Publications by authors named "Gian Matteo Pica"

11 Publications

  • Page 1 of 1

Subcutaneous Rituximab-MiniCHOP Compared With Subcutaneous Rituximab-MiniCHOP Plus Lenalidomide in Diffuse Large B-Cell Lymphoma for Patients Age 80 Years or Older.

J Clin Oncol 2021 Apr 14;39(11):1203-1213. Epub 2021 Jan 14.

Department of Hematology, Centre Henri Becquerel, UNIROUEN, University of Normandy, INSERM U1245, Rouen, France.

Purpose: The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy-cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)-is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non-germinal center B-cell-like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2-miniCHOP.

Patients And Methods: Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS).

Results: A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2-miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, = .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2-miniCHOP.

Conclusion: The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population.
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http://dx.doi.org/10.1200/JCO.20.02666DOI Listing
April 2021

Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study.

Blood Adv 2020 08;4(14):3217-3223

Département d'Hématologie, Equipe d'Accueil 7365, CHU Lille, Lille, France.

Complete molecular response (CMR) after first-line immunochemotherapy reflects treatment efficacy and may predict prognosis in patients with follicular lymphoma (FL). RELEVANCE is the first phase 3 trial comparing the chemotherapy-free regimen lenalidomide/rituximab (R2) vs rituximab/chemotherapy (R-Chemo) in previously untreated FL patients (ClinicalTrials.gov identifier: NCT01650701). The objective of the minimal residual disease (MRD) analysis was to determine the ability of a chemotherapy-free regimen to induce CMR. Of 440 French patients participating in the Lymphoma Study Association (LYSA) RELEVANCE MRD study, all 222 patients with a BIOMED-2-detectable BCL2-JH translocation at diagnosis were analyzed. MRD was quantified by droplet digital polymerase chain reaction with a sensitivity ≤10-4. At week 24 (end of induction treatment), 98% and 78% of patients achieved CMR in peripheral blood (PB) and bone marrow (BM), respectively. Achievement of CMR (in PB and/or BM) had a significant impact on progression-free survival (PFS), with 3-year PFS of 84% and 55% for patients with CMR and detectable MRD, respectively (P = .015). CMR at week 24 was reached more frequently in the R2 arm (105/117; 90%) than in the R-Chemo arm (70/90; 77%) (P = .022). The poor prognostic value in terms of PFS for the persistence of molecular disease was observed irrespective of treatment arm (interaction test, P = .31). In agreement with the clinical results of the RELEVANCE trial, our results show that R2 immunomodulatory treatment in first-line FL can achieve high rates of CMR.
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http://dx.doi.org/10.1182/bloodadvances.2020001955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391139PMC
August 2020

[Carfilzomib-induced haemolytic and uremic syndrome: Favorable outcome with eculizumab].

Nephrol Ther 2020 Jul 19;16(4):221-224. Epub 2020 Jun 19.

Service de néphrologie-dialyse, centre hospitalier Métropole Savoie, place Lucien Biset, 73000 Chambéry, France.

Thrombotic microangiopathies are rare diseases characterized by an initial endothelial injury and the formation of thrombi in the microcirculation. Several types of thrombotic microangiopathies can be distinguished: the thrombotic thrombocytopenic purpura; the hemolytic and uremic syndrome, mainly "typical" following a shiga toxin-producing Escherichia coli infection or "atypical" due to a dysregulation of the alternative complement pathway; and "secondary" thrombotic microangiopathies. The use of drug treatments is reported as a frequent cause in this last category and requires stopping the offending drug. We report the case of a patient who developed "secondary" hemolytic and uremic syndrome associated with carfilzomib, a proteasome inhibitor which is used in case of multiple myeloma relapses. Besides stopping the treatment, the patient still showed signs of hemolysis and renal failure with anuria requiring hemodialysis. An eculizumab treatment was therefore initiated. The overall evolution was favorable and an improvement of the renal function promptly allowed the discontinuation of hemodialysis. We discuss the mechanisms that may activate the alternative complement pathway and the potential interest of a transient use of eculizumab in case of carfilzomib-induced hemolytic and uremic syndrome.
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http://dx.doi.org/10.1016/j.nephro.2020.03.006DOI Listing
July 2020

High total metabolic tumor volume at baseline predicts survival independent of response to therapy.

