Publications by authors named "Michel Delforge"

122 Publications

Immunomodulators in newly diagnosed multiple myeloma: current and future concepts.

Expert Rev Hematol 2021 Mar 31:1-12. Epub 2021 Mar 31.

Department of Hematology, University of Leuven and Leuven Cancer Institute, Leuven, Belgium.

: Impressive therapeutic progress is being made in the management of multiple myeloma (MM). his progress is related to the introduction of several new classes of therapeutic agents including proteasome inhibitors, immunomodulatory drugs (IMiDs) and monoclonal antibodies (MoAbs).: In this manuscript, the role of the IMiDs thalidomide and lenalidomide in the management of newly diagnosed MM is discussed. The mode of action of IMiDs and their role in the management of newly diagnosed MM patients is highlighted. In addition, clinical data on how MoAbs such as the anti-CD38 antibody daratumumab can further increase the efficacy of IMiD-based first-line anti-myeloma regimens are provided. A database search in PubMed was carried out.: Immunomodulation has become an indispensable part of successful anti-myeloma regimens both at relapse and at diagnosis. The combination of lenalidomide plus dexamethasone with an anti-CD38 MoAb such as daratumumab and a proteasome inhibitor such as bortezomib is currently one of the most potent first-line treatment regimens for MM. A better understanding on how IMiDs synergize with existing and new anti-myeloma treatments can further improve the outcome for patients. Optimal first-line therapy will continue to benefit the long-term outcome of a growing population of young and elderly MM patients.
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http://dx.doi.org/10.1080/17474086.2021.1905513DOI Listing
March 2021

Identifying frailty in clinically fit patients diagnosed with hematological malignancies using a simple clinico-biological screening tool: The HEMA-4 study.

J Geriatr Oncol 2021 Feb 26. Epub 2021 Feb 26.

Department of Hematology, Institut Jules Bordet, ULB, Brussels, Belgium.

Introduction: This study aims to develop and validate a simple score to estimate survival in the older population suffering from malignant hemopathies.

Methods: We prospectively recruited 285 patients, aged ≥65 years, admitted to receive chemotherapy. At inclusion, a geriatric assessment was performed. Cox proportional hazards models were performed to assess correlations between vulnerabilities and one-year survival. We developed a frailty score, HEMA-4, based on the most powerful prognostic factors. It was externally confirmed with an independent cohort.

Results: In the development cohort, 206 patients were evaluable. Mean age was 76 years (range 65-90). The HEMA-4 score was created based on four independent predictive factors for survival: cognitive impairment (MMSE<27), comorbidities (≥2 on Charlson comorbidity index), CRP (≥10 mg/L) and low albumin level (<35 g/L). The population was stratified into three groups: good prognosis (score = 0-1, n = 141), intermediate prognosis (score = 2, n = 37) and poor prognosis (score = 3-4, n = 28). Their respective one-year survival was 74%, 51% (HR = 2.30; 95% CI =1.31-4.05; p < 0.01) and 36% (HR = 3.95; 95% CI =2.23-6.98; p < 0.01). In the validation cohort (n = 25), the one-year survival was 78% in the good prognosis group (n = 9) and 50% in the intermediate prognosis group (n = 6). The poor prognosis group had a median survival of four months in the development cohort and six months in the validation cohort (n = 10).

Conclusion: The HEMA-4 score is a simple score that combines cognitive impairment, comorbidities, inflammation and low albumin level. Our data suggest that it predicts survival among older patients suffering from malignant hemopathies referred to receive chemotherapy regardless of their chronological age.
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http://dx.doi.org/10.1016/j.jgo.2021.02.019DOI Listing
February 2021

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.

N Engl J Med 2021 02;384(8):705-716

From the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute (N.C.M.), the Veterans Affairs Boston Healthcare System, Harvard Medical School (N.C.M.), and Massachusetts General Hospital (N.R.), Boston, and bluebird bio, Cambridge (F.P., M.M.) - all in Massachusetts; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas (L.D.A.); the University of California, San Francisco, San Francisco (N.S.); Icahn School of Medicine at Mount Sinai, New York (D.M.); Sarah Cannon Research Institute and Tennessee Oncology, Nashville (J.B.); Emory School of Medicine, Atlanta (S.L.); Mayo Clinic, Rochester, MN (Y.L.); Hackensack University Medical Center, Hackensack (D.S.), and Bristol-Myers Squibb, Princeton (J.N.C., S.K., P.P., L.H., T.B.C., K.H.) - both in New Jersey; Institut Josep Carreras and Institut Catala d'Oncologia, Hospital Germans Trias i Pujol, Badalona (A.O.), and Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Cáncer, Pamplona (J.S.-M.) - both in Spain; Centre Hospitalier Universitaire (CHU) de Nantes, Nantes (P.M.), and CHU de Lille, University of Lille, INSERM Unité 1286, Institute for Translational Research in Inflammation, Lille (I.Y.-A.) - both in France; University Hospital Leuven, Leuven, Belgium (M.D.); "Seràgnoli" Institute of Hematology, Bologna University School of Medicine, Bologna (M.C.), the Department of Oncology and Hematology, University of Milan, Milan (A.R.), and Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (A.R.) - all in Italy; University Hospital of Würzburg, Würzburg (H.E.), University Hospital Heidelberg (H.G.) and the National Center for Tumor Diseases (H.G.), Heidelberg, the University Medical Center Hamburg-Eppendorf, Hamburg (K.W.), and Universitätsklinikum Tübingen, Tübingen (K.W.) - all in Germany; and Princess Margaret Cancer Centre, Toronto (D.R.).

