Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study

Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety of BM in a real-world setting in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least three lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range, 37–82) years. High-risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was five (range, 3–12). The median number of BM cycles administered was three (range, 1–22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95% confidence interval [CI]: 5.9-15.3), and median progression-free survival was 3.5 months (95% CI: 1.9-4.7). The median duration of response was 9 months (range, 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population

Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML

International audienceObjectives: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection.Materials and methods: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement.Results: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response.Conclusion: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML

Isolated intra-ocular relapses of primary central nervous system lymphoma

Abstract published in European Journal of Neurology 24(Suppl 1):52, 2017International audienceBackground and aims: Relapses in primary central nervous system lymphoma (PCNSL) are usually cerebral and severe. Isolated intraocular relapses (IIOR) are much rarer and have not been specifically studied so far.Methods: We retrospectively selected patients treated within the French national expert network on PCNSL (LOC network). The inclusion criteria were: histologically proven PCNSL with at least a cerebral localization, immunocompetent status, 1st line treatment based on high-dose methotrexate and isolated IIOR subsequently.Results: 47 patients met the inclusion criteria (median age: 64.5 years (32.8-79.7), median Karnofsky Performance Status (KPS): 70 (40-100)). Initially, 13 patients had an ocular involvement, 16 had no ocular involvement and 18 had unknown status. The IIOR was the first relapse in 80% of cases. Median time from PCNSL diagnosis to IIOR was 14 months (3-51). Median KPS at IIOR was 80 (70-90), the affection was symptomatic in 95%. Decreased visual acuity was the prominent symptom. 76% of the patients received systemic chemotherapy (CT): ifosfamide-based CT (25%), methotrexate-based CT (25%), temozolomide (19%), in association with rituximab in 47%. 32% received a local treatment (intraocular CT or ocular radiotherapy) alone or in association with systemic CT. 31% subsequently received high-dose CT with autologous stem cells rescue). 60% of patients relapsed subsequently (35% in the brain, 62% in the eye) with a median PFS of 10,8 months. 5-year survival rate from relapse was 53.6% (0.28-1).Conclusion: IIOR of PCNSL seem to have a better prognosis than brain relapses. That might be explained by a better KPS allowing intensification chemotherapy for up to the third of patients

Isolated intra-ocular relapses of primary central nervous system lymphoma

Abstract published in European Journal of Neurology 24(Suppl 1):52, 2017International audienceBackground and aims: Relapses in primary central nervous system lymphoma (PCNSL) are usually cerebral and severe. Isolated intraocular relapses (IIOR) are much rarer and have not been specifically studied so far.Methods: We retrospectively selected patients treated within the French national expert network on PCNSL (LOC network). The inclusion criteria were: histologically proven PCNSL with at least a cerebral localization, immunocompetent status, 1st line treatment based on high-dose methotrexate and isolated IIOR subsequently.Results: 47 patients met the inclusion criteria (median age: 64.5 years (32.8-79.7), median Karnofsky Performance Status (KPS): 70 (40-100)). Initially, 13 patients had an ocular involvement, 16 had no ocular involvement and 18 had unknown status. The IIOR was the first relapse in 80% of cases. Median time from PCNSL diagnosis to IIOR was 14 months (3-51). Median KPS at IIOR was 80 (70-90), the affection was symptomatic in 95%. Decreased visual acuity was the prominent symptom. 76% of the patients received systemic chemotherapy (CT): ifosfamide-based CT (25%), methotrexate-based CT (25%), temozolomide (19%), in association with rituximab in 47%. 32% received a local treatment (intraocular CT or ocular radiotherapy) alone or in association with systemic CT. 31% subsequently received high-dose CT with autologous stem cells rescue). 60% of patients relapsed subsequently (35% in the brain, 62% in the eye) with a median PFS of 10,8 months. 5-year survival rate from relapse was 53.6% (0.28-1).Conclusion: IIOR of PCNSL seem to have a better prognosis than brain relapses. That might be explained by a better KPS allowing intensification chemotherapy for up to the third of patients

