French early nationwide idecabtagene vicleucel chimeric antigen receptor T-cell therapy experience in patients with relapsed/refractory multiple myeloma (FENIX): A real-world IFM study from the DESCAR-T registry.

Idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real-world registry-based multicentre observational study in 11 French hospitals to evaluate ide-cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR-T registry. Of these, 159 patients (90%) received ide-cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression-free survival (PFS) from the ide-cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra-medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA-targeted immunoconjugate or T-cell-redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide-cel's feasibility, safety and efficacy in real-life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection.

Real-world effectiveness of ixazomib combined with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: the REMIX study.

Ixazomib (IXA) is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone (IXA-Rd) for patients with relapsed and/or refractory multiple myeloma (RRMM). The REMIX study is one of the largest prospective, real-world analysis of the effectiveness of IXA-Rd in the setting of RRMM. Conducted in France between August 2017 and October 2019, the REMIX study, a non-interventional prospective study, included 376 patients receiving IXA-Rd in second line or later and followed for at least 24 months. Primary endpoint was the median progression-free survival (mPFS). Median age was 71 years (Q1-Q3 65.0 - 77.5) with 18.4% of participants older than 80 years. IXA-Rd was initiated in L2, L3 and L4 + for 60.4%, 18.1% and 21.5%, respectively. mPFS was 19.1 months (95% CI [15.9, 21.5]) and overall response rate (ORR) was 73.1%. mPFS was 21.5, 21.9 and 5.8 months in patients receiving IXA-Rd as L2, L3, L4 + respectively. Among patients receiving IXA-Rd in L2 and L3, mPFS was similar for patients previously exposed to lenalidomide (19.5 months) than for those lenalidomide naive (not exposed, 22.6 months, p = 0.29). mPFS was 19.1 months in patients younger than 80 years and 17.4 months in those 80 years or older (p = 0.06) with similar ORR (72.4% and 76.8%) in both subgroups. Adverse events (AEs) were reported in 78.2% of patients including 40.7% of treatment-related AE. IXA discontinuation was due to toxicity in 21% of patients. To conclude, the results of the REMIX study are consistent with the results of Tourmaline-MM1 and confirm the benefit of IXA-Rd combination in real life. It shows the interest of IXA-Rd in an older and frailer population, with an acceptable effectiveness and tolerance.

Thromboembolic events and thromboprophylaxis associated with immunomodulators in multiple myeloma patients: a real-life study.

PURPOSE: The aim of this study is to assess international guidelines implementation concerning thromboprophylaxis strategy in myeloma patients treated with immunomodulatory drugs. METHODS: This retrospective study includes multiple myeloma patients treated with immunomodulatory drugs between 2014 and 2017 in the Hematology department of a teaching hospital (Hospices Civils de Lyon, France) and followed by the multidisciplinary care plan for cancer outpatients ONCORAL (ONCological care for outpatients with ORAL anticancer drugs). Data from immunomodulatory drugs administration, thromboprophylaxis strategy and thrombotic events were collected from medical files. Adherence to 2010 International Myeloma Working Group (IMWG) guidelines was assessed. RESULTS: 213 patients received at least one immunomodulatory drug: lenalidomide (60.9%), pomalidomide (24.0%) and thalidomide (15.1%). About two third of treatment lines (66.2%) were in accordance with IMWG recommendations. Among the others, 30.5% and 69.5% had thromboprophylaxis, respectively, superior or inferior to IMWG recommendations. 37 venous thrombotic events and 4 arterial thromboembolisms (one patient experienced both a stroke and deep venous thrombosis simultaneously) were reported. CONCLUSION: Thromboprophylaxis was systematically performed in myeloma patients treated with immunomodulatory drugs in this real-life retrospective cohort. However, the choice of anticoagulant or anti-platelet agent remains debatable, as adherence to existing guidelines was variable.

Survey to describe variability in early onset scoliosis cast practices.