Background: Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma.

Methods: In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma. Patients with disease after at least three previous regimens including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody were enrolled. Patients received ide-cel target doses of 150 × 10 to 450 × 10 CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses).

Results: Of 140 patients enrolled, 128 received ide-cel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD)-negative status (<10 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion.

Conclusions: Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome. (Funded by bluebird bio and Celgene, a Bristol-Myers Squibb company; KarMMa ClinicalTrials.gov number, NCT03361748.).
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http://dx.doi.org/10.1056/NEJMoa2024850DOI Listing
February 2021

A double-edged sword.

Breathe (Sheff) 2020 Sep;16(3):200017

Dept of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium.

https://bit.ly/2SDKwE5.
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http://dx.doi.org/10.1183/20734735.0017-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792833PMC
September 2020

Recommendations on the management of multiple myeloma in 2020.

Acta Clin Belg 2020 Dec 23:1-17. Epub 2020 Dec 23.

Institut Jules Bordet, ULB, Brussels, Belgium.

With the introduction of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, major improvements have been achieved in the treatment of multiple myeloma (MM), with a significant impact on the outcome of this disease. Different treatment combinations are now in use and other therapies are being developed. Based on an extensive review of the recent literature, we propose practical recommendations on myeloma management, to be used by hematologists as a reference for daily practice.
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http://dx.doi.org/10.1080/17843286.2020.1860411DOI Listing
December 2020

Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial.

J Clin Oncol 2021 Jan 16;39(3):227-237. Epub 2020 Dec 16.

Department of Oncology, Hematology, BMT with Department of Pneumology, University Medical Center Hamburg, Hamburg, Germany.

Purpose: To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study.

Patients And Methods: PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs.

Results: A total of 737 transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma were randomly assigned to D-Rd (n = 368) or Rd (n = 369). Compliance with PRO assessments was high at baseline (> 90%) through month 12 (> 78%) for both groups. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item global health status scores improved from baseline in both groups and were consistently greater with D-Rd at all time points. A global health status benefit was achieved with D-Rd, regardless of age (< 75 and ≥ 75 years), baseline Eastern Cooperative Oncology Group (ECOG) performance status score, or depth of response. D-Rd treatment resulted in significantly greater reduction in pain scores as early as cycle 3 ( = .0007 Rd); the magnitude of change was sustained through cycle 12. Reductions in pain with D-Rd were clinically meaningful in patients regardless of age, ECOG status, or depth of response. Similarly, PRO improvements were observed with D-Rd and Rd on the EuroQol 5-dimensional descriptive system visual analog scale score.

Conclusion: D-Rd compared with Rd was associated with faster and sustained clinically meaningful improvements in PROs, including pain, in transplant-ineligible patients with newly diagnosed multiple myeloma regardless of age, baseline ECOG status, or depth of treatment response.
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http://dx.doi.org/10.1200/JCO.20.01370DOI Listing
January 2021

Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR.

Leukemia 2020 Oct 16. Epub 2020 Oct 16.

Hematology Department, University Hospital Hôtel-Dieu, Nantes, France.

To understand the profile of best responders (complete response or better [≥CR]) to carfilzomib, we described the characteristics, progression-free survival (PFS), overall survival (OS) data, and the safety of patients who achieved ≥CR to carfilzomib-based treatment in ASPIRE and ENDEAVOR. In post hoc analyses from ASPIRE and ENDEAVOR, median PFS and OS were longer for ≥CR patients versus those who achieved a very good partial response or partial response (VGPR/PR). In the carfilzomib arm of ASPIRE, median PFS was 50.4 months for ≥CR versus 22.1 months for VGPR/PR; median OS was 67.0 versus 44.2 months, respectively. In the carfilzomib arm of ENDEAVOR, median PFS was 34.0 for ≥CR versus 20.4 months for VGPR/PR; median OS was non-estimable. Despite the longer treatment duration, fewer patients with ≥CR versus VGPR/PR experienced treatment-emergent adverse events that led to discontinuation of carfilzomib-based treatment in ASPIRE or ENDEAVOR. Low serum lactate dehydrogenase was the only factor associated with achieving ≥CR vs patients not achieving CR in ASPIRE in multivariate regression analyses. No association was found between cytogenetic risk status and reaching ≥CR. Carfilzomib treatment may lead to rapid and deep responses, irrespective of most patient characteristics.
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http://dx.doi.org/10.1038/s41375-020-01049-5DOI Listing
October 2020

Determination of free light chains: assay-dependent differences in interpretation.

