiple myeloma (multiple myeloma) and its treatment on the health-related quality of life (HRQL) of patients has been published. This study aimed to explore the burden of multiple myeloma symptoms and treatment and the impact of these on HRQL. A model was developed to illustrate key concepts and their interrelationships.

METHODS:

Patients with multiple myeloma were recruited to this cross-sectional, qualitative study through a patient panel and at two clinical sites in the USA. An interview discussion guide was developed using a review of published literature and interviews with experienced multiple myeloma clinicians. In-depth, semistructured telephone interviews with multiple myeloma patients were conducted to explore their experiences of the disease and its treatment. Data were analyzed using a thematic analysis approach.

RESULTS:

Twenty multiple myeloma patients at various stages of treatment participated in open-ended, semistructured interviews. Patients reported both current and previous multiple myeloma symptoms; most had experienced fatigue and pain. Other commonly reported symptoms were fractures, anemia, neuropathy, aches, and infections. multiple myeloma treatment was found to have a negative impact on patients' HRQL; treatment-related adverse events included fatigue, neuropathy, insomnia, and gastrointestinal symptoms. multiple myeloma treatment placed a substantial psychological and physical burden on patients, disrupting social activities, decreasing independence, and impacting on relationships. A model was developed to illustrate the relationship between these concepts.

CONCLUSION:

The conceptual model developed in this study illustrates the many aspects of multiple myeloma and its treatment and how they can have a negative impact on patients' HRQL."

http://www.ncbi.nlm.nih.gov/pubmed/25708126

[Mark11]

Re: Quality of life

by Mark11 on Mon Dec 07, 2015 8:00 pm

I thought this was an interesting study that comes from Mayo that I wanted to get into this thread. I will post the abstract and some of the interesting discussion at the end. I probably should have posted it right after the previous study, as patients considering maintenance until progression will not get to enjoy the treatment free interval discussed in that study. I like it when studies show what patients find important as opposed to just treatment stats with no discussion of quality of life issues with respect to the potential benefit of the therapy. This was published in 2013.

"BACKGROUND:

Two randomized trials have demonstrated improved progression-free survival (PFS) with lenalidomide maintenance after autologous transplantation for multiple myeloma (multiple myeloma). Overall survival (OS) results are conflicting, and quality-of-life (QOL) data are lacking. The authors conducted a systematic survey of patients with multiple myeloma regarding what constitutes a meaningful benefit that would make burdens of maintenance treatments (toxicity and cost) acceptable.

METHODS:

A self-administered survey was mailed to 1159 consecutive, living patients who were evaluated at Mayo Clinic. The survey provided background information on the standard of care for multiple myeloma and data on maintenance. Patients were asked to estimate the magnitude of OS benefit that would be acceptable for various degrees of toxicity and cost.

RESULTS:

Of 1159 surveys sent, 886 patients (83.2%) responded, and 736 patients returned a completed survey (66% raw response rate). The most worrisome potential toxicity was identified as peripheral neuropathy by 27% of patients, cytopenias by 24%, deep vein thrombosis by 20%, fatigue by 15%, nausea by 8%, and diarrhea/constipation by 7%. If treatment was free, had no toxicity, and the OS benefit was ≤1 year, then 49% of patients indicated that they would choose maintenance; with moderate toxicity, this proportion decreased to 42%. Adding a treatment cost of $25 per month decreased the proportion that would choose maintenance to 39% of patients.

CONCLUSIONS:

The current results indicated that willingness to receive maintenance treatment declined when actual benefits were provided in concrete numeric terms compared with a general statement of PFS benefit. The authors also observed that the magnitude of benefit required to consider maintenance was affected by cost and toxicity."


"In personal communication with patients who contacted us with regards to the survey, patients had a wide range of perspectives and preferences. On one end of the spectrum was a patient of the principal investigator’s, who stated that without maintenance she is currently able to “think about” her multiple myeloma once every three months and that maintenance would cause her to “think about” her myeloma daily. Consistent with this perspective, she chose not to fill out the survey as it would have required her to “think about” her myeloma. On the other end of the spectrum, a gentleman whom had had myeloma for over 3 years stated that he would tolerate “ANY” toxicity and “ANY” expense to gain a “single day” of life. Such a dramatic difference in perspectives of the two patients has obvious implications for providing personalized recommendations."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855162/

[Nancy Shamanna]

Re: Quality of life

by Nancy Shamanna on Mon Dec 07, 2015 10:20 pm

Thanks for posting this study, Mark. It was very informative regarding maintenance chemo, HRQOL, and how patients reacted to their situations. Thankfully in Canada Revlimid is now approved for maintenance treatments, whereas previously thalomid may have been used for that.

[Mark11]

Re: Quality of life

by Mark11 on Wed Dec 09, 2015 4:19 pm

Thanks, NancyS. That is great that Revlimid is now approved for maintenance in Canada. Definitely better than thalidomide with regard to quality of life for the patients!

[Mark11]

Re: Quality of life

by Mark11 on Wed Dec 09, 2015 4:28 pm

Here is a study from ASH 2015. I was especially interested in this study because they surveyed younger myeloma patients that are still working. They gave patients a list of the main toxicities from trials using novel agents and than asked them for their preferences with regard to the therapies. You pick up things like patients would be willing to give up on average of 4 months of progression free survival if they could take an oral therapy as opposed to an IV therapy.

Abstract:

Introduction: Patients' individual preferences for specific treatment attributes are an important factor to consider in treatment decisions. This area of research is relatively underexplored for patients with multiple myeloma (multiple myeloma).

Aims: To understand multiple myeloma patients' strength of preference for method of administration and for avoiding specific adverse events (AEs).