Blood 2020 04;135(16):1396-1405

Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Hemato-Oncology, Paris, France; and.

Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase 3 REMARC study that randomized responding patients to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) into maintenance lenalidomide or placebo. TMTV was computed on baseline positron emission tomography/computed tomography using the 41% maximum standardized uptake value method; the optimal TMTV cutoff for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301 out of 650 evaluable patients, including 192 patients classified as germinal center B-cell-like (GCB)/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3; optimal TMTV cutoff was 220 cm3. Patients with high vs low TMTV showed worse/higher Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, stage III or IV disease, >1 extranodal site, elevated lactate dehydrogenase, International Prognostic Index (IPI) 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS and OS, independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients, after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population. This trial was registered at www.clinicaltrials.gov as #NCT01122472.
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http://dx.doi.org/10.1182/blood.2019003526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162688PMC
April 2020

Lenalidomide maintenance for diffuse large B-cell lymphoma patients responding to R-CHOP: quality of life, dosing, and safety results from the randomised controlled REMARC study.

Br J Haematol 2020 04 8;189(1):84-96. Epub 2019 Nov 8.

Paracelsus Medical University Salzburg, Salzburg Cancer Research Institute, Salzburg, Austria.

Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) responding to induction chemotherapy in the phase 3 REMARC study. This subpopulation analysis assessed the impact of lenalidomide maintenance and treatment-emergent adverse events (TEAEs) on health-related quality of life (HRQOL). Global health status (GHS), and physical functioning and fatigue subscales were evaluated in patients who completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-C30 v3.0. The impact of TEAEs classified post hoc as subjective (patients can feel) or observable (only measurable by physicians) on dose reductions and discontinuations was assessed. Among 457 patients (lenalidomide, n = 229; placebo, n = 228), mean (standard deviation) GHS was similar between treatment arms [68·2 (20·7) Versus 72·0 (17·8)] at randomisation and remained similar during maintenance. Patients receiving lenalidomide experienced no meaningful changes in GHS, physical functioning, or fatigue. Observable TEAEs were more common (81·1% Versus 66·3%) and more likely to lead to dose reductions, than subjective TEAEs in both arms. PFS was superior in the lenalidomide arm regardless of dose reduction. Lenalidomide maintenance prolonged PFS and did not negatively impact HRQOL in patients with DLBCL despite TEAEs being more common, when compared with placebo.
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http://dx.doi.org/10.1111/bjh.16300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154674PMC
April 2020

Safety and efficacy findings from the open-label, multicenter, phase 3b, expanded treatment protocol study of ruxolitinib for treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea and for whom no alternative treatments are available.

Leuk Lymphoma 2019 12 30;60(14):3493-3502. Epub 2019 Jul 30.

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

Ruxolitinib was recently approved for the treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea based on data from the RESPONSE studies. This phase 3b, Expanded Treatment Protocol study (NCT02292446) of ruxolitinib for hydroxyurea-resistant/intolerant patients with polycythemia vera ( = 161: median exposure = 25.1 weeks) further evaluated the safety of ruxolitinib. Adverse events (AEs) led to dose adjustment/interruption in 37.9% of patients and study drug discontinuation in 8.7% of patients. The most common hematologic AEs included anemia and thrombocytosis; while headache and diarrhea were the most frequent nonhematologic AEs. At week 24, 45.3% of patients achieved hematocrit control; hematologic remission was seen in 18% of patients. At least, 50% of reduction in spleen length was achieved in 86.7% of patients from baseline at any time. The observed safety profile of ruxolitinib was consistent and the efficacy results were similar to the observed values in the RESPONSE studies.
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http://dx.doi.org/10.1080/10428194.2019.1636985DOI Listing
December 2019

Dyserythropoiesis evaluated by the RED score and hepcidin:ferritin ratio predicts response to erythropoietin in lower-risk myelodysplastic syndromes.