Clin Chem Lab Med 2020 Sep 2;59(2):e69-e71. Epub 2020 Sep 2.

Hematology, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1515/cclm-2020-0938DOI Listing
September 2020

Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network.

Leukemia 2021 01 19;35(1):31-44. Epub 2020 Aug 19.

Erasmus MC Cancer Institute, Erasmus University of Rotterdam, Rotterdam, The Netherlands.

Vaccination is one of the most successful medical interventions that has saved the life of millions of people. Vaccination is particularly important in patients with multiple myeloma, who have an increased risk of infections due to the disease-inherent immune suppression, and because of the immune suppressive effects of therapy. Hence, all appropriate measures should be exploited, to elicit an effective immune response to common pathogens like influenza, pneumococci, varicella zoster virus, and to those bacteria and viruses (haemophilus influenzae, meningococci, and hepatitis) that frequently may pose a significant risk to patients with multiple myeloma. Patients after autologous, and specifically after allogeneic transplantation have severely reduced antibody titers, and therefore require a broader spectrum of vaccinations. Response to vaccination in myeloma often is less vigorous than in the general population, mandating either measurement of the postvaccination antibody titers and/or repeating the vaccination. Here, we compile the existing data on vaccination in multiple myeloma and provide recommendations for clinical practice.
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http://dx.doi.org/10.1038/s41375-020-01016-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787974PMC
January 2021

Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT.

Bone Marrow Transplant 2021 Jan 24;56(1):210-217. Epub 2020 Jul 24.

University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n = 446), auto-auto (n = 105), or auto-allo (n = 72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45-58%) for single auto, 60% (95% CI, 49-72%) for auto-auto, and 67% (95% CI, 53-80%) for auto-allo (p = 0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12-22%), 33% (95% CI, 22-43%), and 34% (95% CI, 21-38%; p = 0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p = 0.007) and auto-allo (HR, 0.45; p = 0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p = 0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p = 0.097). No significant difference in OS was identified between the groups in patients with del(17p).
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http://dx.doi.org/10.1038/s41409-020-01007-wDOI Listing
January 2021

Novel risk stratification algorithm for estimating the risk of death in patients with relapsed multiple myeloma: external validation in a retrospective chart review.

BMJ Open 2020 07 14;10(7):e034209. Epub 2020 Jul 14.

Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland, UK.

Objectives And Design: A novel risk stratification algorithm estimating risk of death in patients with relapsed multiple myeloma starting second-line treatment was recently developed using multivariable Cox regression of data from a Czech registry. It uses 16 parameters routinely collected in medical practice to stratify patients into four distinct risk groups in terms of survival expectation. To provide insight into generalisability of the risk stratification algorithm, the study aimed to validate the risk stratification algorithm using real-world data from specifically designed retrospective chart audits from three European countries.

Participants And Setting: Physicians collected data from 998 patients (France, 386; Germany, 344; UK, 268) and applied the risk stratification algorithm.

Methods: The performance of the Cox regression model for predicting risk of death was assessed by Nagelkerke's R, goodness of fit and the C-index. The risk stratification algorithm's ability to discriminate overall survival across four risk groups was evaluated using Kaplan-Meier curves and HRs.

Results: Consistent with the Czech registry, the stratification performance of the risk stratification algorithm demonstrated clear differentiation in risk of death between the four groups. As risk groups increased, risk of death doubled. The C-index was 0.715 (95% CI 0.690 to 0.734).

Conclusions: Validation of the novel risk stratification algorithm in an independent 'real-world' dataset demonstrated that it stratifies patients in four subgroups according to survival expectation.
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http://dx.doi.org/10.1136/bmjopen-2019-034209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365483PMC
July 2020

Comparison of 2 Serum-Free Light-Chain Assays in CKD Patients.

Kidney Int Rep 2020 May 30;5(5):627-631. Epub 2020 Jan 30.

Department of Microbiology and Immunology, Laboratory of Molecular Immunology (Rega Institute), KU Leuven, Leuven, Belgium.

Introduction: Quantification of serum-free light chains (FLCs) is important in the diagnosis and monitoring of paraprotein-related diseases. There are currently 2 FLC assays available: the Freelite assay (Binding Site) and the N Latex assay (Siemens). There is emerging evidence that these assays give different results, but it is not established how kidney dysfunction affects these assays differently.

