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We report the results of a Phase I/II dose escalation study to determine the maximum tolerated dose (MTD) of cyclophosphamide when combined with lenalidomide and dexamethasone in relapsed/refractory myeloma. Thirty-one patients were enrolled in cohorts of 3, at five dose levels of cyclophosphamide to a maximum of 700 mg on days 1 and 8 of a 28-d cycle. Patients received lenalidomide 25 mg days 1–21 and dexamethasone 20 mg orally days 1–4 and 8–11. The MTD was 600 mg cyclophosphamide, days 1 and 8. Grade 3/4 haematological complications occurred in 26% of patients, grade 3/4 infection in 3% (both at 700 mg cyclophosphamide), with thromboembolic complications in 6% of patients. Overall complete response (CR) rate was 29%, very good partial response rate 7% and partial response rate 45% giving an overall response rate of 81%. After 21 months median follow-up, projected 2-year progression-free survival was 56%, with 80% overall survival at 30 months. Ten further patients were treated at MTD with a 40% CR rate. No dose reductions for any study drugs or deaths occurred during cycles 1–9. Lenalidomide, cyclophosphamide and dexamethasone is a safe, effective combination in relapsed myeloma inducing a high response rate, warranting further investigation in phase III trials. [ABSTRACT FROM AUTHOR]

The article examines the use Lenalidomide as an effective and tolerated regimen for myeloma patients. An oral analogue of thalidomide without neurotoxic and teratogenic side effects, Lenalidomide has been found to be more potent antitumor and immunomodulatory activity. Retrospective analysis was conducted to assess the efficacy and toxicity of the drug when combined with cyclophosphamide and dexamethasone.

A letter to the editor is presented regarding the use of bendamustine, thalidomide, and dexamethasone for multiple myeloma patients.

Background: Multiple myeloma is an incurable cancer with a rising incidence globally. Less toxic treatments are increasingly available, so patients are living longer and treatment decisions are increasingly guided by QOL concerns. There is no QOL assessment tool designed specifically for use in the clinical care of people with myeloma. This study aimed to develop and test the psychometric properties of a new myeloma-specific QOL questionnaire designed specifically for use in the clinical setting - the MyPOS. Methods: The MyPOS was developed using findings from a previously reported literature review and qualitative study. The prototype MyPOS was pretested using cognitive interviews in a purposive sample of myeloma patients and refined prior to field testing. The psychometric properties of the MyPOS were evaluated in a multi-centre, cross sectional survey of myeloma patients recruited from 14 hospital trusts across England. Results: The prototype MyPOS contained 33 structured and open questions. These were refined using cognitive interviews with 12 patients, and the final MyPOS contained 30 items taken forward for field-testing. The cross-sectional survey recruited 380 patients for the MyPOS validation. Mean time to complete was 7 minutes 19 seconds with 0.58% missing MyPOS items overall. Internal consistency was high (α = 0.89). Factor analysis confirmed three subscales: Symptoms & Function; Emotional Response and Healthcare Support. MyPOS total scores were higher (worse QOL) in those with active disease compared to those in the stable or plateau phase (F = 11.89, p < 0.001) and were worse in those currently receiving chemotherapy (t = 3.42, p = 0.001). Scores in the Symptoms & Function subscale were higher (worse QOL) in those with worse ECOG performance status (F = 31.33, p < 0.001). Good convergent and discriminant validity were demonstrated. Conclusions: The MyPOS is the first myeloma-specific QOL questionnaire designed specifically for use in the clinical setting. The MyPOS is based on qualitative enquiry and the issues most important to patients. It is a brief, comprehensive and acceptable tool that is reliable and valid on psychometric testing. The MyPOS can now be used to support clinical decision making in the routine care of myeloma patients. [ABSTRACT FROM AUTHOR]

