The importance of frailty assessment in multiple myeloma: a position statement from the Myeloma Scientific Advisory Group to Myeloma Australia.

Multiple myeloma (MM) is a disease of older people, yet factors relating to comorbidity and frailty may threaten treatment tolerability for many of this heterogenous group. There has been increasing interest in defining specific and clinically relevant frailty assessment tools within the MM population, with the goal of using these frailty scores, not just as a prognostic instrument, but also as a predictive tool to allow for a frailty-adapted treatment approach. This paper reviews the various frailty assessment frameworks used in the evaluation of patients with MM, including the International Myeloma Working Group Frailty Index (IMWG-FI), the Mayo Frailty Index and the simplified frailty scale. While the IMWG-FI remains the most widely accepted tool, the simplified frailty scale is the most user-friendly in busy day-to-day clinics based on its ease of use. This paper summarises the recommendations from the Myeloma Scientific Advisory Group (MSAG) of Myeloma Australia, on the use of frailty assessment tools in clinical practice and proposes a frailty-stratified treatment algorithm to aid clinicians in tailoring therapy for this highly heterogeneous patient population.

Cost-Effectiveness of Extracorporeal Photopheresis for the Treatment of Patients With Erythrodermic (Stage T4, M0) Cutaneous T-Cell Lymphoma in the Australian Setting.

OBJECTIVES: Cutaneous T-cell lymphoma (CTCL) is a rare and incurable disease, and patients currently experience a lack of treatment options in Australia. This analysis evaluated the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard of care therapy for the treatment of patients with erythrodermic (stage T4, M0) CTCL, who are refractory to previous systemic treatment. METHODS: A Markov model was developed from the perspective of the Australian government. Health states were treatment specific and transition probabilities were modeled from time-to-next-treatment data from a published Australian observational study of ECP and comparator treatments. Quality of life utility values were based on psoriasis as a proxy for CTCL, which was validated by consultation with local clinicians. The time horizon for the model was 5 years. The ECP treatment regimen was compared with a weighted treatment comparator based on results of a treatment survey and Australian prescribing data. RESULTS: ECP as a second-line treatment option for CTCL was less costly and more effective than other treatment strategies. ECP had an average cost saving of $37 592 and incremental quality-adjusted life-year gained of 0.20 to 0.21, attributed to patients being able to better tolerate ECP thus avoiding subsequent treatment with high-cost alternatives. CONCLUSIONS: This is the first published cost-utility analysis of ECP for CTCL. This analysis demonstrates that ECP is a cost-effective option for the treatment of patients with erythrodermic CTCL in Australia.

The course of anxiety, depression and unmet needs in survivors of diffuse large B cell lymphoma and multiple myeloma in the early survivorship period.

PURPOSE: The purpose of the study is to examine the course of anxiety, depression and unmet needs in diffuse large B cell lymphoma (DLBCL) and multiple myeloma (MM) survivors in the first 2 years post diagnosis. METHODS: DLBCL and MM survivors, recruited through the Victorian Cancer Registry, completed two interviews approximately 7 and 15 months post diagnosis. Hospital Anxiety and Depression Scale (HADS) and Supportive Care Needs Survey (SCNS-SF34) were completed at both interviews. Primary outcomes were prevalence of anxiety, depression and unmet needs (any or moderate-high). Generalized estimating equation examined whether course of anxiety, depression and unmet needs differed between the two cancers. RESULTS: Overall, 236 DLBCL and 178 MM survivors completed both telephone interviews. Course of anxiety differed (p < 0.01) with rate increasing in DLBCL (14 to 22%) while remaining stable for MM (15 to 12%). Course of depression also differed (p < 0.01), decreasing for MM (22 to 12%) and remaining stable for DLBCL (15 to 16%) survivors. Change in unmet needs was generally similar for the two cancer groups, except for moderate to high psychological needs (p < 0.05). CONCLUSIONS: Patterns of change in anxiety and depression in first 2 years post diagnosis differ for DLBCL and MM survivors. IMPLICATIONS FOR CANCER SURVIVORS: Studying psychological outcomes in mixed haematological cancer samples may be inappropriate, at least in the early survivorship phase. Separate studies of the experiences of people with the different haematological cancer subtypes are needed to ensure psychosocial and supportive care interventions are appropriate to the needs of individuals with different haematological cancers.

