Risk of fungal exposure in the homes of patients with hematologic malignancies.

BACKGROUND: Patients with hematological malignancies are at a high risk of developing invasive fungal infections (IFI) because they undergo several cycles of treatment leading to episodes of neutropenia. In addition, they alternate between hospital stays and periods spent at home. Thus, when an IFI is diagnosed during their hospital stays, it is highly challenging to identify the origin of the fungal contamination. The objective of this study was to analyze at home fungal exposure of 20 patients with leukemia by taking air and water samples in their living residence. METHODS: Air was sampled in 3 rooms of each home with a portable air system impactor. Tap water was collected at 3 water distribution points of each home. For positive samples, fungi were identified by mass spectrometry or on the basis of their morphological features. RESULTS: 85 % of homes revealed the presence in air of Aspergillus spp. and those belonging to the section Fumigati presented the highest concentrations and the greatest frequency of isolation. Concerning mucorales, Rhizopus spp. and Mucor spp. were isolated in air of 20 % and 5 % of dwellings, respectively. In 4 homes, more than 70 % of the fungal species identified in air were potential opportunists; these were mainly Aspergillus spp. with concentrations greater than 20 cfu/m3. The water samples revealed the presence of Fusarium in 3 dwellings, with concentrations up to 80 cfu/L. Finally, for one patient, fungal species isolated during a period of hospitalization were phenotypically similar to those isolated in samples taken at home. For a second patient, a PCR Mucorale was positive on a sample of bronchoalveolar fluid while air samples taken at his home also revealed also the presence of mucorales. CONCLUSION: The presence of opportunistic fungal species in the air of all the explored homes suggests the need for strengthened preventive measures in the home of immunocompromised patients. It would be interesting to compare the fungi isolated (from patients and from their environment) by genotyping studies aimed at specifying the correspondence existing between fungal species present in the patients' homes and those responsible for IFI in the same patients.

Early Chimeric Antigen Receptor T Cell Expansion Is Associated with Prolonged Progression-Free Survival for Patients with Relapsed/Refractory Multiple Myeloma Treated with Ide-Cel: A Retrospective Monocentric Study.

The outcomes of patients with relapsed and refractory multiple myeloma (RRMM) previously treated with the 3 main classes of myeloma therapy-immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies-remain poor. Recently, based on the phase II pivotal KarMMa trial showing prolonged overall survival (OS) and progression-free survival (PFS) in heavily treated patients, idecabtagene vicleucel (ide-cel), a B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy (CAR-T) product, was approved in the United States for the treatment of RRMM. In France, since June 2021, an early access program has authorized the use of ide-cel in the setting of RRMM (defined as progressive myeloma after at least 3 previous regimens, including the 3 main antimyeloma therapies). We report the first French experience through this early access program in a retrospective study of 24 consecutive patients treated with ide-cel at our institution. The patients were evaluated according to International Myeloma Working Group criteria and by positron emission tomography computed tomography (PET-CT) at 1, 3, 6, 9, and 12 months after ide-cel infusion. Most patients had adverse cytogenetic abnormalities, and RRMM with triple-refractory drugs were seen in 79%. Bridging therapy was required for 19 of 24 patients. Before CAR-T cell infusion, lymphodepletion with fludarabine and cyclophosphamide was systematically performed. The median follow-up was 15.2 months. At 3 months after ide-cel infusion, 92% of patients achieved at least a partial response, and 50% achieved a complete response or better (≥CR). At 6 months, 70% of patients had a persistent ≥CR. At 3 and 6 months, bone marrow minimal residual disease (10-6 level) was undetectable in 79% and 75% of patients, respectively. At 6 months, CR as assessed by PET-CT was achieved in 15 of 20 patients (75%). The median PFS was 14.8 months, and median OS was not reached. Notably, an expansion of circulating CAR-T cells to >180/mm3 after infusion was strongly associated with prolonged PFS. Additionally, the level of soluble BCMA measured before infusion was identified as a prognostic factor for PFS, likely correlated to the tumor burden. Grade 1-2 cytokine release syndrome (CRS) occurred in 22 of 24 patients (92%). Only 1 patient (4%) experienced grade ≥3 CRS. The occurrence of neurologic toxicity was infrequent (12.5%) and reversible in all cases. Hematologic toxicity was relatively common, and secondary hypogammaglobulinemia occurred in most patients. Infections (mostly viral) were frequent but most often nonsevere. This study echoes the promising results of the KarMMa trial and identifies possible prognostic indicators in RRMM patients treated with ide-cel, potentially refining treatment strategies and improving outcomes in this challenging context.

Prognostic value of postinduction medullary myeloid recovery by flow cytometry in acute myeloid leukemia.