PADIMAC trial Multiple myeloma, autologous stem cell transplantation, high dose therapy, myeloma therapy Keywords: multiple myeloma; autologous stem cell transplantation; high dose therapy; myeloma therapy EN multiple myeloma autologous stem cell transplantation high dose therapy myeloma therapy e33 e37 5 02/14/22 20220215 NES 220215 Current Phase III trials demonstrate the benefit of up-front autologous stem cell transplant (ASCT) as standard of care for transplant-eligible newly diagnosed patients with multiple myeloma.1-3 Deeper responses and achievement of minimal residual disease (MRD) negativity with current triplet and quadruplet treatments4 has questioned timing and role of ASCT with deferral being preferable for some.5,6 Long-term analysis of the EMN02 trial shows that high-risk patients gain most survival benefit from up-front ASCT3 and such risk-stratified approach to ASCT with standard risk patients receiving deferred ASCT, may be acceptable.7 We previously reported primary results of the Phase II PADIMAC trial, which demonstrated a median progression-free survival (PFS) of 17-0 months [95% confidence interval (CI): 10-5-23-2] for 63 patients who achieved a very good partial response (VGPR) or better post induction and stopped treatment until disease progression.8 MRD-positive patients at day 100 had a median PFS of 9-9 months (95% CI: 5-8-23-2) compared to 24-8 months (95% CI: 18-3-34-2) for MRD-negative patients. [Extracted from the article]

Keywords: Castleman disease; interleukins; POEMS; KSHV/HHV8; HIV; TAFRO EN Castleman disease interleukins POEMS KSHV/HHV8 HIV TAFRO 328 337 10 11/01/21 20211101 NES 211101 Methodology This "Good Practice Paper" was compiled according to the British Society for Haematology (BSH) process at (http://www.b-s-h.org.uk/guidelines). Despite the success of IL-6-signalling blockade, there remains a significant unmet clinical need not only for patients who are intolerant of anti-IL-6 therapy, but also for a reliable disease-modifying therapy.50 Tocilizumab is a monoclonal antibody that antagonises the IL-6 receptor (IL-6R) to block signal transduction.57 Tocilizumab is licensed in Japan, but not in the UK, for the treatment of iMCD-TAFRO. Survival rates for MCD are not clear given changes in in diagnostic criteria, reporting and therapy.7 Nevertheless, the 5-year OS rate for MCD have been estimated at ˜65%.4 Human herpesvirus 8-associated MCD (HHV8-MCD) A proportion of cases of MCD have been attributed to infection with HHV8. The choice of therapy in MCD depends on the presentation of the patient as well as identification of drivers of disease: HHV8-MCD, POEMS-MCD, iMCD (NOS and TAFRO). [Extracted from the article]

