Plain language summary of isatuximab plus carfilzomib, lenalidomide, and dexamethasone for the treatment of people with high-risk newly diagnosed multiple myeloma.

What is this summary about? This is a summary of a publication about the GMMG-CONCEPT study that was published in the Journal of Clinical Oncology in September 2023. The study tested if a combination of cancer drugs (isatuximab plus carfilzomib, lenalidomide, and dexamethasone, or Isa-KRd for short) was a safe treatment for people with high­risk newly diagnosed multiple myeloma. The GMMG-CONCEPT study included participants who had not been treated before and were eligible to receive a procedure called autologous stem cell transplant, as well as participants who were not eligible to receive transplants.How was the study in this summary conducted? This report looked at a total of 125 participants; 99 were transplant-eligible and 26 were transplant-non-eligible. All participants were treated with Isa-KRd. The researchers measured the proportion of people who had 'no detectable levels' of myeloma cells in their body left while on treatment (called minimal residual disease negativity, or MRD negativity for short). The researchers measured the progression-free survival, or the average length of time it took between the participants joining the study until their cancer got worse or they died. The researchers also measured overall survival, which is the total amount of time people lived during the study, even if their cancer got worse. The researchers also monitored for side effects of Isa-KRd in all participants that received at least one treatment.What were the results of the study? At the end of the consolidation therapy (intensified therapy that happens after initial therapy), MRD negativity was observed in the majority of transplant-eligible and transplant non-eligible patients. For many patients, this effect lasted 6 or more months. After more than 3 years in transplant eligible participants and 2 years and 9 months for transplant non-eligible participants, most participants were alive and their disease did not get worse. In both groups, the most common side effects of Isa-KRd treatment were low blood cell counts and infections. Overall, most of the side effects did not last long or were easily treated.What were the main conclusions reported by the researchers? In the GMMG-CONCEPT study, Isa-KRd treatment reduced the number of myeloma cells to no detectable levels in more than two thirds of the participants with high-risk newly diagnosed multiple myeloma.Clinical Trial Registration: NCT03104842 (ClinicalTrials.gov).

Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin.

Measurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITDpos) was hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)-based MRD assay with a limit of detection of 10-4 to 10-5, we evaluated the prognostic impact of MRD at different time-points in 157 FLT3-ITDpos AML patients enrolled in the AMLSG16-10 trial (NCT01477606) combining intensive chemotherapy with midostaurin followed by midostaurin maintenance. Achievement of MRD negativity (MRDneg) after two cycles of chemotherapy (Cy2) observed in 111/142 (78%) patients predicted for superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR, 26% vs 46%; P=.001) and overall survival (OS) (4y-OS, 70% vs 44%; P=.012). This survival advantage was also seen for patients undergoing allogeneic hematopoietic-cell transplantation in first complete remission (4y-CIR, 14% vs 39%; P=.001; 4y-OS, 71% vs 49%; P=.029). Multivariate models for CIR and OS after Cy2 revealed FLT3-ITD MRDneg as the only consistent favorable variable for CIR (HR, 0.29; P=.006) and OS (HR, 0.39; P=.018). NPM1 co-mutation correlated with deeper molecular response as reflected by stronger MRD reduction and higher rate of FLT3-ITD MRDneg after Cy2. During follow-up, conversion from MRDneg to MRDpos was a strong, independent factor for inferior CIR (HR, 16.64; P<.001) and OS (HR, 4.05; P<.001). NGS-based FLT3-ITD MRD monitoring allows for the identification of patients at high risk of relapse and death following intensive chemotherapy plus midostaurin. Using NGS-based technology, FLT3-ITD emerges as a novel, clinically highly relevant target for MRD monitoring.

[Gender-specific differences in bariatric surgery: epidemiology, treatment and results]. / Geschlechtsspezifische Unterschiede in der Adipositaschirurgie: Epidemiologie, Therapie und Ergebnisse.

This study investigates gender-specific differences in obesity and the treatment by metabolic bariatric surgery (MBS). The database includes 2393 patients (1725 women, 668 men) from for a high-volume center for bariatric surgery. Demographic, perioperative and follow-up data were retrospectively analyzed. Men had a significantly higher body mass index (BMI) and more frequent obesity-associated diseases. Despite the higher prevalence of obesity in men, women accounted for 80% of the surgical patients. On average men had longer operation times but with the same complication rates. Postoperatively, both sexes experienced a significant reduction in excess body weight, which was slightly more pronounced in women. The study particularly emphasizes the need to better motivate men to undergo obesity treatment in order to reduce the health consequences of morbid obesity in this population group.

Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma.

PURPOSE: The GMMG-CONCEPT trial investigated isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in transplant-eligible (TE) and transplant-noneligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) with exclusively high-risk disease for whom prospective trials are limited, aiming to induce minimal residual disease (MRD) negativity. METHODS: This academic, investigator-initiated, multicenter, phase II trial enrolled patients with high-risk NDMM (HRNDMM) defined by mandatory International Staging System stage II/III combined with del17p, t(4;14), t(14;16), or more than three 1q21 copies as high-risk cytogenetic aberrations (HRCAs). Patients received Isa-KRd induction/consolidation and Isa-KR maintenance. TE patients received high-dose melphalan. TNE patients received two additional Isa-KRd cycles postinduction. This prespecified interim analysis (IA) reports the primary end point, MRD negativity (<10-5, next-generation flow), at the end of consolidation. The secondary end point was progression-free survival (PFS). RESULTS: Among 125 patients with HRNDMM (TE-intention-to-treat [ITT]-IA, 99; TNE-ITT, 26) of the IA population for the primary end point, the median age was 58 (TE-ITT-IA) and 74 (TNE-ITT) years. Del17p was the most common HRCA (TE, 44.4%; TNE, 42.3%); about one third of evaluable TE/TNE patients presented two or more HRCAs, respectively. The trial met its primary end point with MRD negativity rates after consolidation of 67.7% (TE) and 54.2% (TNE) of patients. Eighty-one of 99 TE-ITT-IA patients reached MRD negativity at any time point (81.8%). MRD negativity was sustained for ≥1 year in 62.6% of patients. With a median follow-up of 44 (TE) and 33 (TNE) months, median PFS was not reached in either arm. CONCLUSION: Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status, translating into a median PFS that was not yet reached after 44/33 months.