Social determinants and health‐related dimensions of quality of life in adult patients with haemophilia

The availability of safe and effective factor replacement therapies, in persons with haemophilia (PWH), has in some countries answered the basic need for treatment of these patients. The findings suggest that adult patients who have always been on prophylaxis reported significantly better physical functioning, and thus better quality of life. This study is designed to evaluate the QoL in adult PWH, by focusing on social determinants of QoL and their relationship with health‐related dimensions, in Tabriz, Iran. The survey instrument was a self‐report 36 items questionnaire, ‘A36 Hemofilia – QoL’, which is a disease‐specific questionnaire for the assessment of the health‐related QoL in adults living with haemophilia. A total of 100 haemophilia A and B patients, aged over 17 years participated in this study within 1 year. QoL total score was 71.88 (±26.89 SD). Patients who treat in our Hemophilia Treatment Center, had better QoL score (P = 0.000), and education has a significant impact on the social aspects of QoL (P = 0.18). The QoL was very poor in urban area in contrast to patients who lived in the city (54.45 vs. 74.21 respectively). Single patients have a better QoL than married patients (76.56 vs. 68.50 respectively). Our results showed that low education and lack of awareness of the diseases among PWH lead to reduce of QoL and more disease complications. More and wider treatment and psychological care for improving quality of life of these patients are seriously recommended.     

Phase I/II trial assessing bendamustine plus bortezomib combination therapy for the treatment of patients with relapsed or refractory multiple myeloma

Bendamustine, active in multiple myeloma (MM), is a bifunctional mechlorethamine derivative with alkylating properties. Bortezomib, approved to treat MM, is effective in combination with alkylators. The tolerability and efficacy of bendamustine plus bortezomib in relapsed/refractory MM was assessed in an open‐label, dose‐escalating, phase I/II study. Patients aged ≥18 years received intravenous bendamustine 50, 70, or 90 mg/m² (days 1 and 4) plus bortezomib 1·0 mg/m² (days 1, 4, 8, and 11) for up to eight 28‐day cycles. No dose‐limiting toxicity was observed after cycle 1; bendamustine 90 mg/m² plus bortezomib 1·0 mg/m² was designated the maximum tolerated dose (MTD). The most common grade 3/4 adverse events were leucopenia (58%), neutropenia (50%), lymphopenia (45%), and thrombocytopenia (30%). Primary efficacy measure was overall response rate (ORR), which was the combined complete response (CR), very good partial response (VGPR), partial response (PR), and minimal response (MR). ORR was 48% (one CR, two VGPR, nine PR, and seven MR) for all 40 enrolled patients, 52% (16/31) at the MTD (90 mg/m²), and 42% and 46% for prior use of bortezomib (n = 31) or alkylators (n = 28) respectively. Bendamustine plus bortezomib was well tolerated with promising efficacy in this heavily pretreated population.     

Prevalence,severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher‐risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher‐risk MDS patients. Pre‐treatment patient‐reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2–4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient‐reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue.     

Multiple myeloma: chemotherapy or transplantation in the era of new drugs

Objective: To review the current results of studies incorporating novel agents in multiple myeloma (MM) and discuss the role of autologous stem‐cell transplantation (ASCT) in the era of new active drugs for the treatment of this disease. The outlook for patients with symptomatic MM is changing with the introduction of bortezomib, thalidomide, and lenalidomide into the repertoire of available chemotherapeutic agents. Compared with standard chemotherapy, a survival benefit has been reported for the first time in 30 yrs. Methods: Articles published in English between 1969 and 2008 were identified by searching PubMed for ‘myeloma’, ‘diagnosis’, ‘thalidomide’, ‘bortezomib’, ‘lenalidomide’, ‘dexamethasone’, ‘prednisone’, ‘doxorubicin’, ‘cyclophosphamide’, ‘melphalan’, ‘combination chemotherapy’, and ‘autologous transplantation’. Results: In randomized studies, bortezomib, thalidomide, and lenalidomide have each been combined with dexamethasone, alkylating agents, or doxorubicin, and such combinations resulted in significant improvement in progression‐free survival. Conclusions: The incorporation of new drugs as induction therapy along with ASCT appears to produce very good partial response rates, slightly superior to those achieved by conventional chemotherapy with new drugs. How to best optimize induction, consolidation, and maintenance therapy and how to best select and prepare patients for ASCT are still to be determined. Randomized trials are needed to directly compare the current best chemotherapeutic approach with best ASCT strategies and to guide clinical practice for patients with MM.     

