Imaging in myeloma: a Royal College of Radiologists national survey of current imaging practice.

AIMS: To evaluate current national imaging practice in myeloma with reference to National Institute for Health and Care Excellence (NICE) guidelines (NG35, 2016) and compare results with an initial survey conducted in 2017 (61 participating sites). MATERIALS AND METHODS: All UK radiology departments treating myeloma patients and with a Royal College of Radiologists (RCR) Audit Lead were invited to participate. Data were collected using an online questionnaire. Descriptive statistics were performed. RESULTS: One hundred and fourteen hospitals supplied data (54% return rate). Skeletal survey (SS) remains the most-commonly performed first-line imaging test for suspected/confirmed myeloma or plasmacytoma (39%, 45/114 hospitals), followed by whole-body magnetic resonance imaging (WBMRI) (27%, 31/114) and whole-body computed tomography (WBCT) (19%, 22/114). Integrated positron-emission tomography/CT (PET/CT) was first-line in 14% (16/114). The NICE recommended initial investigation, WBMRI, is currently offered in 27% of surveyed hospitals (<10% in 2017). Ongoing challenges to implementing WBMRI include scanner availability, financial constraints, reporting time, and radiologist training. CONCLUSION: Despite NICE recommendations regarding WBMRI in diagnosis/follow-up of myeloma, SS (poor sensitivity and specificity) remains the most commonly performed first-line test. Radiologists, haematologists, and patients should continue to emphasise the superiority and benefit of modern and more accurate imaging, such that they are prioritised in clinical service planning.

Autologous stem cell transplantation for multiple myeloma patients with chronic kidney disease: a safe and effective option.

Chronic Kidney Disease (CKD) is a frequent complication in patients with multiple myeloma (MM) and is associated with adverse outcomes. The use of autologous stem cell transplantation (ASCT) has improved disease outcomes, however, the safety and efficacy of ASCT in patients with CKD has been the subject of debate. To investigate this, we conducted a retrospective analysis of 370 MM patients who underwent their first ASCT, including those with mild, moderate and severe CKD as well as normal renal function at the time of transplant. No significant difference in ASCT-related mortality, Progression-Free or Overall Survival was noted between the different renal function groups. A decline in estimated glomerular filtration rate (eGFR) at 1-year of >8.79% was associated with poorer overall survival (p < 0.001). The results of this study show that ASCT is a safe and effective option for myeloma patients with CKD, including those on dialysis. Patients who demonstrate renal deterioration at 1-year post-transplant should be closely monitored as this is a predictor for poor survival.

Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group.

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma.

PURPOSE: To assess the safety, efficacy, and immunomodulatory effects of CC-4047 (Actimid; Celgene, San Diego, CA) in patients with relapsed or refractory myeloma. PATIENTS AND METHODS: Twenty-four relapsed or refractory patients were treated with a dose-escalating regimen of oral CC-4047. Clinical responses and adverse effects were identified, and peripheral T-cell subsets, serum cytokines, and proangiogenic factors were evaluated. RESULTS: CC-4047 was tolerated with no serious nonhematologic adverse events. All patients were eligible for analysis. Toxicity criteria during the initial 4 weeks of study were used to define the maximum-tolerated dose (MTD). During this period, one patient withdrew with a deep vein thrombosis (DVT) probably caused by an undiagnosed primary melanoma with lymphadenopathy in the groin, one patient withdrew because of progressive disease (PD), and three patients discontinued with neutropenia. Nineteen of 24 patients continued on treatment beyond 4 weeks to PD or development of a serious adverse event. Three further patients developed a DVT at 4, 9, and 11 months. Treatment resulted in a greater than 25% reduction in paraprotein in 67% of patients, 13 patients (54%) experienced a greater than 50% reduction in paraprotein, and four (17%) of 24 patients entered complete remission. The MTD was 2 mg/d. All patients showed increased CD45RO expression on CD4(+) and CD8(+) cells, with a concomitant decrease in CD45RA(+) cells. CC-4047 treatment was associated with significantly increased serum interleukin (IL)-2 receptor and IL-12 levels, which is consistent with activation of T cells and monocytes and macrophages. CONCLUSION: This study demonstrates the safety and efficacy of CC-4047. The MTD of CC-4047 orally was 2 mg/d. This is the first report demonstrating in vivo T-cell costimulation by this class of compound, supporting a potential role for CC-4047 as an immunostimulatory adjuvant treatment.

Second autologous transplant with cyclosporin/interferon alpha-induced graft versus host disease for patients who have failed first-line consolidation.

The prognosis for patients with non-Hodgkin's lymphoma (NHL) and advanced Hodgkin's disease (HD) who relapse following autologous transplant is poor. We report on a pilot study designed to evaluate the feasibility of using Cyclosporin A and interferon alpha to induce autologous GVHD following a second autologous transplant for relapsed lymphoma. In all, 10 patients entered the study with median age 46.5 years. Diagnosis was NHL (n=7) or Hodgkin's lymphoma (n=3). All had relapsed from a prior autologous transplant. The second transplant was well tolerated by all patients. Histological changes consistent with cutaneous GVHD developed in 30% of patients at a median of 22.5 days from transplant and settled spontaneously in all cases. Five patients have died (four from progressive disease) at a median 7 months from second transplant. Five patients are still alive and in complete remission at a median of 20 months from transplant. Median overall survival for the group is 13.5 months and median relapse-free survival has not been reached at 42 months. This is a well-tolerated regimen for use in this poor-risk group of patients with lymphoma. The overall survival and event-free survival are encouraging, however further studies are necessary.

A parainfluenza-3 outbreak in a SCT unit: sepsis with multi-organ failure and multiple co-pathogens are associated with increased mortality.

The estimated frequency of parainfluenza virus 3 (PIV-3) infections following haematopoietic SCT (HSCT) is 2-7%, whereas reported mortality ranges from 18 to 33%. We report a retrospective outcome analysis following an outbreak of PIV-3 infection in our transplant unit. A total of 16 HSCT patients developed PIV-3 infection. All patients had upper respiratory tract infection, whereas lower respiratory tract infection occurred in 8 patients. Overall, 13 patients were treated with aerosolised Ribavirin (2 g t.d.s. for 5 days) and i.v. Ig (0.5 g/kg) as per standard protocol. One patient refused treatment, whereas two patients with full immune reconstitution were not treated. Overall mortality was 62.5%. Sepsis with multi-organ failure and the presence of pulmonary co-pathogens were both significantly associated with PIV-3-related mortality. Our series confirms that high mortality is associated with PIV-3 infection in HSCT recipients. In patients who develop PIV-3 infection, despite strict enforcement of infection control policies, the best strategy might be careful risk assessment, with effective broad-spectrum anti-microbials in those who are at risk of secondary infection.