Isolated intra-ocular relapses of primary central nervous system lymphoma

Abstract published in European Journal of Neurology 24(Suppl 1):52, 2017International audienceBackground and aims: Relapses in primary central nervous system lymphoma (PCNSL) are usually cerebral and severe. Isolated intraocular relapses (IIOR) are much rarer and have not been specifically studied so far.Methods: We retrospectively selected patients treated within the French national expert network on PCNSL (LOC network). The inclusion criteria were: histologically proven PCNSL with at least a cerebral localization, immunocompetent status, 1st line treatment based on high-dose methotrexate and isolated IIOR subsequently.Results: 47 patients met the inclusion criteria (median age: 64.5 years (32.8-79.7), median Karnofsky Performance Status (KPS): 70 (40-100)). Initially, 13 patients had an ocular involvement, 16 had no ocular involvement and 18 had unknown status. The IIOR was the first relapse in 80% of cases. Median time from PCNSL diagnosis to IIOR was 14 months (3-51). Median KPS at IIOR was 80 (70-90), the affection was symptomatic in 95%. Decreased visual acuity was the prominent symptom. 76% of the patients received systemic chemotherapy (CT): ifosfamide-based CT (25%), methotrexate-based CT (25%), temozolomide (19%), in association with rituximab in 47%. 32% received a local treatment (intraocular CT or ocular radiotherapy) alone or in association with systemic CT. 31% subsequently received high-dose CT with autologous stem cells rescue). 60% of patients relapsed subsequently (35% in the brain, 62% in the eye) with a median PFS of 10,8 months. 5-year survival rate from relapse was 53.6% (0.28-1).Conclusion: IIOR of PCNSL seem to have a better prognosis than brain relapses. That might be explained by a better KPS allowing intensification chemotherapy for up to the third of patients

Isolated intra-ocular relapses of primary central nervous system lymphoma

Abstract published in European Journal of Neurology 24(Suppl 1):52, 2017International audienceBackground and aims: Relapses in primary central nervous system lymphoma (PCNSL) are usually cerebral and severe. Isolated intraocular relapses (IIOR) are much rarer and have not been specifically studied so far.Methods: We retrospectively selected patients treated within the French national expert network on PCNSL (LOC network). The inclusion criteria were: histologically proven PCNSL with at least a cerebral localization, immunocompetent status, 1st line treatment based on high-dose methotrexate and isolated IIOR subsequently.Results: 47 patients met the inclusion criteria (median age: 64.5 years (32.8-79.7), median Karnofsky Performance Status (KPS): 70 (40-100)). Initially, 13 patients had an ocular involvement, 16 had no ocular involvement and 18 had unknown status. The IIOR was the first relapse in 80% of cases. Median time from PCNSL diagnosis to IIOR was 14 months (3-51). Median KPS at IIOR was 80 (70-90), the affection was symptomatic in 95%. Decreased visual acuity was the prominent symptom. 76% of the patients received systemic chemotherapy (CT): ifosfamide-based CT (25%), methotrexate-based CT (25%), temozolomide (19%), in association with rituximab in 47%. 32% received a local treatment (intraocular CT or ocular radiotherapy) alone or in association with systemic CT. 31% subsequently received high-dose CT with autologous stem cells rescue). 60% of patients relapsed subsequently (35% in the brain, 62% in the eye) with a median PFS of 10,8 months. 5-year survival rate from relapse was 53.6% (0.28-1).Conclusion: IIOR of PCNSL seem to have a better prognosis than brain relapses. That might be explained by a better KPS allowing intensification chemotherapy for up to the third of patients

Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL

International audiencePrognosis of Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph(+) ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. Seventy-one patients with a median age of 69 years were enrolled; 77% had a high comorbidity score. Complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. Only 7 patients underwent allogeneic hematopoietic stem cell transplantation. At 5 years, overall survival was 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24 were tested for mutation by Sanger sequencing, and 75% were T315I-positive. BCR-ABL1(T315I) was tested by allele-specific oligonucleotide reverse transcription-quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph(+) ALL. Monitoring of BCR-ABL1(T315I) from diagnosis identified patients with at high risk of early relapse and may help to personalize therap

L'ordinaire des sciences et techniques. Cultures populaires, cultures informelles (4)

International audienceLa présente édition de la Lucarne matérialise la poursuite d’un travail engagé depuis 2013. Comme pour la précédente livraison, il a été réalisé dans le cadre d’un atelier collaboratif d’histoire socioculturelle. L’atelier lui-même est animé par un collectif formé des enseignant∙e∙s et auditeur∙rice∙s des formations du CNAM dédiées à la médiation socioculturelle des sciences et techniques. Certificat de compétences, Licence professionnelle ou Magister s’attèlent ainsi à la réflexion, à la conception et à la réalisation de dispositifs pour la médiation des sciences et techniques en société par le design culturel. C’est dans ce cadre de réalisation pédagogique que sont rassemblés ces textes et documents pour lesquels sont proposés de courtes analyses sur leur fonction de support de diffusion massive dans l’espace public d’une culture populaire et ordinaire des sciences et techniques. Tous ont été rédigés dans le cadre d’un exercice exigé pour la validation d’un enseignement. Si le résultat final peut s’avérer inégalement satisfaisant à l’aune des critères de leurs commanditaires, tous les textes apportent cependant un regard jugé pertinent sur un des aspects des manifestations des sciences et techniques dans leurs rapports à la société au travers de la production et de la consommation culturelle de masse. Quelques-uns ont été un peu remaniés pour la présente édition. Retrouvez-les tous, ainsi que d’autres non publiés dans ce volume, sur le site de la Lucarne : http://ateliercst.hypotheses.org