High dose chemoradiotherapy with autologous peripheral blood progenitor cell transplantation (PBPCT) may improve outcome in myeloma. Melphalan is an effective drug in the treatment of myeloma, but is potentially toxic to progenitor cells. We studied 8 patients receiving intermittent intravenous melphalan (25 mg/m2) as induction therapy before PBPCT to assess engraftment characteristics post-transplantation. Comparison was made with an age-matched control group of patients with non-Hodgkins lymphoma who had not received melphalan during induction therapy. There was correlation (P=0.037) between the dose of melphalan per kg body weight given, premobilization, and days to neutrophil engraftment, but no significant difference between the two groups in neutrophil recovery. The study group had delayed platelet recovery (P=0.01) and required more platelet support post-transplantation (P=0.05). 3-4 weekly melphalan (25 mg/m2) up to 6 courses was delivered to patients who went on to PBPCT without significantly influencing neutrophil recovery but with a negative impact on platelet recovery. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple myeloma, an incurable haematological cancer, often receive palliative care only late in their trajectory. Criteria for early referral are lacking. Aim: To identify which patients might benefit from early integration, by identifying trajectories of health-related quality of life and the determinants for declining or poor Health related quality of life. Design: Prospective, longitudinal cohort study. Participants: Multiple myeloma patients at all stages (newly diagnosed, first-line or second-line treatment, early or later treatment-free interval, refractory disease) from in- and outpatient units at 14 hospitals in England were recruited. In addition to clinical information and standardised Health related quality of life and psychological aspects, the Myeloma Patient Outcome Scale (MyPOS) measured palliative care concerns. Results: A total of 238 patients were recruited, on average 3.5 years (SD : 3.4) post-diagnosis. Latent mixture growth models identified four Health related quality of life trajectories. Classes 3 and 4 represent trajectories of stable poor Health related quality of life or declining Health related quality of life over an 8-month period. The strongest predictors of poor outcome at the end of follow-up were general symptom level (odds ratio (OR): 1.3, 95% CI: 1.0–1.6, p = 0.028), presence of clinically relevant anxiety (OR: 1.2, 95% confidence interval (CI): 1.0–1.4, p = 0.019), and presence of pain (OR: 1.02, 95% CI: 1.0–1.1, p = 0.018), all being more predictive than demographic or clinical characteristics. Conclusion: General symptom level, pain and presence of anxiety predict declining Health related quality of life in multiple myeloma. Identification of patients with palliative care needs should focus on assessing patient-reported symptoms and psychosocial well-being for identifying those at risk of deterioration. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma is an incurable cancer with a rising incidence globally. Less toxic treatments are increasingly available, so patients are living longer and treatment decisions are increasingly guided by QOL concerns. There is no QOL assessment tool designed specifically for use in the clinical care of people with myeloma. This study aimed to develop and test the psychometric properties of a new myeloma-specific QOL questionnaire designed specifically for use in the clinical setting - the MyPOS. Methods: The MyPOS was developed using findings from a previously reported literature review and qualitative study. The prototype MyPOS was pretested using cognitive interviews in a purposive sample of myeloma patients and refined prior to field testing. The psychometric properties of the MyPOS were evaluated in a multi-centre, cross sectional survey of myeloma patients recruited from 14 hospital trusts across England. Results: The prototype MyPOS contained 33 structured and open questions. These were refined using cognitive interviews with 12 patients, and the final MyPOS contained 30 items taken forward for field-testing. The cross-sectional survey recruited 380 patients for the MyPOS validation. Mean time to complete was 7 minutes 19 seconds with 0.58% missing MyPOS items overall. Internal consistency was high (a=0.89). Factor analysis confirmed three subscales: Symptoms & Function; Emotional Res-ponse and Healthcare Support. MyPOS total scores were higher (worse QOL) in those with active disease compared to those in the stable or plateau phase (F=11.89, p<0.001) and were worse in those currently receiving chemotherapy (t=3.42, p=0.001). Scores in the Symptoms & Function subscale were higher (worse QOL) in those with worse ECOG performance status (F=31.33, p<0.001). Good convergent and discriminant validity were demonstrated. Conclusions: The MyPOS is the first myeloma-specific QOL questionnaire designed specifically for use in the clinical setting. The MyPOS is based on qualitative enquiry and the issues most important to patients. It is a brief, comprehensive and acceptable tool that is reliable and valid on psychometric testing. The MyPOS can now be used to support clinical decision making in the routine care of myeloma patients. [ABSTRACT FROM AUTHOR]

