[Nurturing and growing a community of department heads: Act 2 in haematology]. / Faire vivre et grandir une communauté de chefs de service : acte 2 en hématologie.

In response to the French hospital system crisis and the challenges faced by the heads of departments, we have undertaken an initiative to create a community of heads of haematology departments willing to assist each other. Our inaugural seminar, held in January 2023, established the foundational "core" group of heads of department. Throughout 2023, this emerging community has prospered, offering sustained support to peers. In January 2024, we broadened our community to include other heads of departments, following a second seminar gathering 36 participants. During this event, we took the time to exchange thoughts and reflect on our missions. Building on the experience of guest speakers and employing methods of co-development and co-construction in plenary sessions, small-group workshops, and social gathering, we were able to discover and experience the collective intelligence, creativity, strength, and support stemming from such a group. This peer community of heads of departments stands as a powerful tool for management support, whereby personal experiences nourish and enrich the experience of others. We hope that our initiative will inspire heads of departments from other specialties so that, together, we can better work towards our missions as heads of departments and collaborate on rebuilding the hospital "from the bottom up".

Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma in real-world: The retrospective IMAGE study.

BACKGROUND: IMAGE is a retrospective cohort study of patients enrolled in early access programs (EAPs) in France with relapsed/refractory multiple myeloma (RRMM) receiving isatuximab with pomalidomide and dexamethasone (Isa-Pd). METHODS: Patients aged ≥18 years with RRMM who received ≥1 dose of Isa under the EAPs between July 29, 2019 and August 30, 2020 were included. Effectiveness endpoints included progression-free survival (PFS) and response rates. Verbatim terms for adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities and not graded for severity. RESULTS: A total of 294 and 299 patients were included in the effectiveness and safety populations, respectively. IMAGE included patients who received one prior line of treatment (10.2%) and were daratumumab-refractory (19.1%). At median follow-up of 14.2 months, median PFS in the effectiveness population was 12.4 months (95% CI 9.0-15.0). Overall response and very good partial response rates were 46.3% and 27.9%, respectively. Subgroup analyses reflected similar results. In the safety population, 26.4% of patients reported at least one AE; the most common any-grade AE was neutropenia (9.4%). CONCLUSION: IMAGE demonstrated Isa-Pd had meaningful effectiveness in median PFS and depth of response and no new safety signals in a real-world context, consistent with clinical trial results.

Real-life effectiveness of carfilzomib in patients with relapsed multiple myeloma receiving treatment in the context of early access: The CARMYN study.

The real-life retrospective observational study CARMYN aimed at investigating the long-term efficacy and safety of carfilzomib in combination with dexamethasone and lenalidomide (KRd, 159 patients). These patients (62% in first and 38% in second relapse, median age 62 yo) were treated between 02/2014 and 02/2017. Most had been pre-exposed to bortezomib (98.2%) and to an IMID (75.4%). At the time of collection, 90% had permanently discontinued carfilzomib. Data collection was conducted from January to July 2021 in 27 participating sites, after a median of 39 months follow-up. For patients treated with KRd, an overall response rate of 78.4% translated in a median progression free survival (PFS) of 24.0 months (95% CI 18.8-27.6) and a median overall survival (OS) of 51.1 months (95% CI 41.3-not reached). Results were poorer but difficult to interpret in the small cohort of Kd recipients. The study is one of the longest real-life studies of carfilzomib treatment in patients in first or second relapse. CARMYN confirmed the real-life long-term efficacy of carfilzomib in combination with lenalidomide and dexamethasone with results similar to those of clinical trials. The KRd regimen is thus an option to consider for late relapses in the current context of MM management.

Autologous stem-cell collection following VTD or VRD induction therapy in multiple myeloma: a single-center experience.

Triplet-drug regimen bortezomib-thalidomide-dexamethasone (VTD) and bortezomib-lenalidomide-dexamethasone (VRD) are considered as standard of care induction prior autologous stem-cell transplantation (ASCT) in myeloma. In addition to improve response rate, induction therapy should preserve an adequate stem-cell collection. In the present retrospective study, we analyzed stem-cell collection in 325 newly diagnosed myeloma patients who received either VTD or VRD induction before ASCT. Stem-cell mobilization consisted of intravenous cyclophosphamide plus G-CSF. Plerixafor was administered preemptively to rescue mobilization. In comparison with VTD, VRD induction was associated with a more frequent use of plerixafor (19.3% versus 5.4%, p = 0.004) and with an increased number of apheresis to reach adequate collection (>2 apheresis required in 42.3% versus 30.2%, p = 0.05). Moreover, more patients experienced collection failure in the VRD group (6% versus 1.8%, p = 0.004). The median number of CD34-positive cells (×106/kg) was lower in the VRD group: 8.5 versus 9.3 (p = 0.05) in the VTD group. The vast majority of patients underwent ASCT (93% versus 98%, in VRD and VTD group, respectively). These data highlight the need of optimal stem-cell collection strategy, especially in the context of tandem transplantation and incorporation of anti-CD38 monoclonal antibody into induction.

Diagnosis and prognosis are supported by integrated assessment of next-generation sequencing in chronic myeloid malignancies. A real-life study.

Next-generation sequencing (NGS) is used to investigate the presence of somatic mutations. The utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains unclear. We report the findings of an observational, multicenter study that aimed to assess the impact of somatic mutation testing by NGS in a reallife setting of chronic myeloid malignancies. A total of 177 patients were enrolled, partitioned into two overlapping groups. In group A (n=94), the indication was to search for clonal hematopoiesis, in a context of suspected myelodysplastic syndrome or myeloproliferative neoplasia. In group B (n=95), the theranostic impact of somatic mutations was studied. A panel of 34 genes was used on DNA extracted from blood or bone marrow samples. Within group A, the detection of clonal hematopoiesis supported the diagnosis of chronic myeloid malignancies for 31 patients while the absence of clonal hematopoiesis ruled out the suspected diagnosis in 47 patients. Within group B, NGS identified prognostically relevant somatic mutations in 32 patients, which had a therapeutic impact in 18 cases. By determining the presence or absence of somatic mutations, the application of NGS in daily practice was found to be useful for an integrated final diagnosis in 83% of the patients. Moreover, the search for somatic mutations had a prognostic impact that led to treatment modification in 19% of the cases. This study outlines the fact that adequate implementation of new investigations may have a significant positive medico-economic impact by enabling appropriate management of patients.