Front‐line,dose‐escalated immunochemotherapy is associated with a significant progression‐free survival advantage in patients with double‐hit lymphomas: a systematic review and meta‐analysis

‘Double‐hit lymphomas’ (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard‐risk, diffuse large B‐cell lymphomas (DLBCL). Consequently, dose‐intensive (DI) therapies and/or consolidation with high‐dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta‐analysis compared survival outcomes in DHL patients receiving dose‐escalated regimens [DI: R‐Hyper‐CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R‐CODOX‐M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediate‐dose: R‐EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard‐dose regimens (R‐CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the first‐line setting. Data were synthesized to estimate hazard ratios of dose‐escalated treatments versus R‐CHOP using a Weibull proportional hazards model within a Bayesian meta‐analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front‐line R‐CHOP (n = 180), R‐EPOCH (n = 91), or R‐Hyper‐CVAD/rituximab, methotrexate, cytarabine (R‐M/C), R‐CODOX‐M/R‐IVAC (DI) (n = 123). Our meta‐analysis revealed that median progression‐free survival (n = 350) for the R‐CHOP, R‐EPOCH and DI groups was 12·1, 22·2, and 18·9 months, respectively. First‐line treatment with R‐EPOCH significantly reduced the risk of a progression compared with R‐CHOP (relative risk reduction of 34%; P = 0·032); however, overall survival (n = 374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary.     

Dental health and oral health‐related quality of life in children with congenital bleeding disorders

The purpose of this study was to investigate the dental and some other aspects of oral health status of young patients with congenital bleeding disorders (CBD) and the impact of these on their quality of life (OHR‐QoL) compared with controls. DMFS‐dmfs (Decayed, Missed, Filled Tooth surfaces in permanent and primary teeth) scores, Simplified oral hygiene index, occurance of hypoplasia of first permanent molars, Temporomandibular joint dysfunction and occlusion of 46 CBD patients at the age range of 2–15 years and 46 of other children as control were compared, and the impact of their oral health situation on quality of life was also investigated. Data were analysed by chi–square, t‐test and Pearson correlation. Patients were significantly more caries‐free with less decayed teeth in primary‐permanent dentition (P = 0.03, t = ?2.17).The mean scores of OHR‐QoL of CBD patients and controls were not significantly different. Oral Bleeding was the significant variable in relation to ‘oral health‐related quality of life’ in CBD groups (Pearson correlation, r = ?0.56, P = 0.000). OHR‐QoL in the control group was related to dmfs score (r = ?0.392, P = 0.011) and male gender (r = ?0.329, P = 0.026). Congenital bleeding disorder CBD patients were found to have a better dental health situation in primary dentition compared with controls; however, their ‘oral health‐related quality of life’ was similar. Oral bleeding was the only significant factor related to OHR‐QoL in CBD. It shows an overall importance of development of comprehensive care centres for CBD as the main cause of this achievement.     

Trajectories of quality of life recovery and symptom burden after autologous hematopoietic cell transplantation in multiple myeloma

Early autologous hematopoietic cell transplantation (AHCT) with post-transplant maintenance therapy is standard of care in multiple myeloma (MM). While short-term quality of life (QOL) deterioration after AHCT is known, the long-term trajectories and symptom burden after transplantation are largely unknown. Toward this goal, a secondary analysis of QOL data of the BMT CTN 0702, a randomized controlled trial comparing outcomes of three treatment interventions after a single AHCT (N = 758), was conducted. FACT-BMT scores up to 4 years post-AHCT were analyzed. Symptom burden was studied using responses to 17 individual symptoms dichotomized as ‘none/mild’ for scores 0–2 and ‘moderate/severe’ for scores of 3 or 4. Patients with no moderate/severe symptom ratings were considered to have low symptom burden at 1-year. Mean age at enrollment was 55.5 years with 17% African Americans. Median follow-up was 6 years (range, 0.4–8.5 years). FACT-BMT scores improved between enrollment and 1-year and remained stable thereafter. Low symptom burden was reported by 27% of patients at baseline, 38% at 1-year, and 32% at 4 years post-AHCT. Predictors of low symptom burden at 1-year included low symptom burden at baseline: OR 2.7 (1.8–4.1), p < 0.0001; older age: OR 2.1 (1.3–3.2), p = 0.0007; and was related to being employed: OR 2.1 (1.4–3.2), p = 0.0004). We conclude that MM survivors who achieve disease control after AHCT have excellent recovery of FACT-BMT and subscale scores to population norms by 1-year post-transplant, though many patients continue to report moderate to severe severity in some symptoms at 1-year and beyond.     

