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High-dose dexamethasone is a mainstay of therapy for multiple myeloma. We studied whether low-dose dexamethasone in combination with lenalidomide is non-inferior to and has lower toxicity than high-dose dexamethasone plus lenalidomide. Patients with untreated symptomatic myeloma were randomly assigned in this open-label non-inferiority trial to lenalidomide 25 mg on days 1–21 plus dexamethasone 40 mg on days 1–4, 9–12, and 17–20 of a 28-day cycle (high dose), or lenalidomide given on the same schedule with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle (low dose). After four cycles, patients could discontinue therapy to pursue stem-cell transplantation or continue treatment until disease progression. The primary endpoint was response rate after four cycles assessed with European Group for Blood and Bone Marrow Transplant criteria. The non-inferiority margin was an absolute difference of 15% in response rate. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00098475. 445 patients were randomly assigned: 223 to high-dose and 222 to low-dose regimens. 169 (79%) of 214 patients receiving high-dose therapy and 142 (68%) of 205 patients on low-dose therapy had complete or partial response within four cycles (odds ratio 1·75, 80% CI 1·30–2·32; p=0·008). However, at the second interim analysis at 1 year, overall survival was 96% (95% CI 94–99) in the low-dose dexamethasone group compared with 87% (82–92) in the high-dose group (p=0·0002). As a result, the trial was stopped and patients on high-dose therapy were crossed over to low-dose therapy. 117 patients (52%) on the high-dose regimen had grade three or worse toxic effects in the first 4 months, compared with 76 (35%) of the 220 on the low-dose regimen for whom toxicity data were available (p=0·0001), 12 of 222 on high dose and one of 220 on low-dose dexamethasone died in the first 4 months (p=0·003). The three most common grade three or higher toxicities were deep-vein thrombosis, 57 (26%) of 223 versus 27 (12%) of 220 (p=0·0003); infections including pneumonia, 35 (16%) of 223 versus 20 (9%) of 220 (p=0·04), and fatigue 33 (15%) of 223 versus 20 (9%) of 220 (p=0·08), respectively. Lenalidomide plus low-dose dexamethasone is associated with better short-term overall survival and with lower toxicity than lenalidomide plus high-dose dexamethasone in patients with newly diagnosed myeloma. National Cancer Institute, Rockville, MD, USA.

Previous studies have shown that socioeconomic factors play an important role in multiple myeloma (MM) health outcomes. We postulated that the type of treatment facilities and their volume of cases also affect overall survival, utilization of various therapies including palliative care services in newly diagnosed MM. Using the National Cancer Database (NCDB), we analyzed 174,551 newly diagnosed MM participants from across the country. We found that at high volume facility centers (over 90th percentile of new patient volume from 2004 to 2016), the median overall survival (OS) was 62.3 months versus 35.3 months at lower volume facilities (p <0.001). Similarly, high volume academic cancer centers had an improved median OS of 66.4 months (65.3–67.4 CI) versus 39.2 months (37.9–40.4 months CI) in lower volume academic centers (p <0.001). The odds of utilizing chemotherapy, immunotherapy, and autologous transplants were higher in academic cancer centers compared to community cancer centers, after adjusting for demographic and socioeconomic factors (OR 1.10, 1.23, and 2.06 respectively, all with p<0.001). There was significantly decreased odds of receiving palliative care (OR 0.89, 95% CI 0.85–0.93) in high volume facilities compared to low volume. Palliative care services were more frequently utilized at integrated network cancers and comprehensive community cancer centers compared to community cancer centers, with similar odds of receiving palliative care between community and academic facility types. Our results likely reflect increased provider experience and resources in higher volume and academic facilities. This highlights the need to integrate resources and improve access to community programs.

Measuring response among patients with multiple myeloma is essential for the care of patients. Deeper responses are associated with better progression free survival (PFS) and overall survival (OS). To test the hypothesis that Mass-Fix, a mass spectrometry-based means to detect monoclonal proteins, is superior to existing methodologies to predict for survival outcomes, samples from the STAMINA trial (NCT01109004), a trial comparing three transplant approaches, were employed. Samples from 575 patients from as many as three time points (post-induction [post-I; pre-maintenance [pre-M]; 1 year post enrollment [1YR]) were tested when available. Four response parameters were assessed: Mass-Fix, serum immunofixation, complete response, and measurable residual disease (MRD) by next generation flow cytometry. Of the four response measures, only MRD and Mass-Fix predicted for PFS and OS at multiple testing points on multivariate analyses. Although MRD drove Mass-Fix from the model for PFS at post-I and pre-M, 1YR Mass-Fix was independent of 1YR MRD. For OS, the only prognostic pre-I measure was Mass-Fix, and the only 1YR measures that were prognostic on multivariate analysis were 1YR MRD and 1YR Mass-Fix. SIFE and CR were not. Mass-Fix is a powerful means to track response.

