Cilta-cel is a CAR-T cell therapy that expresses 2 BCMA-targeting single-domain antibodies, designed to confer avidity. In the multicohort, phase 2 CARTITUDE-2 study (NCT04133636), the safety and ...efficacy of cilta-cel in various clinical settings and suitability of outpatient administration was explored in patients with multiple myeloma.
Patients enrolled in Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and were naïve to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75 × 106 CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 for 3 days). The primary outcome was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates (per IMWG criteria) and safety (per CTCAE; CRS and ICANS by ASTCT).
As of the February 2021 data cutoff (median follow-up: 5.8 months 2.5–9.8), 20 patients (65% male; median age 60 years 38–75) received cilta-cel; 1 patient was treated in an outpatient setting. Patients (n = 12: <3 prior LOT; n = 8: 3 prior LOT) received a median of 2 (1–3) prior LOT. All patients were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to the last LOT; 40% were triple-class refractory. Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved stringent CR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. Median time to first response was 1.0 month (0.7–3.3); median time to best response was 1.9 month (0.9–5.1). Median duration of response was not reached. All patients (n = 4) with MRD-evaluable samples at 10-5 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%; grade 3/4: 90%), thrombocytopenia (80%; grade 3/4: 35%), anemia (65%; grade 3/4: 40%), lymphopenia (60%; grade 3/4: 55%), and leukopenia (55%; all grade 3/4). 85% of patients had CRS; 10% were grade 3/4. Median time to CRS onset was 7 days (5–9), with a median duration of 3.5 days (2–11). CAR-T cell neurotoxicity occurred in 20% of patients (all grade 1/2). Three patients had ICANS (n = 1: grade 1; n = 2: grade 2); median time to onset was 8 days (7–11) and median duration was 2 days (1–2). One patient had grade 2 facial paralysis; time to onset was 29 days with a duration of 51 days. One death occurred due to Covid-19 (assessed as treatment-related by investigator). The safety profile was manageable in the patient who was treated in an outpatient setting.
Updated efficacy and safety findings will inform suitability of outpatient treatment in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study.
A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in patients with MM who had 1–3 prior LOT.
Summary
Carfilzomib has been established in previous years as a treatment for patients with relapsed and/or refractory multiple myeloma (RR‐MM). A retrospective multicentre study to evaluate the ...clinical use of carfilzomib for RR‐MM outside of a clinical trial setting was conducted by our group. One hundred and thirty‐five patients were included. All patients had been previously exposed to bortezomib and 93% had also been treated with lenalidomide. The vast majority of patients received carfilzomib as part of a two‐ or three‐drug combination. The overall response rate was 47·2%. Multivariate analysis revealed bortezomib resistance, lenalidomide resistance and albumin <35 g/l to negatively impact the likelihood of achieving response. The median duration of response was 8·4 months, and was significantly higher in patients receiving three‐drug combination and patients presenting without extramedullary disease. The median progression‐free survival and overall survival for the entire cohort was 4·9 months (95% confidence interval CI 3·8–6·4) and 12·2 months (95% CI 9‐not reached), respectively. Toxicity was manageable, although treatment‐related death was seen in 5% of patients. In the setting of progressive multiple myeloma, carfilzomib in a combination regimens yields effective results with a manageable toxicity.
Hemato-oncology patients are at high risk for morbidity and mortality from coronavirus disease (COVID-19). The resultant heightened anxiety among these patients may negatively affect adherence to ...therapy and treatment-related outcome. We aimed to assess whether the adoption of precautionary measures provided by the medical team led to a reduction in COVID-19-related anxiety and, consequently, to successful execution of treatment plans.
All adult hemato-oncology patients actively treated or being followed-up at the outpatient service at Tel Aviv Sourasky Medical Center between March 25 and May 3, 2020, were invited to answer a questionnaire that focused on their anxiety and adherence to treatment following new measures to reduce risk of infection during the first COVID-19 outbreak.
