Background
Steroid-sensitive nephrotic syndrome (SSNS) is, in most patients, a chronic disease with 80% experiencing at least one relapse after first flare. B cell depletion using rituximab is effective in preventing relapse in steroid-dependent (SDNS) patients but fails to maintain long-term remission following B cell recovery, possibly due to development of autoreactive long-lived plasma cells. We investigated sequential combination of antiCD20 antibody targeting all B cell subsets, and antiCD38 antibody with high plasma cell cytotoxicity in patients with uncontrolled SDNS after failure of one or several attempts at B cell depletion.
Methods
Fourteen patients with median disease duration 7.8 years received 1000 mg/1.73 m
2
obinutuzumab followed by 1000 mg/1.73 m
2
daratumumab 2 weeks later. Oral immunosuppression was discontinued within 6 weeks, and biological monitoring performed monthly until B cell recovery.
Results
Median age at treatment was 11.0 [IQR 10.4–14.4] years. B cell depletion was achieved in all patients, and B cell reconstitution occurred in all at median 9.5 months after obinutuzumab injection. After median follow-up 20.3 months (IQR 11.5–22.6), 5/14 patients relapsed including 4 within 100 days following B cell repletion. Relapse-free survival was 60% at 24 months from obinutuzumab infusion. Mild infusion reactions were reported in 3/14 patients during obinutuzumab and 4/14 during daratumumab infusions. Mild transient neutropenia (500–1000/mm
3
) occurred in 2/14 patients. Intravenous immunoglobulins were given to 12/14 patients due to hypogammaglobulinemia. Low IgA and IgM levels were noted in 8 and 14 patients, respectively. No severe infection was reported.
Conclusion
Global antiB cell strategy combining obinutuzumab and daratumumab induces prolonged peripheral B cell depletion and remission in children with difficult-to-treat SDNS.
Electronic supplementary material
The online version of this article (10.1007/s00467-020-04811-0) contains supplementary material, which is available to authorized users.
Nous présentons dans cet article un système de mesure simultanée de la conductivité σ, et du pouvoir thermoélectrique S : il permet des mesures en fonction de la température (entre 130 K et 360 K) dans le cas de couches semi-conductrices relativement fragiles. A titre d'application, nous indiquons les résultats que nous avons obtenus dans le cas de couches polymères (PPP) implantées avec des ions sodium: alors que seule une semi-conduction par défaut est générée par de fortes énergies d'implantation (E = 250 keV ), il apparaît une semiconduction induite par le dopage n lors d'implantations à basse énergie (E = 30 keV )
Background
Neuropathic pain is common in cancer survivorship and is one of the most distressing symptoms for patients previously treated for head and neck cancer. Persistent neuropathic pain, when it is ongoing and uncontrolled, has a detrimental effect and erodes patients’ quality of life. Patients treated for head and neck cancer are chronic opioid users to manage their post-treatment pain, which may entail an increased risk of addiction and overdose. We propose to evaluate the analgesic activity of high-concentration capsaicin patches for the treatment of head and neck cancer survivors presenting with neuropathic pain sequelae.
Methods
TEC-ORL is a parallel, multicenter randomized comparative phase II study evaluating whether Capsaïcin patches (Qutenza®) reduce neuropathic pain when compared to Amitriptyline (Laroxyl®) in head and neck cancer survivors presenting with neuropathic pain sequelae. The primary efficacy outcome is the rate of patients with a pain reduction of at least two points at 9 months compared to baseline. Assuming that 5% of patients become lost to follow-up, 130 patients will need to be randomized to detect a 25% improvement (i.e., standard: 25%, experimental: 50%) using a one-sided chi-square test with an alpha of 0.05%. According to the recommendations for comparative phase II trials, the target differences and type I error rates are relaxed. Randomized patients will either be treated with a capsaicin 8% (Qutenza®) patch applied at three time intervals in the experimental arm or with Amitriptyline (Laroxyl®) (oral solution 40 mg/ml) taken for 9 months at the recommended daily dose of 25 mg to 75 mg in the control arm.
Discussion
TEC-ORL is a randomized comparative phase II trial designed to comprehensively evaluate the analgesic activity of capsaicin compared to Laroxyl in Head and Neck Cancer survivors presenting with neuropathic pain sequelae.
Trial registration
ClinicalTrials.gov identifier: NCT04704453 Date of registration: 2021/01/13.
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