Methods: AEs were selected from trials of multiple myeloma treatments used globally across the disease course: lenalidomide (FIRST, MM-009/010), bortezomib (VISTA, APEX, MMY-3021), thalidomide (IFM 99-06), pomalidomide (MM-003), and carfilzomib (PX-171-003, -004, -005). AEs selected for evaluation were narrowed down to 12, based on discussions with multiple myeloma patients, from a list of hematologic and non-hematologic AEs with a grade 3/4 incidence > 5% and the greatest difference in rate of occurrence across trials: bone pain, febrile neutropenia, hypokalemia, hyponatremia, infection, lymphopenia, neuralgia, neutropenia, peripheral neuropathy, renal adverse reaction, and thrombocytopenia and thromboembolic events. multiple myeloma patients were recruited to complete an online survey. Following an introductory tutorial, patients completed 14 discrete choice cards on which they selected their preferred option between 2 hypothetical treatments with varying combinations of AEs (absent/present), route of administration (oral, subcutaneous [SC], intravenous [IV]), and progression-free survival (PFS; 22, 24, or 26 months, based on evidence of first-line multiple myeloma treatment). Results were expressed as odds ratios (ORs) and coefficients. Strength of preference was converted into a willingness to trade (WTT) PFS months to receive preferred choice of treatment.

Results: Four hundred patients from 8 countries participated in the survey: Canada (13; 3.3%), Denmark (9; 2.3%), France (68; 17.0%), Germany (65; 16.3%), Italy (89; 22.3%), Spain (81; 20.3%), Sweden (11; 2.8%), and the United Kingdom (64; 16.0%). Of the respondents, 28.8% were on their first treatment, 70.0% of patients reported having switched treatment. The majority (58.7%) were male, with a mean age of 40 years. Patients showed a preference for oral vs IV administration (OR, 0.875 [95% CI, 0.78-0.98]; P = .020), and there was a trend toward preferring oral over SC administration (OR, 0.897 [95% CI, 0.80-1.01]; P = .067). Strength of preference declined in patients with prior treatments. Patients expressed a statistically significant preference (P < .01) to avoid (OR < 1) all presented grade 3/4 AEs, except for hematologic AEs: thrombocytopenia (OR [P value]: 0.904 [.23]), neutropenia (0.911 [.30]), and lymphopenia (0.916 [.39]) for first treatment patients, and neutropenia (0.XXXX [.08]) for patients with prior therapy. The relative importance of bone pain, infection, and thromboembolic events was lower in patients with prior therapies, while the relative importance of grade 3/4 neuralgia, febrile neutropenia, and renal adverse reaction increased. The table shows patient preferences as coefficients, and by months of PFS WTT. Example: Patients on their first treatment would be WTT 4.33 mos of PFS to receive oral vs IV administration.

Conclusions: Study results display important findings concerning preferences of younger, working-age multiple myeloma patients on individual AEs and methods of administration. Patients expressed smaller preference for avoiding hematologic AEs, such as neutropenia, lymphopenia, and thrombocytopenia, and an increasing relative importance to avoiding some symptomatic AEs (eg, neuropathy, neuralgia, renal adverse reaction, and febrile neutropenia) over the course of their disease. Patient preference should be considered when making treatment decisions. Future analyses could explore subgroups based on demographics and disease history, including prior AEs.

Reference:

X Leleu et al, "Assessment of Multiple Myeloma Patient Preferences on Treatment Choices: An International Discrete Choice Study," ASH 2015 annual meeting abstract #2086 (Dec 2015)

[wvmedic]

Re: Quality of life

by wvmedic on Wed Dec 09, 2015 10:30 pm

Thank you very much for posting these studies.

This is the bottom line for myself and I want and need to be able to convey this information to my 48 year old Wife. I hope very much that her Doctor will be able to provide us with the information to make an informed decision.

I have been in the medical field for 23 years and I understand quality of life. I am a realistic person, the reality of what I see on a daily basis. With the Patients I come in contact with is they have a poor quality of life. Hemodialysis Patients for example, I don't know the statistical data. I'm not a mathematician, just what I have seen with my own eyes over the past 23 years. If you walk into a dylisas center and look around, of about 50 Patients. Likely 2 walk, drive, work and live a normal day to day life. 10 of the Patients will be transported by ambulance to and from there treatment, the remaining Patients appear to be worn down, general over all poor health with no apparent quality of life.

I would want to live the best quality of life I could for the remainder of my life. Even if that ment it would significantly be cut short.

My opinion of quality of life is much different than what I see as acceptable to other health care providers. I'm not sure if it is that they themselves live on hopes and transfer that to hope for their Patients. Even when it is obvious the is no improvement in their condition or quality of life with treatment.

Jeff

[Nancy Shamanna]

Re: Quality of life

by Nancy Shamanna on Thu Dec 10, 2015 9:33 am

Mark, I also read the abstract of the poster presentation you posted concerning the preferences of younger, working age patients, average age 40. I think that this is the sort of study used to determine how to advocate for certain drugs too. Also, any of us in the older contingent do not wish to have non-hematologic adverse events (AEs) such as blood clots, renal issues, bone pain or other serious health issues, either. it seems that hematologic AE's such as neutropenia and other aspects of low blood counts would be preferable in choosing a treatment. For patients not newly diagnosed , but further along their myeloma cancer journey, there was more of a acceptance of trying treatment regimens that would include taking more risks of non-hematologic AE's.

I heard Dr. Leuleu speak at two patient education events two years ago and was really impressed at his scientific brilliance. He is from Lyons France I think.

Thanks for posting this abstract.