Publications by authors named "Alain Kentos"

18 Publications

  • Page 1 of 1

Ixazomib, Daratumumab, and Low-Dose Dexamethasone in Frail Patients With Newly Diagnosed Multiple Myeloma: The Hovon 143 Study.

J Clin Oncol 2021 Sep 4;39(25):2758-2767. Epub 2021 May 4.

Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.

Purpose: Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex).

Methods: Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years.

Results: The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles.

Conclusion: Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.03143DOI Listing
September 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17843286.2020.1860411DOI Listing
December 2020

Reply to M. Lambertini et al.

J Clin Oncol 2017 03 28;35(7):805-806. Epub 2016 Nov 28.

Isabelle Demeestere, Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium; Pauline Brice, St Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Fedro A. Peccatori, European Institute of Oncology, Milan, Italy; Alain Kentos, Jolimont Hospital, Haine-Saint-Paul, Belgium; Jehan Dupuis, Henri Mondor Hospital, Paris, France; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerp, Belgium; Rene-Olivier Casasnovas, Centre Hospitalier Universitaire Dijon, Dijon, France; Eric Van Den Neste, Cliniques Universitaires Université Catholique de Louvain Saint-Luc, Brussels, Belgium; Julie Dechene, Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium; Viviane De Maertelaer, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Belgium; Dominique Bron, J. Bordet Institute, Brussels, Belgium; and Yvon Englert, Research Laboratory on Human Reproduction, Université Libre de Bruxelles, and Erasme Hospital, Brussels, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2016.70.6093DOI Listing
March 2017

No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial.

J Clin Oncol 2016 08 23;34(22):2568-74. Epub 2016 May 23.

Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.

Purpose: We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up.

Patients And Methods: A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up.

Results: Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467).

Conclusion: To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2015.65.8864DOI Listing
August 2016

The role of rituximab in adults with warm antibody autoimmune hemolytic anemia.

Blood 2015 May 31;125(21):3223-9. Epub 2015 Mar 31.

Department of Hematology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium.

Warm antibody hemolytic anemia is the most common form of autoimmune hemolytic anemia. When therapy is needed, corticosteroids remain the cornerstone of initial treatment but are able to cure only a minority of patients (<20%). Splenectomy is usually proposed when a second-line therapy is needed. This classical approach is now challenged by the use of rituximab both as second-line and as first-line therapy. Second-line treatment with rituximab leads to response rates similar to splenectomy (∼70%), but rituximab-induced responses seem less sustained. However, additional courses of rituximab are most often followed by responses, at the price of reasonable toxicity. In some major European centers, rituximab is now the preferred second-line therapy of warm antibody hemolytic anemia in adults, although no prospective study convincingly supports this attitude. A recent randomized study strongly suggests that in first-line treatment, rituximab combined with steroids is superior to monotherapy with steroids. If this finding is confirmed, rituximab will emerge as a major component of the management of warm antibody hemolytic anemia not only after relapse but as soon as treatment is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2015-01-588392DOI Listing
May 2015

Diagnosis and follow-up of monoclonal gammopathies of undetermined significance; information for referring physicians.

Ann Med 2013 Sep 14;45(5-6):413-22. Epub 2013 Jun 14.

CHU de Liège, Belgium.

The prevalence of monoclonal gammopathy of undetermined significance (MGUS) is generally estimated at 3.4% in the general population over 50 years, and its incidence increases with age. MGUS represents a preneoplastic entity that can transform into multiple myeloma or other lymphoproliferative disorders. The risk of malignant transformation is estimated at 1% per year and persists over time. Predictors of malignant transformation have been identified such as the heavy chain isotype, The level of monoclonal proteins, increasing levels of the monoclonal component during the first years off follow-up, the percentage of bone marrow plasmocytosis, the dosage of serum free light chains, the presence of immunophenotypically abnormal plasma cells, aneuploidy, and the presence of circulating plasma cells. Prognostic scores that combine certain of these factors have been proposed and allow the identification of high-risk patients. Their use could assist in tailoring the care for each patient, based on his/her risk profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/07853890.2013.801562DOI Listing
September 2013

Gonadotropin-releasing hormone agonist for the prevention of chemotherapy-induced ovarian failure in patients with lymphoma: 1-year follow-up of a prospective randomized trial.