Risk stratification and treatment response evaluation are key features in acute myeloid leukemia (AML) management. Immunophenotypic and molecular approaches all rely on the detection of persisting leukemic cells by measurable residual disease techniques. A new approach is proposed here by assessing medullary myeloid maturation by flow cytometry through a myeloid progenitor ratio (MPR). The normal MPR range was defined using reference normal bone marrows (n = 48). MPR was considered balanced if between 1 and 4 and unbalanced if < 1 or > 4. MPR was retrospectively assessed at baseline and post-induction for 206 newly diagnosed AML patients eligible for intensive treatment from two different French centers. All AML baseline MPR were unbalanced and thus significantly different from normal MPR (p < 0.0001). Patients with an unbalanced MPR after induction had worse 3-year overall survival (OS) (44.4% vs. 80.2%, HR, 2.96; 95% CI, 1.81-4.84, p < 0.0001) and 3-year relapse free survival (RFS) (38.7% vs. 64.4%, HR, 2.11; 95% CI, 1.39-3.18, p < 0.001). In multivariate analysis, postinduction unbalanced MPR was significantly associated with shorter OS and RFS regardless of the European LeukemiaNet 2010 risk stratification or NPM1/FLT3-ITD status. A balanced postinduction MPR conversely conferred favorable outcomes and reflects medullary myeloid recovery.

Low non-relapse mortality and good haematological and renal responses after autologous haematopoietic stem cell transplantation in multiple myeloma patients with renal insufficiency at transplant: A prospective Société Francophone de Greffe de Moelle-Thérapie Cellulaire observational study.

High-dose melphalan followed by autologous haematopoietic stem cell transplantation is widely used in newly diagnosed multiple myeloma (MM) patients as upfront therapy. However, the safety and efficacy of transplantation in patients with renal insufficiency (RI) are controversial. We followed a multicentre (16 SFGM-TC centres) prospective cohort of 50 newly diagnosed MM patients with a serum creatinine clearance of <40 mL/min at transplantation. Patients received a recommended dose of melphalan of 140 mg/m2. The primary end-point was the non-relapse mortality at Day 100. One death occurred during the first 100 days post-transplant. The median time to neutrophil engraftment was 12 days and to platelet engraftment was 13 days. The haematological response improved in 69% of patients, with best responses from partial response (PR) to very good partial response (VGPR) (10%), from PR to complete response (CR)/stringent complete response (sCR) (16%), from VGPR to CR/sCR (39%) and from CR to sCR (2%). At 2 years, the overall survival was 84%, the progression-free survival was 70% and the cumulative incidence of relapse was 20%. The renal response improved in 59% of patients, with the best renal responses post-transplant being minimal (9%), partial (2%) and complete (48%). Autologous transplantation was safe and effective in myeloma patients with RI at transplant.

Pomalidomide and dexamethasone until progression after first salvage therapy in multiple myeloma.

Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013-01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28-day cycles of pomalidomide 4 mg daily on days 1-21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow-up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression-free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug-related non-haematological AEs (>5%) comprised 13% infections. Long-term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response.

Upper-limb acute superficial lymphatic thrombosis: A case report.

Upper-limb acute superficial lymphatic is a rare phenomenon that has received little attention in the medical literature to date, yet it mimics superficial venous thrombosis and may also complicate a skin punch biopsy.

Safety of ninety-minute daratumumab infusion.

PURPOSE: Daratumumab is the first anti-CD38 monoclonal antibody of the class approved for recurrent and refractory multiple myeloma. Grade 3 and 4 Infusion-Related Reactions (IRRs) are frequent during the first and second infusions. Due to the risks associated with severe IRRs, daratumumab is systematically administered over a period of 3.5 hours.The main objective of this study was to evaluate the safety of a 90-minute daratumumab infusion from the third infusion. PATIENTS AND METHODS: All patients who had received two or more doses of daratumumab in monotherapy or in combination with standard infusion rates were included. We excluded patients enrolled in clinical trials. For the rapid infusion protocol, 20% of the dose was administered over 30 minutes and the remaining 80% over 60 minutes. RESULTS: From April 1 to May 31, 2019, 25 patients received 53 90-minute infusions of daratumumab. Premedication included corticosteroids, antipyretics, antihistamines, and if necessary a leukotriene receptor antagonist. No grade 3 or grade 4 IRRs were observed. CONCLUSION: From the third infusion, we found that a rapid administration of daratumumab (90 vs 210 minutes) was well tolerated and safe. It would be interesting to test this regimen from the second infusion.

Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).

Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma.