Methods: In this study, we measured and compared serum FLCs in patients with mild-to-moderate chronic kidney disease (CKD) using both assays.

Results: Although κ FLCs are higher by Freelite, λ FLCs are higher by N Latex. Both κ and λ FLCs correlate inversely with estimated glomerular filtration rate (eGFR) in the 2 assays, but this effect is more pronounced in λ-free light-chain measurement by N Latex. Consequently, although the κ/λ ratio by Freelite is inversely correlated by eGFR, the κ/λ ratio by N Latex is positively correlated with eGFR.

Conclusion: Our results clearly demonstrate that the 2 available FLC assays cannot be used interchangeably in patients with CKD.
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http://dx.doi.org/10.1016/j.ekir.2020.01.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210599PMC
May 2020

Different MAF translocations confer similar prognosis in newly diagnosed multiple myeloma patients.

Leuk Lymphoma 2020 08 19;61(8):1885-1893. Epub 2020 Apr 19.

John Theurer Cancer Center, Hackensack UMC, Hackensack, NJ, USA.

The MAF translocations, t(14;16) and t(14;20), are considered as adverse prognostic factors based on few studies with small sample sizes. We report on their prognostic impact in a large group of 254 patients - 223 (87.8%) with t(14;16) and 31 (12.2%) with t(14;20). There were no intergroup differences in survival estimates. Median progression-free survival was 16.6 months for t(14;16) and 24.9 months for t(14;20) ( = 0.28). Median overall survival (OS) was 54.0 months and 49.0 months, respectively ( = 0.62). Median OS in patients who underwent double autologous stem cell transplantation (ASCT) was 107.0 months versus 60.0 months in patients who received single ASCT ( < 0.001). ISS 3 was associated with shorter OS (HR = 1.89; 95% CI 1.24-3.19;  = 0.005) in Cox analysis. Our study suggests that t(14;20) should be considered as an adverse factor of equal prognostic implication to t(14;16).
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http://dx.doi.org/10.1080/10428194.2020.1749605DOI Listing
August 2020

Ultra-low depth sequencing of plasma cell DNA for the detection of copy number aberrations in multiple myeloma.

Genes Chromosomes Cancer 2020 08 5;59(8):465-471. Epub 2020 May 5.

Center for Human Genetics, KU Leuven, Leuven, Belgium.

Cytogenetic abnormalities are powerful prognostic factors in multiple myeloma (MM) and are routinely analyzed by FISH on bone marrow (BM) plasma cells (PC). Although considered the gold standard, FISH experiments can be laborious and expensive. Therefore, array-CGH (aCGH) has been introduced as an alternative approach for detecting copy number aberrations (CNA), reducing the number of FISH experiments per case and yielding genome-wide information. Currently, next generation sequencing (NGS) technologies offer new perspectives for the diagnostic workup of malignant disorders. In this study, we examined ultra-low depth whole genome sequencing (LDS) as a valid alternative for aCGH for the detection of CNA in BM PC in MM. To this end, BM aspirates obtained in a diagnostic setting from 20 MM cases were analyzed. CD138+ cell-sorted samples were subjected to FISH analysis. DNA was extracted for subsequent aCGH and LDS analysis. CNA were detected by aCGH and LDS in all but one case. Importantly, all CNA identified by parallel first generation aCGH analysis were also detected by LDS, along with six additional CNA in five cases. One of these additional aberrations was in a region of prognostic importance in MM and was confirmed using FISH. However, risk stratification in these particular cases was unaffected. Thus, a perfectly concordant prognostication between array-CGH and LDS was observed. This validates LDS as a novel and cost-efficient tool for the detection of CNA in MM.
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http://dx.doi.org/10.1002/gcc.22848DOI Listing
August 2020

A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma.

Am J Hematol 2020 05 29;95(5):503-509. Epub 2020 Feb 29.

John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey.

The t(14;16) translocation, found in 3%-5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real-world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7-18.7), the median progression-free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5-2.4) and 4.1 years (95% CI 3.3-5.5), respectively. Worse OS was predicted by age > 60 years (HR = 1.65, 95% CI [1.05-2.58]), as well as revised International Scoring System (R-ISS) 3 (vs R-ISS 2; HR = 2.59, 95% CI [1.59-4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R-ISS 3 predict poor survival.
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http://dx.doi.org/10.1002/ajh.25758DOI Listing
May 2020

Insights on Multiple Myeloma Treatment Strategies.

Hemasphere 2019 Feb 27;3(1):e163. Epub 2018 Dec 27.

Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future.
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http://dx.doi.org/10.1097/HS9.0000000000000163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745941PMC
February 2019

Carfilzomib-induced reticulocytosis in patients with multiple myeloma is caused by impaired terminal erythroid maturation.

Leukemia 2020 02 29;34(2):651-655. Epub 2019 Aug 29.