Effects of single‐agent bortezomib as post‐transplant consolidation therapy on multiple myeloma‐related bone disease: a randomized phase II study

This phase II study explored the effects of bortezomib consolidation versus observation on myeloma‐related bone disease in patients who had a partial response or better after frontline high‐dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35‐day cycles of bortezomib 1·6 mg/m² intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent‐to‐treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End‐of‐treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression‐free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.     

Response to pretransplant hypomethylating agents influences the outcome of allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic syndromes

This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome (MDS) according to their response to hypomethylating agents (HMA). While 2‐yr disease‐free survival (DFS) of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of the remaining patients with MDS according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G‐COR (group of continuous response, n = 19), G‐NoC (group of no change, n = 15), G‐LOR (group of loss of response, n = 6), and G‐DP (group of disease progression, n = 4), respectively. When dichotomized as G‐COR/G‐NoC versus G‐LOR/G‐DP, significantly different 2‐yr DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G‐LOR/G‐DP [hazard ratio (HR), 3.91; P = 0.008] and poor karyotype at transplantation (HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G‐LOR/G‐DP was for relapse (HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher‐risk MDS (HrMDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G‐COR showed a trend of better DFS compared with G‐NoC among HrMDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on hematopoietic stem cell transplantation (HSCT) outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for HrMDS.     

Community‐acquired respiratory virus lower respiratory tract disease in allogeneic stem cell transplantation recipient: Risk factors and mortality from pulmonary virus‐bacterial mixed infections

Risk factors (RFs) and mortality data of community‐acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co‐infections in the setting of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo‐HSCT recipients diagnosed of CARVs LRTD mono‐infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co‐infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono‐infection (n = 19, group 5). Overall survival (OS) at day 60 after bronchoalveolar lavage (BAL) was significantly higher in group 1, 2, and 4 compared to group 3 (77%, 67%, and 73% vs 35%, respectively, P = .012). Recipients of group 5 showed a trend to better OS compared to those of group 3 (62% vs 35%, P = .1). Multivariate analyses showed bacterial co‐infection as a RF for mortality (hazard ratio[HR] 2.65, 95% C.I. 1.2‐6.9, P = .017). We identified other 3 RFs for mortality: lymphocyte count <0.5 × 10⁹/L (HR 2.6, 95% 1.1‐6.2, P = .026), the occurrence of and CMV DNAemia requiring antiviral therapy (CMV‐DNAemia‐RAT) at the time of BAL (HR 2.32, 95% C.I. 1.1‐4.9, P = .03), and the need of oxygen support (HR 8.3, 95% C.I. 2.9‐35.3, P = .004). CARV LRTD co‐infections are frequent and may have a negative effect in the outcome, in particular in the context of bacterial co‐infections.     

Physical and mental quality of life in adult patients with haemophilia in Belgium: the impact of financial issues

In Belgium, where haemophilia affects approximately 1:7000 people (2011), data on patients' quality of life (QoL) is scarce. This project aims to assess physical and mental QoL (P‐QoL and M‐QoL) simultaneously, and to analyse the influence of different variables on these two aspects of QoL. After Ethics Committee approval, we contacted 84 adult haemophilia A (HA) and haemophilia B (HB) patients, without current inhibitors, on replacement therapy (on‐demand or secondary prophylaxis), regularly followed up at our comprehensive treatment centre. Seventy‐one (n = 59 HA, n = 12 HB) replied to our questionnaire, which included the SF36v2 QoL assessment forms. We analysed two groups of variables: one including variables previously associated with decreased QoL, and another including variables with unclear impact on QoL (e.g. patients' understanding of haemophilia‐related issues, economical concerns). In our population (mean ± SD age: 45.2 ± 14.7 years old), P‐QoL appeared more reduced than M‐QoL. P‐QoL was strongly influenced by the number of arthropathies while M‐QoL was primarily affected by patients' concern of personal costs due to haemophilia. Among this latter group, having knowledge of insurance coverage had a positive impact on M‐QoL. Scores did not depend on haemophilia type. QoL was impaired in our haemophilia patients. A simultaneous assessment of P‐QoL and M‐QoL confirmed the benefit of primary prophylaxis in P‐QoL, while originally pointing out the major burden of patients' concerns and poor understanding of haemophilia‐related economical issues on their M‐QoL. This might become a particularly challenging issue in times of financial crisis.     