PURPOSE: To investigate paediatric orthopaedists' cast practices for early onset scoliosis regarding patient selection, cast application, radiographic evaluation, treatment cessation and adjunctive bracing. METHODS: A casting survey was distributed to all paediatric orthopaedists in Children's Spine and Growing Spine Study Groups (n = 92). Questions included physician and patient characteristics, technique, treatment, outcomes, radiographic measurements and comparison to other treatments. A total of 55 orthopaedists (60%) responded, and descriptive statistics were calculated on the subset who cast (n = 45). RESULTS: A majority of respondents use cast treatment for idiopathic and syndromic scoliosis patients, but not for neuromuscular or congenital scoliosis patients. Major curve angle ranked most important in orthopaedists' decision to commence cast treatment, in comparison with rib-vertebra angle difference or clinical observations. The major curve angle threshold to initiate casting was a median of 30° (20° to 70°), and the minimum patient age was median ten months (3 to 24). First in-cast and out-of-cast radiographs are taken standing, supine, awake, under anesthesia and/or in traction. In all, 58% consistently cast over or under the arm, while 44% vary position by patient. Respondents were divided about the use of a brace after cast treatment: 22% do not prescribe a brace, 31% always do and 36% do in some patients. CONCLUSIONS: Future multicentre research studies must standardize radiographic practices and consider age and major curve angle at cast initiation and termination, scoliosis aetiology, shoulder position and treatment duration. Practices need to be aligned or compared in these areas in order to distinguish what makes for the best cast treatment possible.Level of Evidence: V, Expert opinion.

Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma.

BACKGROUND: The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression-free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. DESIGN: We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (≥1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies. We then analyzed the characteristics of patients according to duration of treatment. RESULTS: The overall response rate (ORR) for the <1-year group was 43%, the median PFS 4.6 months [95% confidence interval (95% CI) 3.8-6.4] with only 6% at 12 months, and the median OS was 15 months (11.7-20.3) and 40% at 18 months. For the ≥1-year group, the response rate and survival were strikingly different, ORR at 83%, median PFS 20.7 months (14.7-35.4), median OS not reached, and 91% at 18 months. CONCLUSION: Pomalidomide and dexamethasone favored prolonged and safe exposure to treatment in 40% of heavily treated and end-stage RRMM, a paradigm shift in the natural history of RRMM characterized with a succession of shorter disease-free intervals and ultimately shorter survival. Although an optimization of pomalidomide-dexamethasone regimen is warranted in advanced RRMM, we claim that pomalidomide has proven once more to change the natural history of myeloma in this series, which should be confirmed in a larger study.

[Pomalidomide for multiple myeloma]. / Le pomalidomide dans le myélome multiple.

Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of "novel agents": proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority - if not all - of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This review focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.

Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients.

Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there is a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myélome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for progression-free survival (PFS): 1p22: 19.8 months vs 33.6 months (P<0.001) and 1p32: 14.4 months vs 33.6 months (P<0.001); and overall survival (OS): 1p22: 44.2 months vs 96.8 months (P=0.002) and 1p32: 26.7 months vs 96.8 months (P<0.001). In multivariate analyses, 1p22 and 1p32 deletions still appear as independent negative prognostic factors for PFS and OS. In conclusion, our data show that 1p22 and 1p32 deletions are major negative prognostic factors for PFS and OS for patients with MM. We thus suggest that 1p32 deletion should be tested for all patients at diagnosis.

[Petrous plasmacytoma revealed by a painful peripheral facial palsy]. / Plasmocytome du rocher révélé par une paralysie faciale périphérique douloureuse.

INTRODUCTION: The classical hypothesis of Bell's palsy, tempting in cases of peripheral facial palsy of rapid onset, must nevertheless be evoked with caution particularly if an intense pain is present, which should lead to search for a tumor of the skull base, especially the petrous bone. CASE REPORT: A 43-year-old man presented a peripheral facial palsy of rapidly progressive onset. A petrous bone tumor was diagnosed on the CT scan, which revealed an aspect of a glomic tumor or a metastatic lesion. The final histological diagnosis was plasmacytoma. DISCUSSION: This type of tumor has been rarely reported in this location. The radiological features are not specific at all, underlying the importance of searching for some associated signs such as a monoclonal protein and performing a histological examination when the firm diagnosis of a systemic disease like multiple myeloma has not been possible.