Objectives Multiple myeloma ( MM) is an incurable haematological disease. Due to novel agents, overall survival has improved in this group, yet there are no systematic reviews to understand the symptom profiles resulting from disease and treatment-related toxicities. We aimed to synthesise data on the prevalence of symptoms in patients with MM. Methods A systematic database and grey literature search were conducted in six databases. Random-effects meta-analysis with inverse variance weighting to pool prevalence data was performed. Results Thirty-six studies were included of which 34 studies ( N = 3023) provided data for meta-analysis. Twenty-seven distinct symptoms were reported, with the majority of studies focusing on pain ( n = 27), fatigue ( n = 19) and problems with functioning ( n = 15). The most prevalent symptoms were fatigue (98.8%, 95% CI 98.1-99.2%), pain (73%, 39.9-91.7), constipation (65.2%, 22.9-92.2) and tingling in the hands/feet with 53.4% (0.4-99.7). The most common problems were decreased physical functioning (98.9%, 98.2-99.3), decreased cognitive functioning (80.2%, 40-96.1) and financial difficulties (78.4%, 39.1-95.4). These problems were present in newly diagnosed to advanced disease stage. Conclusions Optimal quality of life and good symptom management in this incurable disease can only be achieved by routinely assessing symptoms throughout the disease trajectory. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma, the second most common haematological cancer, remains incurable. Its incidence is rising due to population ageing. Despite the impact of the disease and its treatment, not much is known on who is most in need of supportive and palliative care. This study aimed to (a) assess symptom severity, palliative care concerns and health-related quality of life (HRQOL) in patients with multiple myeloma, and (b) to determine which factors are associated with a lower quality of life. We further wanted to know (c) whether general symptom level has a stronger influence on HRQOL than disease characteristics.Methods: This multi-centre cross-sectional study sampled two cohorts of patients with multiple myeloma from 18 haematological cancer centres in the UK. The Myeloma Patient Outcome Scale (MyPOS) was used to measure symptoms and concerns. Measures of quality of life included the EORTC QLQ-C30, its myeloma module and the EuroQoL EQ-5D. Data were collected on socio-demographic, disease and treatment characteristics and phase of illness. Point prevalence of symptoms and concerns was determined. Multiple regression models quantified relationships between independent factors and the MyPOS, EORTC global quality of life item and EQ5D Index.Results: Five-hundred-fifty-seven patients, on average 3.5 years (SD: 3.4) post-diagnosis, were recruited. 18.2 % had newly diagnosed disease, 47.9 % were in a treatment-free interval and 32.7 % had relapsed/progressive disease phase. Patients reported a mean of 7.2 symptoms (SD: 3.3) out of 15 potential symptoms. The most common symptoms were pain (72 %), fatigue (88 %) and breathlessness (61 %). Those with relapsed/progressive disease reported the highest mean number of symptoms and the highest overall palliative care concerns (F = 9.56, p < 0.001). Factors associated with high palliative care concerns were a general high symptom level, presence of pain, anxiety, low physical function, younger age, and being in the advanced stages of disease.Conclusion: Patients with multiple myeloma have a high symptom burden and low HRQOL, in the advanced and the earlier stages of disease. Identification of patients in need of supportive care should focus on assessing patient-reported outcomes such as symptoms and functioning regularly in clinical practice, complementary to traditional biomedical markers. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma is an incurable haematological cancer that affects physical, psychological and social domains of quality of life (QOL). Treatment decisions are increasingly guided by QOL issues, creating a need to monitor QOL within clinical practice. The development of myeloma-specific QOL questionnaires has been limited by a paucity of research to fully characterise QOL in this group. Aims of the present study are to (1) explore the issues important to QOL from the perspective of people with multiple myeloma, and (2) explore the views of patients and clinical staff on existing QOL questionnaires and their use in clinical practice. Methods: The 'Issues Interviews' were semi-structured qualitative interviews to explore the issues important to QOL in a purposive sample of myeloma patients (n = 20). The 'Questionnaire Interviews' were semi-structured qualitative interviews in a separate purposive sample of myeloma patients (n = 20) to explore views on existing QOL questionnaires and their clinical use. Two patient focus groups (n = 7, n = 4) and a focus group of clinical staff (n = 6) complemented the semi-structured interviews. Thematic content analysis resulted in the development of a theoretical model of QOL in myeloma. Results: Main themes important to QOL were Biological Status, Treatment Factors, Symptoms Status, Activity & Participation, Emotional Status, Support Factors, Expectations, Adaptation & Coping and Spirituality. Symptoms had an indirect effect on QOL, only affecting overall QOL if they impacted upon Activity & Participation, Emotional Status or Support Factors. This indirect relationship has implications for the design of QOL questionnaires, which often focus on symptom status. Health-service factors emerged as important but are often absent from QOL questionnaires. Sexual function was important to patients and difficult for clinicians to discuss, so inclusion in clinical QOL tools may flag hidden problems and facilitate better care. Patients and staff expressed preferences for questionnaires to be no more than 2 pages long and to include a mixture of structured and open questions to focus the goals of care on what is most important to patients. Conclusion: Existing QOL questionnaires developed and validated for use in myeloma do not capture all that is important to patients and may not be well suited to clinical use. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma is an incurable haematological cancer that affects physical, psychological and social domains of quality of life (QOL). Treatment decisions are increasingly guided by QOL issues, creating a need to monitor QOL within clinical practice. The development of myeloma-specific QOL questionnaires has been limited by a paucity of research to fully characterise QOL in this group. Aims of the present study are to (1) explore the issues important to QOL from the perspective of people with multiple myeloma, and (2) explore the views of patients and clinical staff on existing QOL questionnaires and their use in clinical practice. Methods: The ‘Issues Interviews’ were semi-structured qualitative interviews to explore the issues important to QOL in a purposive sample of myeloma patients (n = 20). The ‘Questionnaire Interviews’ were semi-structured qualitative interviews in a separate purposive sample of myeloma patients (n = 20) to explore views on existing QOL questionnaires and their clinical use. Two patient focus groups (n = 7, n = 4) and a focus group of clinical staff (n = 6) complemented the semi-structured interviews. Thematic content analysis resulted in the development of a theoretical model of QOL in myeloma. Results: Main themes important to QOL were Biological Status, Treatment Factors, Symptoms Status, Activity & Participation, Emotional Status, Support Factors, Expectations, Adaptation & Coping and Spirituality. Symptoms had an indirect effect on QOL, only affecting overall QOL if they impacted upon Activity & Participation, Emotional Status or Support Factors. This indirect relationship has implications for the design of QOL questionnaires, which often focus on symptom status. Health-service factors emerged as important but are often absent from QOL questionnaires. Sexual function was important to patients and difficult for clinicians to discuss, so inclusion in clinical QOL tools may flag hidden problems and facilitate better care. Patients and staff expressed preferences for questionnaires to be no more than 2 pages long and to include a mixture of structured and open questions to focus the goals of care on what is most important to patients. Conclusion: Existing QOL questionnaires developed and validated for use in myeloma do not capture all that is important to patients and may not be well suited to clinical use. [ABSTRACT FROM AUTHOR]

