Study identifies molecular basis of resistance to one of the main treatments for multiple myeloma CNIO_Cancer
Larissa Haertle and Santiago Barrio, from the H12O-CNIO Hematological Tumor Clinical Research Unit, have just identified one of these mechanisms in a collaborative work with the Würzburg University Hospital . They published their findings in the journalThe proteasome is the component of the cellular machinery responsible for eliminating malfunctioning proteins, the cell's equivalent of a garbage can.
Indeed, the analysis of methylation in proteasome gene sequences has evidenced more methylation in the region that controls the initiation of transcription of a particular gene, called PSMD5.
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Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosisBackground To compare the effectiveness and treatment persistence of ocrelizumab, cladribine and natalizumab in patients with relapsing–remitting multiple sclerosis switching from fingolimod. Methods Using data from MSBase registry, this multicentre cohort study included subjects who had used fingolimod for ≥6 months and then switched to ocrelizumab, cladribine or natalizumab within 3 months after fingolimod discontinuation. We analysed relapse and disability outcomes after balancing covariates using an inverse-probability-treatment-weighting method. Propensity scores for the three treatments were obtained using multinomial-logistic regression. Due to the smaller number of cladribine users, comparisons of disability outcomes were limited to natalizumab and ocrelizumab. Results Overall, 1045 patients switched to ocrelizumab (n=445), cladribine (n=76) or natalizumab (n=524) after fingolimod. The annualised relapse rate (ARR) for ocrelizumab was 0.07, natalizumab 0.11 and cladribine 0.25. Compared with natalizumab, the ARR ratio (95% confidence interval [CI]) was 0.67 (0.47 to 0.96) for ocrelizumab and 2.31 (1.30 to 4.10) for cladribine; the hazard ratio (95% CI) for time to first relapse was 0.57 (0.40 to 0.83) for ocrelizumab and 1.18 (0.47 to 2.93) for cladribine. Ocrelizumab users had an 89% lower discontinuation rate (95% CI, 0.07 to 0.20) than natalizumab, but also a 51% lower probability of confirmed disability improvement (95% CI, 0.32 to 0.73). There was no difference in disability accumulation. Conclusion After fingolimod cessation, ocrelizumab and natalizumab were more effective in reducing relapses than cladribine. Due to the low ARRs in all three treatment groups, additional observation time is required to determine if statistical difference in ARRs results in long-term disability differences. Data are available upon reasonable request. In principle, patient-level data sharing is possible. However, permission from each contributing data controller is requi
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