Tandem autologous non-myeloablative allogeneic transplantation in patients with multiple myeloma relapsing after a first high dose therapy.

We retrospectively studied a series of 23 patients (median age 50 years, range 29-59 years) with multiple myeloma (MM), treated in first relapse by a sequential autologous-allogeneic tandem approach. Tandem transplantation (TT) consisted in high dose melphalan (HDT) and auto-SCT followed by an (allo-SCT) preceded by two gray TBI non-myeloablative conditioning. All patients received a first HDT as frontline treatment. At day 100 post allo-SCT, complete donor chimerism was detected in 22 patients (95%). Acute GVHD was observed in 19 patients (15 grade I-II (65%) and 4 grade III-IV (17%)). Ten patients (43%) developed an extensive chronic GVHD. The non-relapse mortality at 1 year was 17%. After TT, the overall response rate was 91% (17% partial response, 35% very good partial remission and 39% complete remission). At 2 years, OS was 61%. Median event-free survival and OS were 36.8 and 60 months, respectively. Based on the propensity score matching method, a significant survival advantage could be seen in patients treated with TT as compared with non-allografted patients. Thus, allo-SCT, in TT approach, provides a high response rate with low toxicity and may improve survival of patients with relapsing MM.

Respiratory status deterioration during G-CSF-induced neutropenia recovery.

Exacerbation of prior pulmonary involvement may occur during neutropenia recovery. Granulocyte colony-stimulating factor (G-CSF)-related pulmonary toxicity has been documented in cancer patients, and experimental models suggest a role for G-CSF in acute lung injury during neutropenia recovery. We reviewed 20 cases of noncardiac acute respiratory failure during G-CSF-induced neutropenia recovery. Half the patients had received hematopoietic stem cell transplants. All patients experienced pulmonary infiltrates during neutropenia followed by respiratory status deterioration coinciding with neutropenia recovery. Neutropenia duration was 10 (4-22) days, and time between respiratory symptoms and the first day with more than 1000 leukocytes/mm3 was 1 (-0.5 to 2) day. Of the 20 patients, 16 received invasive or noninvasive mechanical ventilation, including 14 patients with acute respiratory distress syndrome (ARDS). Five patients died, with refractory ARDS. In patients with pulmonary infiltrates during neutropenia, G-CSF-induced neutropenia recovery carries a risk of respiratory status deterioration with acute lung injury or ARDS. Clinicians must maintain a high index of suspicion for this diagnosis, which requires eliminating another cause of acute respiratory failure, G-CSF discontinuation and ICU transfer for early supportive management including diagnostic confirmation and noninvasive mechanical ventilation.

Midodrine for the management of orthostatic hypotension in patients with spinal cord injury: A case report.

A 21-year-old man sustained anterior displacement and a burst fracture of C7 in a motor vehicle crash. He underwent anterior corpectomy, decompression, fusion of C6-T1 vertebrae, and halo placement. The American Spinal Injury Association grade of his spinal cord injury (SCI) was C6 C tetraplegia. Severe orthostatic hypotension in the upright position complicated the patient's rehabilitation program. Midodrine was prescribed, and other medications with possible adverse effects were adjusted. Significant improvement after taking midodrine was reflected in the orthostatic vital signs and symptoms, as well as in FIM instrument scores. Staff noted improvements with therapy participation and functional status. The patient tolerated the midodrine well and had no significant side effects.

Transoesophageal echocardiography during scoliosis repair: comparison with CVP monitoring.