Summary: Background: Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide. Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma, but synergistic effects have been noted when combined with dexamethasone. We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients. Methods: This multicentre, open-label, randomised phase 3 trial was undertaken in Australia, Canada, Europe, Russia, and the USA. Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma, and had failed at least two previous treatments of bortezomib and lenalidomide. They were assigned in a 2:1 ratio with a validated interactive voice and internet response system to either 28 day cycles of pomalidomide (4 mg/day on days 1–21, orally) plus low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally) or high-dose dexamethasone (40 mg/day on days 1–4, 9–12, and 17–20, orally) until disease progression or unacceptable toxicity. Stratification factors were age (≤75 years vs >75 years), disease population (refractory vs relapsed and refractory vs bortezomib intolerant), and number of previous treatments (two vs more than two). The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01311687, and with EudraCT, number 2010-019820-30. Findings: The accrual for the study has been completed and the analyses are presented. 302 patients were randomly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone. After a median follow-up of 10·0 months (IQR 7·2–13·2), median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months (95% CI 3·6–4·7) versus 1·9 months (1·9–2·2) with high-dose dexamethasone (hazard ratio 0·48 [95% CI 0·39–0·60]; p<0·0001). The most common grade 3–4 haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia (143 [48%] of 300 vs 24 [16%] of 150, respectively), anaemia (99 [33%] vs 55 [37%], respectively), and thrombocytopenia (67 [22%] vs 39 [26%], respectively). Grade 3–4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia (38 [13%] vs 12 [8%], respectively), bone pain (21 [7%] vs seven [5%], respectively), and fatigue (16 [5%] vs nine [6%], respectively). There were 11 (4%) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven (5%) in the high-dose dexamethasone group. Interpretation: Pomalidomide plus low-dose dexamethasone, an oral regimen, could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma. Funding: Celgene Corporation. [ABSTRACT FROM AUTHOR]

Introduction Treatment advances in multiple myeloma have increased expected survival from months to years for some patients. Alongside improved survival emerges a need to better understand and measure health-related quality of life ( HRQOL), both in research and clinical settings. Objectives (i) Identify HRQOL tools validated for use in myeloma; (ii) identify issues important to HRQOL from the point of view of patients with myeloma; (iii) describe the measurement properties of each HRQOL tool; (iv) evaluate the content validity of HRQOL tools in terms of their ability to capture all issues important to patients and (v) explore the suitability of each HRQOL tool for use in different settings. Method Systematic literature review of six databases with no limits by date or language. Results Thirty-nine studies reported validation of 13 HRQOL instruments. Seven studies identified issues important to HRQOL from the patients' perspective. No instrument was comprehensive to all issues important to patients. The EORTC- QLQ-C30 and MY24 have undergone the most comprehensive psychometric validation. Most validation occurred in trial patients and not clinically representative groups. No studies evaluated clinical utility of tools alongside routine practice. Conclusion The best existing HRQOL tools are designed predominantly for use in research. Reliable, valid and responsive tools exist for this purpose, but may miss issues important to patients. The design of HRQOL measures should be guided by intended utility, whether for research or clinical practice, and further validation of HRQOL tools in clinically representative groups is needed. Development and validation of HRQOL tools for clinical use may be of value. [ABSTRACT FROM AUTHOR]