It is important to have an effective therapy for patients with multiple myeloma (MM) at first relapse, particularly if an autologous stem cell transplant (ASCT) is considered at this stage. This multicenter, phase 2 trial evaluated the efficacy and safety of weekly oral pomalidomide-cyclophosphamide-dexamethasone (PCD) in patients with MM in first relapse after treatment with lenalidomide-bortezomib-dexamethasone (RVD). All patients had received RVD as induction and consolidation therapy, plus lenalidomide maintenance for 1 year (arm A). Half had also received an ASCT after induction (arm B). At MM relapse, all patients received 4 oral cycles of pomalidomide 4 mg (days 1-21), cyclophosphamide 300 mg (days 1, 8, 15, and 22), and dexamethasone 40 mg (days 1-4 and days 15-18 of a 28-day cycle; PCD). Responding patients in arm A underwent ASCT and received 2 additional cycles of PCD, whereas those in arm B received 5 cycles of PCD. All patients received pomalidomide-dexamethasone maintenance until disease progression. Primary end point was partial remission or better after the initial 4 cycles of PCD. Responses were obtained in 82/97 (85%) patients evaluated: complete remission (n = 1; 1%), very good partial remission (n = 32; 33%), and partial remission (n = 49; 51%). Three patients (3%) had stable disease, and 6 (6%) had disease progression (6 response failures). Forty-five (94%) of the 48 patients in arm A underwent planned ASCT. PCD was effective therapy after first relapse with RVD. After 4 cycles, the rate of partial remission or better was 85%, and 94% of planned ASCTs were performed. Toxicity was mostly hematologic and manageable. This trial was registered at www.clinicaltrials.gov as #NCT02244125.

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma.

OBJECTIVES: To investigate the efficacy, safety, and cost of a pomalidomide-dexamethasone regimen in patients with relapsed and refractory multiple myeloma (RRMM). METHODS: All patients (n = 63) treated with pomalidomide-dexamethasone for RRMM in our university hospital between August 2013 and October 2015 were included. RESULTS: Pomalidomide was discontinued early due to progression (before the 4th cycle) in 17 (27%) patients. No case was discontinued for intolerance. The only independent factor that predicted early pomalidomide discontinuation was time from diagnosis to pomalidomide initiation <3 years. Overall response rate was 51% including complete response in 8%, very good partial response in 25%, and partial response in 19% patients. Thirteen (33%) patients showed stable disease. Median overall survival was 6.4 months in the 17 patients who discontinued pomalidomide early vs 26.8 months in the 14 patients with stable disease vs not achieved in the 32 responders (log-rank; P < 10-3 ). The most common grade ≥3 adverse events were neutropenia (14%) and infections (25%). The incremental cost-effectiveness ratio of pomalidomide-dexamethasone compared with dexamethasone alone was estimated at €39 911 per life-year gained. CONCLUSIONS: The study demonstrated that pomalidomide-dexamethasone regimen has a long-term favorable safety-efficacy profile in RRMM patients. The survival benefit is substantial even in patients with stable disease.

Evolution of procalcitonin, C-reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis.

Unlike bacterial infections, the value of procalcitonin (PCT) in detecting fungal infections in leukaemia patients is not clear. To determine whether the monitoring of PCT coupled with C-reactive protein (CRP) and fibrinogen (Fib) could be helpful in the management of pulmonary aspergillosis (IPA) or mucormycosis (PM), we retrospectively analysed the evolution of PCT, CRP and Fib levels in 94 leukaemia patients with proven/probable IPA (n = 77) or PM (n = 17) from D-12 to D12 relative to IFI onset defined as D0. Overall, 2140 assays were performed. From D-12 to D0, 12%, 5% and 1.4% of patients had PCT >0.5, 1 and 1.5 µg l(-1) , respectively, while CRP was >50, 75 and 100 mg l(-1) in 84%, 70% and 57% and Fib was >4, 5 and 6 g l(-1) in 96%, 80% and 61% of cases respectively (P < 10(-7) ). The same trends were observed from D1 to D12. Overall, between D-12 and D12, only 6.4% of patients had PCT >1.5 µg l(-1) , while CRP >100 mg l(-1) and Fib >6 g l(-1) were observed in 80% and 75% of cases respectively (P < 10(-7) ). In leukaemia patients, IPA or PM was accompanied by a significant increase in CRP and Fib while PCT remained low.

Is It Time to Include CT "Reverse Halo Sign" and qPCR Targeting Mucorales in Serum to EORTC-MSG Criteria for the Diagnosis of Pulmonary Mucormycosis in Leukemia Patients?

In 23 leukemia patients with proven (n = 17) or possible (n = 6) pulmonary mucormycosis (PM), the presence of reversed halo sign on computed tomography was strongly associated with the positivity of quantitative polymerase chain reaction assays targeting Mucorales in the serum, confirming the value of these two tools for the diagnosis of PM in this setting.

[Evaluation of the new Hevylite™ IgA assay for the diagnosis and follow-up of monoclonal gammopathies]. / Évaluation du nouveau test Hevylite™ IgA dans le diagnostic et le suivi des gammapathies monoclonales.