J Clin Oncol 2013 Mar 5;31(7):903-9. Epub 2012 Nov 5.

Universite´ Libre de Bruxelles, Belgium.

Purpose: To assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in preventing chemotherapy-induced ovarian failure in patients treated for Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized, prospective trial.

Patients And Methods: Patients age 18 to 45 years were randomly assigned to receive either the GnRHa triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) concomitantly with alkylating agents containing chemotherapy. The primary end point was the premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] ≥ 40 IU/L) after 1 year of follow-up.

Results: Eighty-four of 129 randomly assigned patients completed the 1-year follow-up. The mean FSH values were higher in the control group than in the GnRHa group during chemotherapy; however, this difference was no longer observed after 6 months of follow-up. After 1 year, 20% and 19% of patients in the GnRHa and control groups, respectively, exhibited POF (P = 1.00). More than half of patients in each group completely restored their ovarian function (FSH < 10 IU/L), but the anti-Müllerian hormone values were higher in the GnRHa group than in the control group (1.4 ± 0.35 v 0.5 ± 0.15 ng/mL, respectively; P = .040). The occurrence of adverse events was similar in both groups with the exception of metrorrhagia, which was more frequently observed in the control group than the GnRHa group (38.4% v 15.6%, respectively; P = .024).

Conclusion: Approximately 20% of patients in both groups exhibited POF after 1 year of follow-up. Triptorelin was not associated with a significant decreased risk of POF in young patients treated for lymphoma but may provide protection of the ovarian reserve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2012.42.8185DOI Listing
March 2013

Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone.

Blood 2010 Nov 13;116(19):3743-50. Epub 2010 Jul 13.

Centre René Gauducheau, Nantes/St Herblain, France.

The phase 3 Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone study in newly diagnosed multiple myeloma patients ineligible for high-dose therapy demonstrated that bortezomib-melphalan-prednisone (VMP) was superior to melphalan-prednisone across all efficacy end points. We assessed the prognostic impact of response on time-to-event parameters in the intent-to-treat population. Patients received nine 6-week cycles of treatment. Time to progression, time to next therapy, and treatment-free interval were associated with quality of response. When European Group for Blood and Marrow Transplantation criteria were used, complete response (CR) was associated with significantly longer time to progression (hazard ratio [HR] = 0.45, P = .004), time to next therapy (HR = 0.46, P = .0004), and treatment-free interval (HR = 0.38, P < .0001) versus partial response, but there was no significant difference in overall survival (HR = 0.87, P = .54); similar differences were seen with CR versus very good partial response by uniform criteria. Quality of response improved with prolonged VMP treatment, with 28% of CRs achieved during cycles 5-9. CR duration appeared similar among patients with "early" (cycles 1-4) and "late" CRs (cycles 5-9) and among patients receiving 9 versus < 9 cycles of bortezomib within VMP. These results highlight that CR is an important treatment goal and support prolonged VMP therapy to achieve maximal response. This study is registered at http://www.clinicaltrials.gov as NCT00111319.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2010-03-275800DOI Listing
November 2010

Distal acquired demyelinating symmetric neuropathy associated with anti-GM1 antibodies: is this a CIDP variant?

Acta Neurol Belg 2010 Mar;110(1):103-6

Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Distal acquired demyelinating symmetric (DADS) neuropathy is clinically characterised by distal motor and sensory disturbances. Typically DADS does not respond or responds poorly to intravenous immunoglobulins (IVIg). We report the case of a 58-year-old patient who developed distal paraparesis. Serum electrophoresis demonstrated monoclonal IgM paraproteinemia having an anti-GM1 but no anti-MAG activity. Conduction velocities showed demyelinating pattern. Work-up excluded a lymphoproliferative disorder After IVIg treatment we observed a clinical and neurophysiological improvement. Regarding these peculiar findings, we suggest that DADS needs to be splitted in several forms determined among others by clinical, neurophysiological and antiganglioside profile and therapeutic response. We advocate to perform systematic antiganglioside antibodies assay additionnaly to anti-MAG when DADS is suspected in order to improve dysimmune neuropathies classification.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2010

An estimation of the incidence and demographic picture of the major hemoglobinopathies in Belgium (from a confidential inquiry).