The response of the tumour microenvironment to anti-cancer drugs can influence treatment efficacy. Current drug-screening methodologies fail to distinguish and quantify simultaneously the concomitant effect of drugs on the tumour stroma and cancer cells. To overcome this limitation we have developed a fluorescence-based experimental model that employs m Cherry-labelled stromal cells (e.g. bone marrow fibroblastic stromal cells) co-cultured in direct contact with enhanced green fluorescent protein-labelled tumour cell lines for accurate assessment of proliferation and viability in both cell compartments and adhesion of tumour cells. Additionally, we used fluorescence-based image analysis to determine morphological changes that correlate with cell function (e.g. morphology of the actin cytoskeleton and nuclearity of osteoclasts to predict their bone resorption activity). Using this platform we have revealed that dexamethasone induces HS5 fibroblast proliferation and contact with multiple myeloma cells via a process involving Src/c- Abl kinases. Osteoclasts also inhibited dexamethasone-induced apoptosis in myeloma cells while retaining their normal morphology and functionality in bone resorption. Myeloma resistance to dexamethasone mediated by HS5 cells and osteoclasts was reversed by treatment with the Src/c- Abl inhibitor dasatinib but not with bortezomib. This new experimental platform provides a more precise screening of new therapeutics for improved efficacy of tumour cell killing within the bone marrow microenvironment. [ABSTRACT FROM AUTHOR]

We previously reported that daily dose pomalidomide (CC-4047), a thalidomide analogue, has excellent anti-myeloma activity but is associated with myelosuppression and deep vein thrombosis. We report here a phase 1 study to determine the maximum tolerated dose (MTD) of pomalidomide at 1 mg, 2 mg, 5 mg and 10 mg on alternate days (ad). Twenty patients with relapsed myeloma were treated. Grade 4 neutropenia occurred in all patients receiving 10 mg and the MTD was defined as 5 mg ad. No thrombotic events were observed. Pomalidomide was continued following the 4-week MTD study in 17/20 patients for a median of 14 months. 10% of patients had a complete response and >50% reduction in paraprotein was achieved in 50% of subjects. Progression-free survival was 10·5 months and median overall survival was 33 months. A significant rise was observed in the proportion of CD8+ cells. Alternate day pomalidomide was associated with a marked reduction in the incidence of thrombosis whilst maintaining excellent anti-myeloma activity. This trial provides further in vivo evidence that pomalidomide modulates the immune system in myeloma patients. Phase 2 studies to further assess the optimal schedule of administration and anti-myeloma activity of this agent are planned. [ABSTRACT FROM AUTHOR]

Abstract: A major limitation to the treatment of multiple myeloma by the thalidomide analogue CC-4047 (Actimid™) is the development of a severe neutropenia. We investigated the hypothesis that this effect may have been due to CC-4047 enhancing the removal of neutrophils from the circulation by altering the expression of surface adhesion molecules required for endothelial binding, by binding to platelets, or by enhancing apoptosis. Flow cytometric analysis was used to examine the expression of neutrophil surface molecules, platelet binding and apoptosis in whole blood samples from 19 patients with multiple myeloma who were assigned to receive either 1, 2, 5 or 10 mg of CC-4047 every other day (e.o.d.) for 28 days. CC-4047 induced dose-related decreases in neutrophil numbers and increases in the percentage of CD64-positive neutrophils, but had little, or no effect on the expression of CD11b, CD62L or CD162, neutrophil-platelet binding, or apoptosis. Relative decreases in the neutrophil count were inversely associated with relative increases in the intensity of CD64 expression on neutrophils (r =− 0.307; p =0.028). Although seven patients developed severe neutropenia, none suffered severe or recurrent bacterial infections. The percentage of CD64-positive neutrophils was still increased in eight patients who continued receiving 1–5 mg CC-4047 e.o.d. for several months afterwards, but neutrophil counts were similar to pre-treatment values. [Copyright &y& Elsevier]