Haematologica 2019 03 4;104(3):497-504. Epub 2018 Oct 4.

Department of Hematology, CHU Grenoble-Alpes, Grenoble.

Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level <10 g/dL. Patients could be red blood cell transfusion-dependent or not and were given epoetin zeta 40 000 IU/week. Serum erythropoietin level, iron parameters, hepcidin, flow cytometry Ogata and RED scores, and growth-differentiation factor-15 levels were determined at baseline, and molecular analysis by next-generation sequencing was also conducted. Erythroid response (defined according to the International Working Group 2006 criteria) was assessed at week 12. Seventy patients, with a median age of 78 years, were included in the study. There were 22 patients with refractory cytopenia with multilineage dysplasia, 19 with refractory cytopenia with unilineage dysplasia, 14 with refractory anemia with ring sideroblasts, four with refractory anemia with excess blasts-1, six with chronic myelomonocytic leukemia, two with del5q-and three with unclassifiable myelodysplastic syndrome. According to the revised International Prognostic Scoring System, 13 had very low risk, 47 had low risk, nine intermediate risk and one had high-risk disease. Twenty patients were transfusion dependent. Forty-eight percent had an erythroid response and the median duration of the response was 26 months. At baseline, non-responders had significantly higher RED scores and lower hepcidin:ferritin ratios. In multivariate analysis, only a RED score >4 (=0.05) and a hepcidin:ferritin ratio <9 (=0.02) were statistically significantly associated with worse erythroid response. The median response duration was shorter in patients with growth-differentiation factor-15 >2000 pg/mL and a hepcidin:ferritin ratio <9 (=0.0008 and =0.01, respectively). In multivariate analysis, both variables were associated with shorter response duration. Erythroid response to epoetin zeta was similar to that obtained with other erythropoiesis-stimulating agents and was correlated with higher baseline hepcidin:ferritin ratio and lower RED score. .
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http://dx.doi.org/10.3324/haematol.2018.203158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395339PMC
March 2019

Myelofibrosis and acquired hemophilia A: a case report.

J Med Case Rep 2016 May 7;10(1):115. Epub 2016 May 7.

Service of Hematology, Centre Hospitalier Metropole Savoie, 73011, Chambéry, France.

Background: Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described.

Case Presentation: A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy.

Conclusions: Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.
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http://dx.doi.org/10.1186/s13256-016-0897-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859983PMC
May 2016

Safety and efficacy of (90) yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients. An Italian cooperative study.

Br J Haematol 2014 Mar 17;164(5):710-6. Epub 2013 Dec 17.

U.O. Ematologia 1, IRCCS AOU San Martino-IST, Genova, Italy.

(90) Yttrium ((90) Y)-Ibritumomab-Tiuxetan combines the targeting advantage of a monoclonal antibody with the radiosensitivity of Follicular Lymphoma (FL). Previous studies showed that 90Y-IT is safe and effective in relapsed/refractory indolent FL, irrespective of prior treatment with rituximab. This multicentre trial aimed to evaluate the safety and the efficacy of "upfront" single-agent ((90) Y)-Ibritumomab-Tiuxetan in advanced-stage FL. The primary objective was the incidence of responses in terms of complete (CR) and partial remission (PR). Fifty patients with stage II "bulky", III or IV FL received a single treatment course with ((90) Y)-Ibritumomab-Tiuxetan as initial therapy. The median age was 60 years. Bone marrow involvement (<25%) was observed in 24 patients (48%) and 7 (14%) had an elevated lactate dehydrogenase level. The overall response (ORR) and CR rates were 94% and 86%, respectively with a median follow-up of 38·8 months. The median progression-free survival (PFS) was not reached, whereas the 3-year estimated PFS and overall survival (OS) rate was 63·4% and 90%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 30% and 26% of patients respectively; none experienced grade 3/4 non-haematological toxicity. No cases of secondary haematological malignancies were observed. ((90) Y)-Ibritumomab-Tiuxetan was demonstrated to be highly effective and safe as first-line treatment for advanced-stage FL.
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http://dx.doi.org/10.1111/bjh.12695DOI Listing
March 2014