Department of Internal Medicine-Hematology, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1038/s41375-019-0565-yDOI Listing
February 2020

Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network.

Haematologica 2019 12 22;104(12):2358-2360. Epub 2019 Aug 22.

University of Wurzburg, Wurzburg, Germany.

Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strategy has been approved in relapsed/refractory MM, it will become one of the most important indications for this therapy in Europe and world-wide. This manuscript proposes practical considerations for the use of CAR-T cell therapy in MM, and discusses several important issues for its future development.
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http://dx.doi.org/10.3324/haematol.2019.224204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959167PMC
December 2019

Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma.

N Engl J Med 2019 08;381(8):727-738

From the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (A.C., S.P., S.J.), and New York University Langone Medical Center (D.K.) - both in New York; the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia (D.T.V.); the School of Medicine, National and Kapodistrian University of Athens, Athens (M.G., M. Dimopoulos); the Winship Cancer Institute, Emory University, Atlanta (A.K.N., S.L.); Massachusetts General Hospital Cancer Center (A.J.Y.), Tufts Medical Center (R.L.C.), and the Dana-Farber Cancer Institute (P.G.R.), Boston, and Karyopharm Therapeutics, Newton (M.G.K., S.S., L.L., S. Tang, C.P., J.-R.S.-M., M.C., H.C., Y.L., J.S.) - all in Massachusetts; Johns Hopkins University, Baltimore (C.A.H.); the University of Nantes, Nantes (P.M.), Hôpital Necker (L.F.), Hôpital Saint-Antoine (M.M.), and La Pitié-Salpêtrière Hospital (S.C.), Paris, University Hospital, Lille (T.F.), Centre Hospitalier Lyon Sud, Pierre-Benite (L.K.), and Centre Hospitalo-Universitaire Vandoeuvre-lès-Nancy, Nancy (A.P.) - all in France; the Mayo Clinic, Rochester, MN (D.D.); the University of Michigan, Ann Arbor (C.C.); the Mayo Clinic of Arizona, Phoenix (A.K.S.); Hackensack University Medical Center, Hackensack, NJ (J.R.); Washington University School of Medicine, St. Louis (R.V.); Lineberger Comprehensive Cancer Center at University of North Carolina-Chapel Hill, Chapel Hill (S. Tuchman); the University of Heidelberg, Heidelberg (M.S.R.), University Medical Center Hamburg-Eppendorf, Hamburg (K.C.W.), the University of Tübingen, Tübingen (K.C.W.), University Hospital Würzburg, Würzburg (M.S.), the University of Freiburg, Freiburg (M.E.), and Gemeinschaftspraxis Hämatologie-Onkologie, Dresden (T.I.) - all in Germany; the University of Leuven, Leuven (M. Delforge), Institut Jules Bordet, Université Libre de Bruxelles, Brussels (N.M.), University Hospital Ghent, Ghent (P.V.), and Centre Hospitalier Universitaire Université Catholique de Louvain Namur, Yvoir (C.D.) - all in Belgium; Vanderbilt University Medical Center, Nashville (R.F.C.); Sylvester Cancer Center, University of Miami, Miami (J.E.H.); the University of Alabama at Birmingham, Birmingham (L.J.C.); Yale School of Medicine, New Haven, CT (T.L.P.); Baylor University Medical Center, Dallas (M.L.); the David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (G.S.); and University Hospital Krems, Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria (K.P.).

Background: Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options.

Methods: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point.

Results: A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients.

Conclusions: Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).
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http://dx.doi.org/10.1056/NEJMoa1903455DOI Listing
August 2019

Comparison of IVIg 5% Versus 10% in hematological patients with a secondary immunodeficiency disorder.

Acta Clin Belg 2021 Feb 17;76(1):49-52. Epub 2019 Aug 17.

Department of Hematology, University Hospital Leuven , Leuven, Belgium.

: The aim of this study was to evaluate the administration of intravenous immunoglobulin (IVIg) solutions (5% vs. 10%) in hematological patients suffering from a secondary immunodeficiency (SID) to optimize infusion duration and hospitalization time. : A monocentric, observational study in 30 patients with secondary hypogammaglobulinemia due to a lymphoproliferative disorder currently under IVIg 5% treatment. A sequential approach was followed with observations during IVIg 5% and 10% administration 3 to 4 weeks later. Infusion time, time spent at the day clinic, IVIg-related adverse events and number of actions taken by the nursing staff were evaluated and compared between the 5% and 10% infusions. Questionnaires for patients and nursing staff were obtained after IVIg 10% to assess their satisfaction with the change of infusion. : Average infusion time was reduced from 4.92 h to 2.29 h (p < 0.0001). Time spent at the day clinic was 5.87 h for the 5% IVIg administration and 4.56 h for the 10% (p = 0.0005). IVIg-related adverse events rose from 0 to 0.43 per patient. No serious adverse events were reported. Nursing actions per patient decreased from 1.03 to 0.67. Patient and nursing satisfaction were respectively 83% and 96% in favor of IVIg 10%. : A 10% IVIg solution can significantly reduce infusion time and overall duration of the day clinic visit. Care must be taken to minimize new infusion-related adverse events. Switching to a 10% IVIg administration increases patient and nursing satisfaction but also requires additional workflow changes to further shorten the day clinic visit.
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http://dx.doi.org/10.1080/17843286.2019.1655860DOI Listing
February 2021

Development and validation of a novel risk stratification algorithm for relapsed multiple myeloma.