Multiple myeloma diagnosis and follow-up are based on monoclonal protein measurement. The estimation of monoclonal immunoglobulin production requires serum protein electrophoresis, immunoelectrophoresis and free light chain assay. However these classical assays have some limitations. Hevylite™ IgA (Binding Site) is a new nephelometric/turbidimetric assay allowing the IgA κ and IgA λ measurement. The aim of this study was to determine the performance of this assay, for the diagnosis and follow-up of myeloma patients at different stages. Sixty seven frozen sera from 26 patients were assayed. Total IgA, IgA κ, IgA λ concentrations, serum protein electrophoresis and serum immunofixation were performed at diagnosis and during follow-up. All myeloma patients had an abnormal IgA κ/IgA λ ratio at diagnosis. During disease monitoring, the IgA κ or IgA λ concentrations correlated well with the electrophoretic estimation of the monoclonal spike and the values of total IgA. Hevylite™ test was more sensitive than serum protein electrophoresis and provided numerical and reproductible assessment of the monoclonal and non-monoclonal isotype. The IgA κ/IgA λ ratio allowed early prediction of disease relapse. Hevylite™ is an interesting assay especially when the monoclonal IgA comigrates on electrophoresis with normal proteins making impossible a reliable densitometric estimation. Hevylite™ might become an important assay in the biological exploration of gammopathies.

Autologous stem cell transplantation: an effective salvage therapy in multiple myeloma.

Eighty-one patients treated with high-dose therapy and autologous stem cell transplantation (ASCT) as part of salvage therapy after a frontline ASCT were included in a retrospective analysis. The median time between the first and the salvage ASCT was 47 months. After salvage ASCT, 75 patients (93%) achieved at least a partial response, including 67% very good partial responses, and no toxic death was reported. Sixteen patients (20%) underwent consolidation therapy, whereas 30 patients (37%) underwent some form of maintenance therapy after salvage ASCT. For all patients, the median overall survival (OS) was 10 years from diagnosis and 4 years from salvage ASCT. The median progression-free survival (PFS) from the date of the first ASCT to the date of the first relapse was 40 months, and the median PFS from the date of salvage ASCT to the date of subsequent progression was 18 months. In the multivariate analysis of prognostic factors, three independent factors unfavorably affected PFS: a short duration of response to the first ASCT (cut-off value of 24 months), a response less than a very good partial response after salvage therapy, and no maintenance treatment after salvage ASCT. Age over 60 years and a short duration of response after the first ASCT were the two factors adversely affecting OS from the time of diagnosis and OS from the time of salvage ASCT. Our data show that salvage ASCT is a feasible option that should be routinely considered at the time of relapse for patients with a response duration of more than 2 years to frontline high-dose therapy.

Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

PURPOSE: This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m(2) intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months). RESULTS: Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P 0.001), and the median duration of response was longer (17.9 v 13.4 months; P.04) [corrected].The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia. CONCLUSION: VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.

Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial.

Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With a median follow-up of 23 months, overall survival was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and janus kinase 2 (JAK2) genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1γ, did not predict response or survival on DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in approximately 40% of CMML patients with advanced myeloproliferative or myelodysplastic features and suggested that CJUN and CMYB expression could be potential biomarkers in this setting. This trial is registered at EudraCT (eudract.ema.europa.eu) as #2008-000470-21 and www.clinicaltrials.gov as #NCT01098084.

Airborne Aspergillus contamination during hospital construction works: efficacy of protective measures.

BACKGROUND: The Dijon University Hospital in Dijon, France is involved in a large construction program with heavy truck traffic and a very dusty environment. This study aimed to assess the impact of outdoor hospital construction work on Aspergillus air contamination in the immediate environment of patients at high risk for aspergillosis in the presence of protective measures. METHODS: Prospective air and surface sampling (n=1301) was performed in 3 hospital units over a 30-month period. Generalized estimating equations were used to test the relationship between Aspergillus air contamination and the different variables (construction period, air treatment system, and surface contamination). RESULTS: Positivity rates of Aspergillus spp varied from 21.1% before construction work to 16.9% during work for air samples (P=.07), and the associated mean fungal load varied from 1.21 colony-forming units (CFU)/m(3) to 0.64 CFU/m(3) (P=.04). In multivariate analysis, only the use of an air treatment system was associated with decreased airborne Aspergillus contamination (P < .0001). No significant difference was observed between the presence or absence of construction work and the proportion of airborne Aspergillus contamination (P=.91) or the Aspergillus fungal load (P=.10). CONCLUSIONS: No influence of hospital construction work on airborne Aspergillus contamination was demonstrated when protective measures were taken, including reinforcement of the importance of environmental cleaning.

Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial.

PURPOSE: Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. PATIENTS AND METHODS: Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. RESULTS: After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). CONCLUSION: This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.