Fluconazole is widely used as antifungal prophylaxis but it is ineffective against Aspergillus. Itraconazole has a broader spectrum of activity but the capsules give erratic bioavailability in neutropenic patients. We compared itraconazole oral solution (which has an improved pharmacokinetic profile) with fluconazole for antifungal prophylaxis. Adults with haematological malignancies receiving chemotherapy or bone marrow transplants were randomly allocated 5 mg/kg/d itraconazole (itra) solution (288 episodes) or 100 mg fluconazole suspension (flu) (293 episodes) from before the onset of neutropenia until neutrophil recovery or suspected fungal infection. Outcomes were assessed by independent reviewers unaware of the prophylaxis allocation. More proven systemic fungal infections occurred in flu (Aspergillus four, Candida tropicalis one, C. krusei one) than itra (C. albicans one) and more of these were fatal (four versus nil). This difference reached statistical significance when first study episodes were considered separately (six flu versus nil itra, P = 0.03). Significantly more deaths of presumed fungal origin occurred in flu than itra (seven versus nil, P = 0.024). There were significantly more cases of proven aspergillosis in flu than itra (six versus nil, P = 0.038, 5/6 cases were fatal) if those occurring outside the study period are included. Significantly more patients receiving flu required amphotericin B (58 v 39, P = 0.043) but this may have been affected by the fact that the study was not blinded. There were 11 proven mucosal candidal infections in flu and four in itra. Itraconazole solution and fluconazole provide effective prophylaxis against Candida but itraconazole affords greater protection against fatal aspergillosis. [ABSTRACT FROM AUTHOR]

The article focuses on combination therapy of rituximab and thalidomide for multiple castleman disease (MCD), similar to lymphoma. 11 patients with MCD were given rituximab and thalidomide combination therapy during a study followed by thalidomide. The combination therapy induced durable and significant outcomes in majority of the patients without the need for exposure to chemotherapy.

The article discusses the effectiveness of bendamustine, thalidomide, and dexamethasone as therapy for myeloma patients with end stage renal disease. It states that myeloma patients experience renal impairment which needs to be treated by a combination of drugs that are clinically proven for their effectiveness. It discusses clinical trials, myeloma, and renal failure.

Background: Multiple myeloma is an incurable haematological cancer that affects physical, psychological and social domains of quality of life (QOL). Treatment decisions are increasingly guided by QOL issues, creating a need to monitor QOL within clinical practice. The development of myeloma-specific QOL questionnaires has been limited by a paucity of research to fully characterise QOL in this group. Aims of the present study are to (1) explore the issues important to QOL from the perspective of people with multiple myeloma, and (2) explore the views of patients and clinical staff on existing QOL questionnaires and their use in clinical practice.Methods: The 'Issues Interviews' were semi-structured qualitative interviews to explore the issues important to QOL in a purposive sample of myeloma patients (n = 20). The 'Questionnaire Interviews' were semi-structured qualitative interviews in a separate purposive sample of myeloma patients (n = 20) to explore views on existing QOL questionnaires and their clinical use. Two patient focus groups (n = 7, n = 4) and a focus group of clinical staff (n = 6) complemented the semi-structured interviews. Thematic content analysis resulted in the development of a theoretical model of QOL in myeloma.Results: Main themes important to QOL were Biological Status, Treatment Factors, Symptoms Status, Activity & Participation, Emotional Status, Support Factors, Expectations, Adaptation & Coping and Spirituality. Symptoms had an indirect effect on QOL, only affecting overall QOL if they impacted upon Activity & Participation, Emotional Status or Support Factors. This indirect relationship has implications for the design of QOL questionnaires, which often focus on symptom status. Health-service factors emerged as important but are often absent from QOL questionnaires. Sexual function was important to patients and difficult for clinicians to discuss, so inclusion in clinical QOL tools may flag hidden problems and facilitate better care. Patients and staff expressed preferences for questionnaires to be no more than 2 pages long and to include a mixture of structured and open questions to focus the goals of care on what is most important to patients.Conclusion: Existing QOL questionnaires developed and validated for use in myeloma do not capture all that is important to patients and may not be well suited to clinical use. [ABSTRACT FROM AUTHOR]