Br J Haematol 2019 11 6;187(4):447-458. Epub 2019 Aug 6.

Pharmerit International, Rotterdam, the Netherlands.

Multiple myeloma (MM) is a malignancy with varying survival outcomes and drivers of disease progression. Existing MM staging tools were developed using data from newly diagnosed patients. As patient characteristics and disease-related factors change between diagnosis and the initiation of second-line (2L) treatment, an unmet need exists for a tool that can evaluate risk of death at first relapse. We have developed a risk stratification algorithm (RSA) using data from patients with MM who were at 2L. Hazard ratios for independent predictors of overall survival (OS) were derived from a Cox models, and individual patient scores were calculated for total risk. K-adaptive partitioning for survival was used to stratify patients into groups based on their scores. Relative risk doubled with ascending risk group; median OSs for patients in group 1 (lowest risk)-4 (highest risk) were 61·6, 29·6, 14·2 and 5·9 months, respectively. Differences in OS between risk groups were significant. Similar stratification was observed when the RSA was applied to an external validation data set. In conclusion, we have developed a validated RSA that can quantify total risk, frailty risk and disease aggressiveness risk, and stratify patients with MM at 2L into groups with profoundly different survival expectations.
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http://dx.doi.org/10.1111/bjh.16105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899684PMC
November 2019

Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study.

Lancet 2019 07 3;394(10192):29-38. Epub 2019 Jun 3.

Erasmus University Medical Center Cancer Institute, Rotterdam, Netherlands.

Background: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma.

Methods: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383.

Findings: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21-2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10 sensitivity threshold, assessed by multiparametric flow cytometry; both p<0·0001). Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0·47, 95% CI 0·33-0·67, p<0·0001). 46 deaths on study were observed (14 vs 32, 0·43, 95% CI 0·23-0·80). The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%).

Interpretation: D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma.

Funding: The Intergroupe Francophone du Myélome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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http://dx.doi.org/10.1016/S0140-6736(19)31240-1DOI Listing
July 2019

Velocities of Naturally Occurring Myocardial Shear Waves Increase With Age and in Cardiac Amyloidosis.

JACC Cardiovasc Imaging 2019 12 13;12(12):2389-2398. Epub 2019 Feb 13.

Department of Cardiovascular Science, Division of Cardiology, University Hospital Leuven, University of Leuven, Leuven, Belgium. Electronic address:

Objectives: This study sought to evaluate whether velocity of naturally occurring myocardial shear waves (SW) could relate to myocardial stiffness (MS) in vivo.

Background: Cardiac SW imaging has been proposed as a noninvasive tool to assess MS. SWs occur after mechanical excitation of the myocardium (e.g., mitral valve closure [MVC] and aortic valve closure [AVC]), and their propagation velocity is theoretically related to MS, thus providing an opportunity to assess stiffness at end-diastole (ED) and end-systole. However, given that SW propagation in vivo is complex, it remains unclear whether natural SW velocity effectively relates to MS.

Methods: This study prospectively enrolled 50 healthy volunteers (HV) (43.7 ± 17.1 years of age) and 18 patients with cardiac amyloidosis (CA) (68.0 ± 9.8 years of age). HV were divided into 3 age groups: group I, 20 to 39 years of age (n = 24); group II, 40 to 59 years of age (n = 11); and group III, 60 to 80 years of age (n = 15). Parasternal long-axis views were acquired using an experimental scanner. Tissue (Doppler) acceleration maps were extracted from an anatomical M-mode along the midline of the left ventricular septum.

Results: SW propagation velocity was significantly higher in CA patients than in HV after both MVC (3.54 ± 0.93 m/s vs. 6.33 ± 1.63 m/s, respectively; p < 0.001) and AVC (3.75 ± 0.76 m/s vs. 5.63 ± 1.13 m/s, respectively; p < 0.001). Similarly, SW propagation velocity differed significantly among age groups in HV, with a significantly higher value for group III than for group I, both occurring after MVC (p < 0.001) and AVC (p < 0.01). Moreover, SW propagation velocity after MVC was found to be significantly higher in patients with an increasing grade of diastolic dysfunction (p < 0.001). Finally, positive correlation was found between SW velocities after MVC and mitral inflow-to-mitral relaxation velocity ratio (E/E') (r = 0.74; p = 0.002).

