
UN Atomic Boss Achieves Gender Parity. Just Don't Call It DEI
The head of the United Nations atomic watchdog distanced himself from policies promoting diversity, equality and inclusion in the workplace even as he sought to promote the agency's successful efforts in hiring more women.
Rafael Mariano Grossi, a top candidate to become the UN's next secretary general, achieved gender parity at the Vienna-based International Atomic Energy Agency in record time, adding hundreds of female scientists and technicians to the payroll over the last five years. Women now slightly outnumber men for the first time at the agency, best known for monitoring nuclear activities in global trouble-spots, ranging from Iran to Ukraine.
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The CANFIRE trial enrolled 11 patients treated for 6 months, while LUCAS included 36 patients treated for 4 months. Both studies failed to meet their primary endpoint, hematologic improvement in erythroid cells per International Working Group (IWG) 2018 criteria, by the end of the treatment period. Despite this, Kubasch noted that several patients opted to continue treatment due to perceived clinical benefit, such as reduced fatigue or general improvement. Some also showed biomarker changes or delayed hematologic responses. These findings led her to question whether hematologic improvement in erythroid cells is the most appropriate efficacy endpoint for immunomodulatory agents. 'We can argue that current IWG endpoint criteria are too rigid for immune modulation trials,' she said. 'Late or gradual responses may go undetected.' Kubasch suggested that future trials should incorporate patient-reported outcomes and quality-of-life metrics as co-primary endpoints. 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She proposed a stepwise stratification approach: Baseline assessment (low-risk MDS diagnosis, anemia, transfusion burden) Genetic stratification (cytogenetics, mutations, resistance markers) Immune transcriptomic profiling (HIC/MIC clustering) 'Selective inclusion of patients with immune activation, such as those with an HIC profile, is essential,' she concluded. Targeting the Right Immune Alterations Valeria Santini, MD, associate professor of hematology at the University of Florence Medical School, Italy, focused her remarks on immunosuppressive therapy, a long-used but inconsistently effective strategy in MDS. To re-evaluate its role, Santini reviewed older literature — what she called 'archaeological digging.' She showed that complete responses and survival benefits are achievable in some patients, albeit rarely. Importantly, she emphasized that immune dysfunction in MDS is dynamic. 'It changes during the course of the disease,' she said. Therefore, precise immune profiling at both the subtype and patient level is needed. Optimization of immunosuppressive therapy is hampered by the lack of prospective randomized trials, heterogeneity in study populations, poor characterization of immune abnormalities, and the need for integration with novel agents. 'It is not one cure for all,' she said. 'By selecting patients, we might be more successful than in the past.' Finding the Right Drugs and the Right Timing Lionel Adès, MD, PhD, professor of hematology at Saint-Louis Hospital, Paris, France, commented to Medscape Medical News that, while the biological rationale for immune modulation is strong, clinical evidence remains weak. Lionel Adès, MD, PhD 'Maybe we don't have the right drugs or combinations. Maybe we're using them too late in the disease course,' he said. Immune dysregulation might play a role early in MDS, but by the time patients are treated, it could be too late to alter the disease with immune-targeted agents. Moreover, Adès noted that immune therapies often require extended treatment periods before activity can be detected, while traditional MDS trial endpoints focus on earlier timepoints. 'If a drug appears completely ineffective, it's not ethical to keep a patient on trial for a year just to see if something happens,' he said. Still, he remains cautiously optimistic. He pointed to the EHA-sponsored i4MDS Consortium, which aims to deepen understanding of MDS immunobiology, and to data from the STIMULUS MDS 2 study presented during the session by Amer Zeidan, MBBS, MHS, of Yale University, New Haven, Connecticut. That study evaluated the TIM-3 immune checkpoint inhibitor sabatolimab plus azacitidine as a first-line therapy in MDS. Although the trial failed to show a survival advantage overall, subgroup analysis revealed a benefit among female patients. 'This is something very interesting,' Adès said. 'It's something we didn't look at before, because we never thought survival could differ between male and female MDS patients.' While sabatolimab development has since been discontinued, other agents targeting the same pathway remain in the pipeline. 'This finding could be valuable for stratifying future trials by sex,' he said. Kubasch reported relationships with BMS, Curis, Jazz, Johnson & Johnson, and Novartis. Santini reported serving on advisory boards for AbbVie, Ascentage, BMS, Geron, GSK, Keros, Novartis, Servier, and Takeda. Adès disclosed research support from BMS/Celgene and AbbVie, and advisory roles with AbbVie, Amgen, BMS, Jazz, Novartis, Roche, and Takeda.