Mycosis fungoides and Sézary syndrome: Current challenges in assessment, management and prognostic markers.

Mycosis fungoides and Sézary syndrome are the most common variants of the cutaneous T-cell lymphomas. Assessment of a patient with a suspected diagnosis requires thorough history taking and physical examination, in combination with skin biopsy. In some cases flow cytometry, molecular studies and imaging are also required in order to diagnose and stage the disease. Staging is derived from the tumour-node-metastasis-blood classification and is currently our best attempt to stratify prognosis and hence guide management in this complex disease. Many other clinical, biological and pathological factors may help to distinguish groups at risk and predict prognosis more accurately. Management remains heavily guided by staging, such that patients with early-stage disease generally begin treatment with skin-directed or local therapies and those with advanced-stage disease have many treatment options, including chemotherapy, the use of biological agents, local and total body radiotherapy, as well as haematopoietic stem cell transplantation. Besides staging, many other patient-related factors influence the treatment strategy, particularly where symptom relief is paramount. There are many challenges remaining in the study of Mycosis fungoides and Sézary syndrome and, given the rarity of the disease, concerted worldwide efforts are required to conduct efficient and effective research.

Low uptake of upfront autologous transplantation for myeloma in a jurisdiction with universal health care coverage: a population-based patterns of care study in Australia.

BACKGROUND: Guidelines for the management of symptomatic multiple myeloma (MM) recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible patients. PATIENTS AND METHODS: Using population-based data, we examined the characteristics of transplant-eligible patients who do not undergo upfront ASCT. Altogether, 686 newly diagnosed MM cases were identified through the population-based central cancer registry in Victoria, Australia from 2008 to 2009. We performed a detailed review of clinical notes and follow-up for at least 12 months after diagnosis for a subset of 225 patients who were aged < 70 years at diagnosis and had symptomatic MM. RESULTS: Of these 225 patients, 123 (55%) proceeded to receive upfront ASCT. Patient and disease factors associated with not receiving upfront ASCT were the presence of severe medical comorbidities, MM-associated renal impairment, and initial referral to a medical oncologist rather than a hematologist. Place of residence (rural vs. metropolitan) was not significant. Of 121 patients aged < 65 years at diagnosis who had minor or no comorbidities, only 75 (62%) proceeded to upfront ASCT. CONCLUSION: A substantial percentage of apparently transplant-eligible patients with newly diagnosed MM do not proceed to upfront ASCT. Community practice appears to diverge from clinical guidelines. The reasons for this divergence require further study but reasons may include perceptions of toxicity vs. benefits of upfront ASCT.

A cost analysis of febrile neutropenia management in Australia: ambulatory v. in-hospital treatment.

BACKGROUND: Adult febrile neutropenic oncology patients, at low risk of developing medical complications, may be effectively and safely managed in an ambulatory setting, provided they are appropriately selected and adequate supportive facilities and clinical services are available to monitor these patients and respond to any clinical deterioration. METHODS: A cost analysis was modelled using decision tree analysis, published cost and effectiveness parameters for ambulatory care strategies and data from the State of Victoria's hospital morbidity dataset. Two-way sensitivity analyses and Monte Carlo simulation were performed to evaluate the uncertainty of costs and outcomes associated with ambulatory care. RESULTS: The modelled cost analysis showed that cost savings for two ambulatory care strategies were ~30% compared to standard hospital care. The weighted average cost saving per episode of 'low-risk' febrile neutropenia using Strategy 1 (outpatient follow-up only) was 35% (range: 7-55%) and that for Strategy 2 (early discharge and outpatient follow-up) was 30% (range: 7-39%). Strategy 2 was more cost-effective than Strategy 1 and was deemed the more clinically favoured approach. CONCLUSION: This study outlines a cost structure for a safe and comprehensive ambulatory care program comprised of an early discharge pathway with outpatient follow-up, and promotes this as a cost effective approach to managing 'low-risk' febrile neutropenic patients.