Bortezomib‐Cyclophosphamide‐Dexamethasone (VCD) versus Bortezomib‐Thalidomide‐Dexamethasone (VTD) ‐based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta‐analysis

Three‐drug induction regimens have become the standard of care in newly diagnosed transplant‐eligible multiple myeloma patients. Two frequently used protocols are bortezomib, cyclophosphamide and dexamethasone (VCD) and bortezomib, thalidomide and dexamethasone (VTD). Comparisons between the two are lacking. The present study aimed to identify the differences in response rate and toxicity between the two regimens. Databases were searched using the terms ‘VTD’ or ‘VCD’ and ‘induction regimens for newly diagnosed multiple myeloma’. Prospective trials evaluating initial response in transplant eligible patients were included. The main outcome measures were response rates and adverse events. Eight clinical trials were eligible for analysis. Overall 672 patients were treated with either VCD (n = 157) or VTD (n = 515) as induction therapy. Patients treated with VTD presented with a significantly higher complete/near complete response (34% vs. 6%, P = 0·002) as well as a higher very good partial response rate or better, following induction therapy (62% vs. 27%, P < 0·0001). Although grade 3–4 neurotoxicity was more frequent during VTD therapy (11% vs. 6%, P = 0·057), a higher incidence of overall grade 3–4 adverse events was found in the VCD‐treated patients (74% vs. 51%, P < 0·001). VTD induction therapy may be superior in achieving deeper response rate following induction therapy, and is better tolerated.     

Significance of baseline and change in quality of life scores in predicting clinical outcomes in an international phase III trial of advanced pancreatic cancer: NCIC CTG PA.3

BackgroundThere is insufficient information regarding the prognostic significance of baseline and change in quality of life (QoL) scores on overall survival (OS) in advanced pancreatic cancer.MethodsQoL was assessed prospectively using the EORTC QLQ-C30 as part of the PA.3 trial of gemcitabine + erlotinib (G + E) vs. gemcitabine + placebo (G + P). Relevant variables and QoL scores at baseline and change at 8 weeks were analyzed by Cox stepwise regression to determine predictors of OS.Results222 of 285 patients (pts) treated with G + E and 220 of 284 pts treated with G + P completed baseline QoL assessments. In a multivariable Cox analysis combining all pts, better QoL physical functioning (PF) score independently predicted longer OS (HR 0.86; CI: 0.80–0.93), as did non-white race (HR 0.64; CI: 0.44–0.95), PS 0–1 (HR 0.65; CI: 0.50–0.85), locally advanced disease (HR 0.55; CI: 0.43–0.71) and G + E (HR 0.78; CI: 0.64–0.96). Improvement in physical function at week 8 also predicted for improved survival (HR 0.89; CI: 0.81–0.97 for 10 point increase in score, p = 0.02).ConclusionIn addition to clinical variables, patient reported QoL scores at baseline and change from baseline to week 8 added incremental predictive information regarding survival for advanced pancreatic cancer patients.     

Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma

The proteasome inhibitor, bortezomib, potentially increases cell sensitivity to chemotherapy. This study was performed to determine the overall response rate (ORR), overall survival (OS), progression‐free survival (PFS) and toxicity of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) compared to CHOP + bortezomib chemotherapy in mantle cell lymphoma (MCL) patients at first relapse. Forty‐six patients were randomly assigned to standard dose CHOP ± bortezomib 1·6 mg/m² given on a 21‐d cycle for up to eight cycles of treatment. Median age was 71 years (CHOP arm) and 69 years (CHOP‐bortezomib arm). Median Eastern Cooperative Oncology Group performance status was 1 (CHOP) and 0 (CHOP‐bortezomib) with 65% and 52%, respectively, having a disease stage of IV. ORR was 47·8% (CHOP) and 82·6% (CHOP‐bortezomib). Complete response rate was 21·7% (CHOP) vs. 34·8% (CHOP‐bortezomib); partial response rate was 26·1% (CHOP) vs. 47·8% (CHOP‐bortezomib). Median OS was 11·8 months (CHOP) and 35·6 months (CHOP‐bortezomib) (P = 0·01, Hazard ratio [HR] 0·37 [95% confidence interval (CI) 0·16–0·83)] and there was a non‐significant improvement in PFS: 8·1 months (CHOP) and 16·5 months (CHOP‐bortezomib) [P = 0·12, HR 0·60 (95% CI 0·31–1·15)]. Severe (≥grade 3) sensory neuropathy was similar in both arms (4·3% CHOP vs. 6·5% CHOP‐bortezomib). We conclude that the addition of bortezomib to CHOP chemotherapy for relapsed MCL significantly improves outcome with a manageable increase in toxicity.     