Conclusions: End-diastole SW velocities were significantly higher in patients with CA, patients with a higher grade of diastolic dysfunction, and elderly volunteers. These findings thus suggest that the speed of naturally induced SWs may be related to MS.
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http://dx.doi.org/10.1016/j.jcmg.2018.11.029DOI Listing
December 2019

Bortezomib retreatment for relapsed and refractory multiple myeloma in real-world clinical practice.

Health Sci Rep 2019 Jan 7;2(1):e104. Epub 2018 Dec 7.

Department of Hematology University Hospital Leuven Leuven Belgium.

Aims: Studies have shown that bortezomib retreatment is effective in relapsed/refractory multiple myeloma (MM). The observational, prospective electronic VELCADE OBservational Study (eVOBS) study assessed bortezomib-based therapies for patients with MM in everyday practice. Here, we report on those patients receiving retreatment with bortezomib.

Methods: Consenting adults scheduled to receive bortezomib for MM were enrolled at 162 sites across Europe, Canada, Brazil, Russia, and Turkey between 2006 and 2010. Retrospective data on prior therapies and prospective observational data after bortezomib initiation were captured electronically at baseline, after every bortezomib cycle, and every 12 weeks after discontinuation or progression. Investigator-assessed responses and adverse events (AEs) were evaluated.

Results: Ninety-six of 873 patients enrolled to eVOBS received bortezomib as first retreatment for progressive disease during the prospective observation period. Median age was 62 years, 53% were male, and median number of prior therapies at retreatment was 4. Overall, 41% of patients initiated bortezomib retreatment in combination with dexamethasone, 16% in combination with lenalidomide, and 21% received monotherapy. Rate of partial response or better (≥PR) was 75% at initial bortezomib therapy, including 44% complete response (CR)/near CR (nCR); at retreatment, ≥PR rate was 46%, including 15% CR/nCR. Median progression-free survival was 11.4 months (95% confidence interval [CI]: 9.1-12.7) from start of initial bortezomib treatment and 6.4 months (95% CI: 4.4-7.2) from start of retreatment. Median overall survival from start of retreatment was 17.6 months (95% CI: 14.4-23.5). Of the 96 patients retreated with bortezomib, 77% reported an AE. Peripheral neuropathy during bortezomib retreatment occurred in 49% of patients, including 10% grade 3/4.

Conclusion: These data suggest that retreatment with bortezomib is a feasible option for patients with relapsed/refractory MM.
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http://dx.doi.org/10.1002/hsr2.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346989PMC
January 2019

Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial.

Lancet Haematol 2018 Oct;5(10):e479-e492

Department of Haematology, VU University Medical Centre, VU University Amsterdam, Amsterdam, Netherlands.

Background: In patients with recently diagnosed multiple myeloma, the HOVON-50 phase 3 trial showed improved event-free survival for thalidomide-containing induction and maintenance regimens (in conjunction with high-dose melphalan and autologous stem cell transplantation [auto-SCT]) after a median of 52 months of follow-up, by comparison with regimens containing classical cytotoxic drugs. In this follow-up analysis, we aimed to determine the long-term effects of thalidomide in induction and maintenance therapy in multiple myeloma.

Methods: In this open-label, phase 3 randomised controlled trial, patients with recently diagnosed multiple myeloma were recruited from 44 Dutch and Belgian hospitals. Participants had been diagnosed with multiple myeloma of Durie-Salmon stage II or III and were aged 18-65 years. Patients were randomly assigned (1:1) either to receive three 28-day cycles of vincristine (0·4 mg, intravenous rapid infusion on days 1-4), doxorubicin (9 mg/m, intravenous rapid infusion on days 1-4) and dexamethasone (40 mg, orally on days 1-4, 9-12, and 17-20; control group); or to receive the same regimen, but with thalidomide (200-400 mg, orally on days 1-28) instead of vincristine (thalidomide group). No masking after assignment to intervention was used. Patients were randomly assigned to groups, stratified by centre and treatment policy (one vs two courses of high-dose melphalan and auto-SCT). After stem cell harvest, patients received one or two courses of 200 mg/m melphalan intravenously with auto-SCT. Patients with at least a partial response to high-dose melphalan and auto-SCT were eligible for maintenance therapy, starting 2-3 months after high-dose melphalan. Patients in the control group received maintenance therapy with interferon alfa (3 ×  10 international units, subcutaneously, three times weekly). Patients in the thalidomide group received thalidomide as maintenance therapy (50 mg, orally, daily). Maintenance therapy was given until relapse, progression, or the occurrence of adverse events. The primary endpoint of the study was event-free survival (EFSc; censored at allogeneic stem cell transplantation), analysed by intention to treat. The study is closed for enrolment and this Article represents the final analysis. This trial was registered with the Netherlands Trial Register, number NTR238.