Hemoglobin 2008 ;32(3):279-85

Department of Clinical Chemistry, Cliniques Universitaires de Bruxelles, Hopital Erasme, Universite Libre de Bruxelles, Bruxelles, Belgium.

An estimation of the incidence and demographic picture of the major hemoglobinopathies in Belgium has been approached through a confidential inquiry sent to 228 pediatric and adult hematological departments. Forty-two percent of responses showed that 417 patients are known in Belgium: 83% with sickle cell disease, 13% with beta-thalassemia (beta-thal) major, 2% with beta-thal intermedia, and 1% with Hb H disease. Twenty-five percent of the sickle cell disease patients and 54% of those suffering from a beta-thal major were older than 20 years. Three hospitals ensure the follow-up of 70% of the patients and are situated in Brussels, Belgium; a follow-up of less than 20 patients was reported at 21 centers. These results confirm that sickle cell disease is the major hemoglobinopathy in Belgium; it concerns mostly pediatricians but adult hematologists are also confronted with these pathologies. Therefore, it is necessary to implement integrated programs of prevention and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03630260802004400DOI Listing
August 2008

Valproic acid induces apoptosis in chronic lymphocytic leukemia cells through activation of the death receptor pathway and potentiates TRAIL response.

Exp Hematol 2007 Oct 13;35(10):1527-37. Epub 2007 Aug 13.

Experimental Hematology, Bordet Institute, ULB, Brussels, Belgium.

Objective: Chronic lymphocytic leukemia (CLL) cells develop chemoresistance over time associated with defects in apoptosis pathway. Novel treatment strategies are required to overcome resistance of cells to commonly used agents. The effects of valproic acid (VPA), an antiepileptic drug with histone deacetylase inhibitory activity, on mononuclear cells isolated from 40 CLL patients were evaluated.

Methods: CLL cells were treated with increasing doses of VPA (0.5, 1, 2, and 5 mM). The mode of cytotoxic drug action was determined by annexin binding, DNA fragmentation, and caspase activation.

Results: Exposure of CLL cells to VPA resulted in dose-dependent cytotoxicity and apoptosis in the 40 CLL patients. VPA treatment induced apoptotic changes in CLL cells including phosphatidylserine externalization and DNA fragmentation. The mean apoptotic rates were similar between IgV(H) mutated and unmutated patients, the latter presenting a more aggressive clinical course. VPA induced apoptosis via the extrinsic pathway involving engagement of the caspase-8-dependent cascade. Although CLL cells are commonly resistant to death receptor-induced apoptosis, VPA significantly increased sensitivity of leukemic cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and led to downregulation of c-FLIP (L) expression. VPA caused no potentialization of TRAIL-induced apoptosis on normal B cells. In addition, VPA overcame the prosurvival effects of bone marrow stromal cells.

Conclusion: These findings point out that the combination of TRAIL and VPA, at clinically relevant concentration, may be valuable in the treatment of CLL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exphem.2007.06.014DOI Listing
October 2007

Post-transplant lymphoproliferative disorders after lung transplantation: first-line treatment with rituximab may induce complete remission.

Clin Transplant 2006 Mar-Apr;20(2):179-87

Department of Chest Medicine, Erasme University Hospital, Brussels, Belgium.

Background: Post-transplant lymphoproliferative disorders (PTLD) are potentially lethal complications of solid organ transplantation. We, here, report on our experience with rituximab, an anti-CD20 monoclonal antibody, as first-line treatment for PTLD in six lung transplant recipients.

Patients And Methods: Two of the patients developed PTLD during the first year after transplantation, while four developed late-onset PTLD. One patient presented with PTLD localized to the graft, one had unilateral cervical lymph nodes, and the others presented with multi-organ involvement. All patients had diffuse large B-cell lymphoma. Immunosuppressive therapy was reduced and rituximab was administered at a dose of 375 mg/m(2)/wk for 4 wk.