[18F]fluorodeoxyglucose positron emission tomography scanning for staging, response assessment, and disease surveillance in patients with mantle cell lymphoma.

BACKGROUND: Positron emission tomography (PET) is an important imaging modality in the staging and response assessment of patients with lymphoma, but data on its specific use in mantle cell lymphoma (MCL) are lacking. PATIENTS AND METHODS: The records of 28 patients with MCL who had a total of 123 [18F]fluorodeoxyglucose (FDG) PET scans between March 1999 and November 2005 were reviewed. Nine patients had staging scans. The other scans were performed for response assessment or relapse surveillance. RESULTS: FDG-PET sensitivity was 100% for nodal disease in the 9 patients studied at baseline. Positron emission tomography scans performed for response assessment were concordant with conventional imaging in 47% and discordant in 53% of cases. Positron emission tomography scanning led to earlier diagnosis of relapse in 1 of 17 patients but produced a high rate of false-negative findings in the evaluation of gastrointestinal involvement. CONCLUSION: FDG-PET appears to be a sensitive modality for staging and for response assessment in MCL but was not found to be useful in relapse surveillance or in the evaluation of gastrointestinal disease.

Early therapeutic response assessment by (18)FDG-positron emission tomography during chemotherapy in patients with diffuse large B-cell lymphoma: isolated residual positivity involving bone is not usually a predictor of subsequent treatment failure.

Residual 2-fluoro-2-deoxyglucose (FDG) - positron emission tomography (PET) positivity during treatment of patients with diffuse large B-cell lymphoma (DLBLC) prospectively identifies a subgroup at high likelihood of subsequent treatment failure. A single institution clinical audit of FDG-PET performance for this indication was undertaken for patients with DLBCL treated with anthracycline-based chemotherapy +/- radiotherapy. Of 45 eligible patients, 14 (31%) were PET-positive after a median of three chemotherapy cycles (range 1 - 5), of which 10 (71%) progressed at a median of 6.5 months. An interim positive PET was a statistically significant adverse prognostic factor for treatment failure (P < 0.0001, log-rank analysis) with a hazard ratio for a positive interim-treatment PET of 9 (95% confidence interval = 4 - 55) and positive predictive value of 71% and negative predictive value of 90%. Notably, four patients with low-grade FDG-avidity limited to sites previously involved by biopsy-proven osseous lymphoma, remain progression-free (median follow-up 62 months). Low-grade FDG-avidity on interim restaging at sites of bone involvement by DLBCL at diagnosis, appears to be less predictive of disease progression than residual nodal or extra-nodal soft tissue abnormality by PET.

Cytomegalovirus DNAemia and disease: incidence, natural history and management in settings other than allogeneic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Despite increasing intensity and profound immunosuppression associated with newer therapies for hematologic malignancies, little information exists regarding cytomegalovirus (CMV) reactivation in settings other than allogeneic stem cell transplantation (SCT). DESIGN AND METHODS: We reviewed the epidemiology of CMV disease in patients who were CMV polymerase chain reaction (PCR) positive during treatment for hematologic malignancies without allogeneic SCT from June 1999 to June 2004. RESULTS: Thirty-six patients with CMV reactivation were identified. Of these, 92% were undergoing investigation for fever. Fifteen patients with CMV DNAemia were treated with ganciclovir without CMV disease developing. Notably, 20 patients with untreated CMV DNAemia did not develop CMV disease during a median follow-up of 3.5 (1-19) months. The highest rates of reactivation were observed with HyperCVAD (7.8%) and alemtuzumab (50%). INTERPRETATION AND CONCLUSIONS: We recommend that screening for CMV DNAemia be instituted and pre-emptive therapy contemplated for asymptomatic CMV reactivation only in patients receiving alemtuzumab therapy, but not routinely for other patients outside the allogeneic SCT setting. Indeed for such patients, detection of isolated CMV DNAemia does not imply the need for immediate therapy and future studies are needed to validate PCR detection of CMV DNA and CMV DNA titers as predictors for CMV disease.