PURPOSE: Accurate haemodynamic assessment during surgical repair of scoliosis is crucial to the care of the patient. The purpose of this study was to compare transoesophageal echocardiography (TEE) with central venous pressure monitoring in patients with spinal deformities requiring surgery in the prone position. METHODS: Twelve paediatric patients undergoing corrective spinal surgery for scoliosis/kyphosis in the prone position were studied. Monitoring included TEE, intra-arterial and central venous pressure monitoring (CVP). Haemodynamic assessment was performed prior to and immediately after positioning the patient prone on the Relton-Hall table. Data consisted of mean arterial blood pressure (mBP), heart rate (HR), CVP, left ventricular end-systolic and end-diastolic diameters (LVESD and LVEDD respectively) and fractional shortening (FS). Right ventricular (RV) function and tricuspid regurgitation (TR) were assessed qualitatively. Analysis was performed using descriptive statistics, Student's t test, sign rank, and correlation analysis. RESULTS: There was an increase in CVP (8.7 mmHg to 17.7 mmHg; P < .01), and decreases in LVEDD (37.1 mm to 33.2 mm; P < .05), and mean blood pressure (75.0 mmHg to 65.7 mmHg; P < .05) when patients were placed in the prone position. Fractional shortening, LVESD, and HR did not change from the supine to the prone position. Right ventricular systolic function and tricuspid regurgitation were unchanged. CONCLUSION: These data indicate that the CVP is a misleading monitor of cardiac volume in patients with kyphosis/scoliosis in the prone position. This is consistent with previous studies. In this clinical situation, TEE may be a more useful monitoring tool to assess on-line ventricular size and function.

A reassessment of spinal stabilization in severe cerebral palsy.

A homogenous population of 37 institutionalized patients with scoliosis and severe cerebral palsy was evaluated to assess the impact of spinal stabilization on comfort, function, health, and ease of nursing care. Through a prospective care-burden study, a 34-month retrospective analysis, and a healthcare worker questionnaire, 17 fused patients with a mean current scoliosis of 35 degrees were compared with 20 nonfused patients with a mean scoliosis of 76 degrees. No clinically significant differences were noted in pain or pulmonary medication utilization or therapy, decubiti, function, or time for daily care. Nevertheless, the majority of healthcare workers believed that the fused patients were more comfortable.

The relationship between preoperative nutritional status and complications after an operation for scoliosis in patients who have cerebral palsy.

The records of forty-four patients who had cerebral palsy and spastic quadriplegia and in whom a spinal arthrodesis had been done for scoliosis were reviewed to determine if the preoperative nutritional status of the patients was associated with the rate of postoperative complications. The patients were divided into two groups: Group 1 consisted of twenty-four patients who had a preoperative level of serum albumin of at least thirty-five grams per liter (3.5 milligrams per cent) and a total blood-lymphocyte count of at least 1.5 grams per liter (1500 cells per cubic millimeter), and Group 2 consisted of twenty patients who had a preoperative level of serum albumin of less than thirty-five grams per liter (3.5 milligrams per cent) and a total blood-lymphocyte count of less than 1.5 grams per liter (1500 cells per cubic millimeter). The patients in Group 1 had a significantly lower rate of infection, a shorter period of endotracheal intubation after the operation, and a shorter period of hospitalization.

Advances in pediatric orthopaedics.

New technology is fueling advances in pediatric orthopaedics. Ultrasonography represents a safe and highly accurate method of screening for hip dislocation and dysplasia that is superior to the clinical examination. Image intensification now provides a safe and more anatomically accurate method for the operative treatment of slipped capital femoral epiphysis. Magnetic resonance imaging allows for greater accuracy in the diagnosis of subtle neural abnormalities associated with congenital spinal deformities. Adjuvant chemotherapy and the treatment of osteogenic sarcoma have greatly improved the survival rate and permitted the use of limb-sparing procedures in children.

Segmental spinal dysgenesis.

Segmental spinal dysgenesis is characterized by focal agenesis or dysgenesis of the lumbar or thoracolumbar spine, with focal abnormality of the underlying spinal cord and nerve roots. Children are symptomatic at birth with lower limb deformities and neurological deficits that may be segmental. Myelography and computed tomography disclose hypoplastic or absent vertebrae and atrophic or absent neural elements adjacent to the bony deformity; the spinal column distal to the abnormality may be partially bifid, but is otherwise normal. Spinal ultrasonography was a helpful diagnostic adjunct in one patient. Surgery may be helpful in decompressing partially functioning spinal cord or nerve roots, but may exaggerate the tendency toward spinal instability. The embryology of this abnormality is not clear, but two children had other anomalies suggesting a spinal dysraphic syndrome, and its cause is probably related to a segmental maldevelopment of the neural tube.