Findings: Between Nov 27, 2001 and May 31, 2005, 556 patients were enrolled in the study, of whom 536 (96%) were eligible for evaluation and were randomly allocated (268 [50%] to the control group and 268 [50%] to the thalidomide group). These 536 patients were assessed for the primary endpoint of EFSc. At an extended median follow-up of 129 months (IQR 123-136), EFSc was significantly longer in the thalidomide group compared with the control group (multivariate analysis hazard ratio [HR] 0·62, 95% CI 0·50-0·77; p<0·0001). Thalidomide maintenance was stopped because of toxicity in 65 (42%) of 155 patients in the thalidomide group (neuropathy in 49 [75%] patients, skin reactions in four [6%] patients, fatigue in two [3%] patients, and as other symptoms [such as abdominal pain, pancreatitis, and dyspnoea] in ten [15%] patients). 24 (27%) of 90 patients in the control group discontinued protocol treatment during maintenance therapy with interferon alfa because of toxicity (five [21%] patients with psychiatric side-effects, five [21%] patients with flu-like symptoms, four [17%] patients with haematological toxicity [thrombocytopenia and leucocytopenia], three [13%] patients with skin reactions, and seven [29%] patients with other symptoms [such as infections, cardiomyopathy, and headache]). The frequency of second primary malignancies was similar in both groups. There were 23 second primary malignancies in 17 patients in the control group and 29 second primary malignancies in 24 patients in the thalidomide group. There were 19 treatment-related deaths in the control group, and 16 treatment-related deaths in the thalidomide group.

Interpretation: Our data indicate that thalidomide-based treatment could be a treatment option for patients with multiple myeloma who are eligible for auto-SCT who live in countries without access to proteasome inhibitors or lenalidomide. However, careful follow-up and timely dose adjustments are important to prevent the development of thalidomide-induced neurotoxicity.

Funding: The Dutch Cancer Foundation.
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http://dx.doi.org/10.1016/S2352-3026(18)30149-2DOI Listing
October 2018

European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when.

Haematologica 2018 11 31;103(11):1772-1784. Epub 2018 Aug 31.

Department of Medicine I, Hematology, Oncology & Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Germany.

The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histopathological, and radiological markers of disease. Specific tests are needed both at presentation and during follow-up in order to reach the correct diagnosis and characterize the disease precisely. These tests can also serve prognostic purposes and are useful for follow-up of myeloma patients. Molecular analyses remain pivotal for defining high-risk myeloma and are used in updated patient stratifications, while minimal residual disease assessment via flow cytometry, molecular techniques and radiological approaches provides additional prognostic information on patients' long-term outcome. This pivotal information will guide our future treatment decisions in forthcoming clinical trials. The European Myeloma Network group updated their guidelines on different diagnostic recommendations, which should be of value to enable appropriate use of the recommendations both at diagnosis and during follow-up.
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http://dx.doi.org/10.3324/haematol.2018.189159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278986PMC
November 2018

Bortezomib-based therapy for relapsed/refractory multiple myeloma in real-world medical practice.

Eur J Haematol 2018 Oct 5;101(4):556-565. Epub 2018 Sep 5.

Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.

Objective: The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice.

Method: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization.

Results: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (≥partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months' median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment.

Conclusion: These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.
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http://dx.doi.org/10.1111/ejh.13147DOI Listing
October 2018

Secondary plasma cell leukemia: a multicenter retrospective study of 101 patients.

Leuk Lymphoma 2019 01 2;60(1):118-123. Epub 2018 Jul 2.

ab John Theurer Cancer Center, Myeloma Division , Hackensack University Medical Center , Hackensack , NJ , USA.

This multicenter retrospective study included 101 patients (median age 62 years) with secondary plasma cell leukemia (sPCL). The median time from initial multiple myeloma diagnosis to sPCL was 31 months. Fifty-five out of 72 patients (75%) who received any therapy were treated with immunomodulators (IMiDs) and/or proteasome inhibitors (PIs), and 14/72 (19%) underwent salvage autologous stem cell transplantation (ASCT). The overall response rate in patients who received ASCT or PI (either alone or in combination) was higher than in those who did not (93% vs. 36% and 60% vs. 30%, respectively). The median overall survival (OS) in patients who received therapy was 4.2 months (95% CI: 1.3; 8.0) with a 1-year OS of 19%. Platelet count ≤100 × 10/L at sPCL diagnosis was the only independent predictor of a poorer OS in treated patients (HR = 3.98, p = .0001). These findings suggest that patients with sPCL may benefit from salvage ASCT- and PI-based regimens.
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http://dx.doi.org/10.1080/10428194.2018.1473574DOI Listing
January 2019