The prognostic factors in autotransplanted multiple myeloma (MM) patients with concomitant advanced chronic kidney disease (CKD) are poorly understood, limited, and controversial. We retrospectively analysed 44 patients with MM and CKD (eGFR < 40 ml/min), present both at diagnosis and at autologous stem cell transplantation (ASCT), with no improvement of renal function in-between. Patients exhibiting deeper paraprotein responses to pre-transplant treatment predicted better response post ASCT (odds ratio (OR) = 11.6, = 0.028) and longer progression-free survival (PFS) (hazard ratio (HR) = 0.23, = 0.017). Higher albumin concentration (per increase of 1 g/dl) (HR = 0.41, = 0.03) and melphalan 140 mg/m versus higher melphalan doses (HR = 0.86, = 0.008) were associated with longer PFS. Performance status (ECOG 0-1 versus ≥ 2) (HR = 0.28, = 0.0036), higher albumin concentration (HR = 0.43, < 0.037), and melphalan 140 mg/m versus higher melphalan doses (HR = 0.48, = 0.081) decreased the risk of death. Three of 32 dialysis-dependent patients became dialysis independent (DID), and 5 of 12 in the DID group had eGFR improvement post ASCT. The median PFS was 2.3 years, which was shorter for DID compared to DD patients (0.7 vs. 3.3 years, respectively). The median overall survival (OS) was 3.6 years, there was no difference in median OS between the groups (4.0 vs. 3.5 years, respectively). Optimal patient selection including good performance status and higher albumin concentration (with every increase of 1 g/dl), chemotherapy-responsive disease pre-ASCT, melphalan dose adjusted to CKD, and intensive post-transplant supportive care are crucial to achieve acceptable results of treatment of MM patients with CKD.

This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.

This randomized, double-blind trial of prophylaxis to prevent invasive fungal infections was conducted in 600 patients with severe graft-versus-host disease after hematopoietic stem-cell transplantation. Posaconazole, an extended-spectrum triazole, was as effective as fluconazole in preventing invasive fungal infections (incidence, 5.3% and 9.0%, respectively). With posaconazole, there were fewer cases of invasive aspergillosis infections. In patients with severe graft-versus-host disease, posaconazole was as effective as fluconazole in preventing invasive fungal infections. With posaconazole, there were fewer cases of invasive aspergillosis infections. Invasive fungal infections remain one of the leading causes of death among recipients of hematopoietic stem-cell transplants. 1 – 3 In these patients, factors associated with complications resulting from transplantation, such as prolonged neutropenia, graft failure, immunosuppression, and graft-versus-host disease (GVHD), increase the risk of an invasive fungal infection. 4 – 6 Randomized, controlled trials have shown the superiority of fluconazole over placebo for the prevention of fungal infections, primarily those caused by candida species, after hematopoietic stem-cell transplantation. Fluconazole prophylaxis reduces both fungal-infection–related and overall mortality 7 , 8 and has become a standard of care for antifungal prophylaxis after the first 100 days of . . .

Over the past two decades, the improvement in our understanding of the biology of MM and the introduction of new drug classes, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PI), and monoclonal antibodies (MoAb), have significantly improved outcomes. The first IMiD introduced to treat MM was thalidomide. The side effects observed during treatment with thalidomide initiated work on the synthesis of IMiD analogs. Subsequently, lenalidomide and pomalidomide were developed, both with different safety profiles, and they have better tolerability than thalidomide. In 2010, the cereblon (CRBN) protein was discovered as a direct target of IMiDs. By binding to CRBN, IMiDs change the substrate specificity of the CRBN E3 ubiquitin ligase complex, which results in the breakdown of internal Ikaros and Aiolos proteins. Most clinical trials conducted, both in newly diagnosed, post-transplant maintenance and relapsed/refractory MM, report a beneficial effect of IMiDs on the extension of progression-free survival and overall survival in patients with MM. Due to side effects, thalidomide is used less frequently. Currently, lenalidomide is used at every phase of MM treatment. Lenalidomide is used in conjunction with other agents such as PIs and MoAb as induction and relapsed therapy. Pomalidomide is currently used to treat relapsed/refractory MM, also with PIs and monoclonal antibodies. Current clinical trials are evaluating the efficacy of IMiD derivatives, the CRBN E3 ligase modulators (CELMoDs). This review focuses on the impact of IMiDs for the treatment of MM.

We evaluated changes in patient‐reported outcomes and cognitive function from pre‐ to 3–6 months post‐treatment among 42 newly diagnosed patients with multiple myeloma undergoing transplant with complete data using PROMIS‐29. There were statistically significant improvements in physical (p < .001) and mental health (p < .001) but not cognition from pre‐treatment to 3–6 month follow‐up. Similar results were seen within age or comorbidity strata. Patients with myeloma undergoing transplant experienced generally improved short‐term health outcomes with no significant declines in cognition.

Multiple myeloma (MM) is a heterogeneous hematologic malignancy associated with several risk factors including genetic aberrations which impact disease response and survival. Thorough risk classification is essential to select the best clinical strategy to optimize outcomes. The SKY92 molecular signature classifies patients as standard‐ or high‐risk for progression. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) measures impact of SKY92 on risk classification and treatment plan. Newly diagnosed MM patients had bone marrow aspirates analyzed for SKY92. Physicians completed a questionnaire for each patient capturing risk classification, hypothetical treatment plan, and physician confidence in the treatment plan, before and after unblinding SKY92. One hundred forty seven MM patients were enrolled. Before unblinding SKY92, physicians regarded 74 (50%) patients as clinical standard‐risk. After unblinding SKY92, 16 patients were re‐assigned as high‐risk by the physician, and for 15 of them treatment strategy was impacted, resulting in an escalated treatment plan. For the 73 (50%) clinical high‐risk patients, SKY92 indicated 46 patients to be standard‐risk; for 31 of these patients the treatment strategy was impacted consistent with a de‐escalation of risk. Overall, SKY92 impacted treatment decisions in 37% of patients (p < 0.001). For clinical decision‐making, physicians incorporated SKY92, and the final assigned clinical risk was in line with SKY92 for 89% of patients. Furthermore, SKY92 significantly increased the confidence of the physicians’ treatment decisions (p < 0.001). This study shows potential added value of SKY92 in MM for treatment decision making.