Nucleophosmin gene-based monitoring in de novo cytogenetically normal acute myeloid leukemia with nucleophosmin gene mutations: comparison with cytofluorimetric analysis and study of Wilms tumor gene 1 expression.

Leuk Lymphoma 2012 Nov 21;53(11):2214-7. Epub 2012 May 21.

Department of Hematology and Oncology , IRCCS Azienda Ospedaliera Universitaria S. Martino-IST, Genova, Italy.

We compared the clinical value of minimal residual disease (MRD) monitoring by cytofluorimetric methods, Wilms tumor gene 1 (WT1) expression and the study of nucleophosmin gene (NPM) mutations in a series of 26 patients with NPM-mutated de novo acute myeloid leukemia (NPM-AML) who achieved complete hematological remission after conventional chemotherapy. The relapse risk was significantly lower only in patients achieving a NPM molecular complete response (NPM mol-CR) and confirmed NPM mol-CR (non-detectable NPM mutations in two consecutive marrow samples). The disease-free survival (DFS) of patients achieving a < 4-log or ≥ 4-log reduction in NPM value after induction therapy was 12.6 % and 50%, respectively, at 36 months (p = 0.009). The attainment of a confirmed NPM-CR had a significant influence on overall survival (OS at 36 months was 64.3% and 11.9% in patients obtaining or not obtaining confirmed NPM-CR, respectively, p < 0.03). We confirm that NPM-molecular relapse (NPM-rel) is always followed by hematological relapse (H-rel), but longitudinal studies of NPM mutations may predict an impending H-rel earlier than flow cytometric- or WT1-based methods.
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http://dx.doi.org/10.3109/10428194.2012.681658DOI Listing
November 2012

Bortezomib plus dexamethasone is highly effective in relapsed and refractory myeloma patients but responses are short-lived.

Eur J Haematol 2009 Nov 10;83(5):449-54. Epub 2009 Jun 10.

Division of Hematology, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Objectives: Bortezomib has proven to be effective as single agent in myeloma patients. Aim of this study was to evaluate the efficacy and toxicity of bortezomib in combination with dexamethasone in a cohort of multiple myeloma (MM) relapsed/refractory patients treated in a single center.

Patients And Methods: In this single center study, 70 patients were treated with bortezomib alone (9) or in combination with dexamethasone (61).

Results: Forty-one patients (59%) achieved at least a partial response (PR), including 7% complete response (CR), 36% very good partial response (VGPR) reaching the best response within four cycles. The duration of response was significantly longer for patients achieving CR/VGPR than for those achieving PR (7.3 vs. 3.8 months, P = 0.03). Likewise, time to progression, time to alternative treatment, and treatment free interval were significantly better for patients obtaining CR/VGPR (6.8, 9.4, 6.5 months respectively) as compared with PR (4.9, 6.3, 2 months respectively). The only dose-limiting toxicity was peripheral neuropathy (PN), which occurred in 38/70 patients (55%) and was of grade 3-4 in 12 (17%). PN led to a dose reduction or treatment discontinuation in 17 (24%) patients. Complete resolution or improvement of PN occurred in 29/38 (76%) after a median time of 100 d (range: 17-202).

Conclusions: Bortezomib in combination with dexamethasone is highly effective in relapsed/refractory MM producing an impressive rate of CR/VGPR, but responses are short-lived.
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http://dx.doi.org/10.1111/j.1600-0609.2009.01295.xDOI Listing
November 2009
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