Health-related quality of life in adults with transfusion-independent thalassaemia intermedia compared to regularly transfused thalassaemia major: new insights

Background: In patients with β thalassaemia intermedia (TI), the milder anaemia and transfusion independence imply better health‐related quality of life (HR‐QoL). However, the unbalanced pathophysiology of the disease allows for several serious clinical complications to manifest, which may have a negative impact on HR‐QoL. Methods: This was a cross‐sectional study on adult patients with transfusion‐ and iron chelation‐independent TI and β thalassaemia major (TM) attending the Chronic Care Center, Hazmieh, Lebanon. A total of 80 patients agreed to participate in the study [32 TI (median age 24 yr) and 48 TM (median age 23 yr)]. The RAND SF‐36 survey was used to assess HR‐QoL. Data on patient demographics, clinical complications and socioeconomic status were collected. Results: Patients with TI and TM were comparable with age and gender, but patients with TM had a significantly longer median duration with a known thalassaemia diagnosis. Patients with TI had a higher proportion of multiple complications. Socioeconomic parameters were comparable, except for patients with TI being more commonly married. The mean Total, Physical Health and Mental Health Scores were significantly lower in patients with TI compared to TM, indicating poorer HR‐QoL. There was a statistically significant positive correlation between the duration with a known thalassaemia diagnosis and a higher Mental Health Score (r_s = 0.73, P = 0.020). The mean Physical Health Score was significantly lower in patients with multiple clinical complications compared to patients with single or no complications (P = 0.012). Associations remained independently significant at multivariate analysis. Conclusion: Patients with transfusion‐independent TI have lower HR‐QoL compared to TM patients. At a comparable age, the shorter duration since diagnosis and the multiplicity of complications may explain these findings.     

Health‐related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy

Patients with myelofibrosis (MF) have significant debilitating symptoms, physical disabilities, and poor health‐related quality of life (HRQoL). Here, we report post‐hoc analyses of the impact of ruxolitinib, a potent and selective JAK1 and JAK2 inhibitor, on disease‐related symptoms and HRQoL in MF patients from the large phase 3 COMFORT‐II study (N = 219). During the follow‐up period of 48 weeks, HRQoL and MF‐associated symptoms improved from baseline for ruxolitinib‐treated patients but remained the same or worsened for best available therapy (BAT)‐treated patients. Based on the European Organization for Research and Treatment of Cancer QoL Questionnaire core 30 items (EORTC QLQ‐C30), treatment‐induced differences in physical and role functioning, fatigue, and appetite loss significantly favoured ruxolitinib versus BAT from week 8 (P < 0·05) up to week 48 (P < 0·05). Ruxolitinib resulted in significantly higher response rates in global health status/QoL and Functional Assessment of Cancer Therapy‐Lymphoma (FACT‐Lym) summary scores versus BAT at most time points (P < 0·05). Significant improvements in the Lymphoma subscale (including symptoms of pain, fever, itching, fatigue, weight loss, loss of appetite, and other patient concerns), FACT‐General, FACT‐Lym trial outcome index, and FACT‐Lym total were also observed with ruxolitinib versus BAT starting at week 8 and continuing thereafter. Overall, these data demonstrated that ruxolitinib improved HRQoL in MF patients and further support the use of ruxolitinib for the treatment of symptomatic MF.     

The proteasome inhibitor CEP‐18770 enhances the anti‐myeloma activity of bortezomib and melphalan

The anti‐multiple myeloma (MM) efficacy of bortezomib has led to the development of other proteasome inhibitors (PI), including CEP‐18770 which has shown anti‐MM effects in preclinical studies. However, the efficacy of orally (PO) or intravenously (IV) administered CEP‐18770 in multiple MM models and in combination with conventional anti‐MM therapies has not been evaluated. Herein, we show that CEP‐18770 combined with melphalan or bortezomib induces synergistic inhibition of MM cell viability in vitro. In MM xenograft models, the addition of CEP‐18770 IV to melphalan completely prevented the growth of both melphalan‐sensitive and melphalan‐resistant tumours. The combination of CEP‐18770 IV and bortezomib induced complete regression of bortezomib‐sensitive tumours and markedly delayed progression of bortezomib‐resistant tumours compared to treatment with either agent alone. Single agent CEP‐18770 PO also showed marked anti‐MM effects in these xenograft models. These studies provide strong preclinical rationale for further development of this novel PI in the treatment of MM as a monotherapy as well as combined with either melphalan or bortezomib.     

High incidence of post‐transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib‐based regimens: a survey from the Rome Transplant Network

The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post‐engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib‐based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.