Results: One patient did not respond to the first two courses of rituximab, received conventional chemotherapy, and achieved complete remission; four patients achieved complete remission after four courses with a median relapse-free survival of 34 months (range: 14-55); and one patient did not respond and died. The diagnosis of complete remission was established by conventional imaging techniques combined to whole-body positron emission tomography scan.

Conclusions: We conclude that reduction in immunosuppression combined to first-line treatment with rituximab may induce long-term complete remission in lung transplant recipients presenting PTLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1399-0012.2005.00462.xDOI Listing
October 2006

Circulating thrombopoietin as an in vivo growth factor for blast cells in acute myeloid leukemia.

Blood 2006 Mar 29;107(6):2525-30. Epub 2005 Nov 29.

Laboratory of Hematology, CHU-Brugmann, 4 Place Van Gehuchten, B-1020 Brussels, Belgium.

Thrombopoietin (TPO), the major growth factor for cells of the megakaryocytic lineage, is removed from circulation by binding to c-mpl receptors present on platelets and megakaryocytes. We studied patients with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) and used TPO-induced c-fos protein up-regulation as a marker of c-mpl functionality and observed that c-mpl-presenting blast cells were present in 62% (37 of 60) of patients with ALL but that c-mpl was nonfunctional in 0 of 28 patients and that they were present in 56% (22 of 39) of patients with AML and were functional in 43% (12 of 28). Adequate increases in serum TPO level in response to thrombocytopenia were seen in patients with ALL and with c-mpl-deficient (c-mpl-) AML. In contrast, in patients with c-mpl-proficient (c-mpl+) AML, TPO levels were found to be inappropriately low but increased to expected values during induction chemotherapy as blasts disappeared. In vitro significant TPO-associated blast cell proliferation or decreased apoptosis was observed only in patients with c-mpl+ AML compared with ALL or c-mpl- AML and was highly correlated with low in vivo TPO levels (P < .001). These data suggest that, in patients with AML, inadequate TPO levels are secondary to TPO clearing by functional c-mpl receptor myeloid blast cells and that TPO may serve as an in vivo myeloid leukemic growth factor in a significant number of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2005-06-2552DOI Listing
March 2006

Atypical recurrent varicella in 4 patients with hemopathies.

J Am Acad Dermatol 2003 Mar;48(3):442-7

Department of Dermatopathology, University Medical Center of Liâgege, Belgium.

Relapsing varicella may occur in children with HIV infection and more rarely in younger adults. Our aim was to report unusual clinical, histologic, and virologic aspects of 4 elderly patients with malignant hemopathies who had an unusual form of recurrent varicella develop. Conventional microscopy, immunohistochemistry, and in situ hybridization were applied to smears and skin biopsy specimens. The patients presented a few dozen, scattered, large, papulovesicular lesions with central crusting. No zoster-associated pain or dermatomal distribution of the lesions was noted. Conventional microscopy revealed vascular changes and epidermal alterations typical for alpha-herpes virus infection. The varicella zoster virus major viral envelope glycoproteins gE and gB, and the immediate-early varicella zoster virus IE63 protein and the corresponding genome sequence for gE were detected on Tzanck smears; they were localized in endothelial cells and keratinocytes on skin biopsy specimens. The varicella zoster virus infection in endothelial cells, the vascular involvement, and the widespread distribution of the lesions suggest that the reported eruptions are vascular rather than neural in origin. These findings invalidate the diagnosis of herpes zoster but strongly support the diagnosis of recurrent varicella in an indolent and yet unreported presentation. Furthermore, these eruptions differ from relapsing varicella in children and young adults by the age of the patients, the paucity of clinical lesions, the larger diameter of the lesions and their peculiar clinical aspect, the significantly longer time interval between primary varicella and the recurrence, the prolonged healing time of the lesions, their mild disease course, and the fact that all the lesions are in the same stage of development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1067/mjd.2003.94DOI Listing
March 2003

Polyclonal coagulase-negative staphylococcal catheter-related bacteremia documented by molecular identification and typing.

Clin Microbiol Infect 1999 Apr;5(4):224-227

Laboratoire de Microbiologie, Hopital Erasme, 808, Route de Lennik, 1070 Brussels, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1469-0691.1999.tb00128.xDOI Listing
April 1999
-->