One hundred and fifty patients (representing 24% of those being approached), average age 67 years, 52% male, and 57% undergoing antineoplastic therapy, responded to the survey. The introduction of precautionary measures resulted in a significant reduction in anxiety level in all patients, irrespective of age, sex, or treatment status. Attendance to scheduled visits in day care and outpatient clinics remained unchanged. Adherence to planned blood and imaging tests were 81% and 73%, respectively, and 93% of the patients were satisfied with their medical care. Thirty-two percent of patients used telemedicine. Satisfaction with telemedicine was highest among non-actively treated patients and those experiencing high anxiety levels.
Reorganization of the hemato-oncology unit and provision of information to patients reduced COVID-19-related anxiety and enabled the same delivery of therapy as that prior to the pandemic.
No firm data are available on the natural history of idiopathic thrombocytopenic purpura (ITP) or on mortality rates or frequency of major bleeding episodes associated with this condition. The ...disease is thought to have a relatively benign course, despite the frequent occurrence of very low platelet counts. This prevailing conception often guides therapeutic decisions.
To estimate the bleeding risk of ITP involving persistent low platelet counts (<30 x 10(9)/L) and its impact on prognosis.
Age-adjusted bleeding risk was derived from a pooled analysis of ITP clinical series based on a systematic literature search. The risk estimate was incorporated into a Markov model to determine its impact on prognosis.
Seventeen case series complied with inclusion criteria, including 1,817 patients with ITP. There were 49 cases of fatal hemorrhage over an estimated 1,258 to 3,023 patient-years at risk. The rate of fatal hemorrhage before age adjustment was estimated at between 0.0162 and 0.0389 cases per patient-year. Age-adjusted rates were 0.004, 0.012, and 0.130 cases per patient-year for age groups younger than 40, 40 to 60, and older than 60 years, respectively. Predicted 5-year mortality rates ranged from 2.2% for patients younger than 40 years to 47.8% for those older than 60 years. A 30-year-old woman remaining thrombocytopenic due to ITP was predicted to lose 20.4 years (14.9 quality-adjusted life years) of her potential life expectancy. At age 70, predicted loss was 9.4 years (5.0 quality-adjusted life years).
Idiopathic thrombocytopenic purpura with persistent low platelet counts carries a grave prognosis. Therefore, an active therapeutic approach in the clinical management of affected patients should be considered. In view of the significant potential implications of the model results, we call for initiating a well-designed prospective inception cohort study of patients with ITP.
Osteoporosis is a chronic condition requiring long-term treatment, for which compliance is not easy to achieve. 70 mg of alendronate once weekly (alendronate OW) provides equivalent efficacy to ...treatment with 10 mg of alendronate once a day (alendronate OD); however, there are relatively few data regarding patient and physician preferences for once-weekly vs daily dosing. The aim of this study was to measure compliance, convenience, tolerance and relative preference of alendronate OW treatment among post-menopausal women with osteoporosis and physician satisfaction, compared with previous treatment with alendronate OD.
This open-label, prospective multi-center trial was conducted at 14 hospitals and 150 primary-care community clinics in Israel. Post-menopausal osteoporotic women (n = 3710), who had been treated for at least 1 month with alendronate OD during the preceding year, were treated with alendronate OW for 12 weeks. Convenience, satisfaction, tolerance and relative preference of alendronate OW during the trial, compared with past experience with alendronate OD, were recorded.
Overall, 96% of the patients preferred the alendronate OW regimen to the 10-mg daily dosage. Nearly all (98%) the patients who completed 12 weeks of treatment, including 77% of patients who had previously discontinued daily treatment due to intolerance, were willing to continue the alendronate OW regimen. Patient-reported compliance with dosing instructions was over 98%. Alendronate OW was well tolerated; only 2.8% of patients discontinued, due to adverse events. Physicians were highly satisfied with the once-weekly dosing regimen, and recommended continued treatment with alendronate OW for 99% of the patients.
The majority of post-menopausal women with osteoporosis, including those who were previously intolerant to alendronate OD, preferred alendronate OW to the once-daily dosing regimen. It is important to consider patient preference when selecting the appropriate treatment for osteoporosis.
Predictive models have been used to identify factors that may prolong hospital length of stay (LOS). However, because predictors of LOS are collinear, the proportion of variance associated with each ...factor in a multivariate stepwise regression model may not reflect its mathematical contribution in explaining LOS. In an attempt to model factor contribution to LOS more realistically, we evaluated a clinically based clustered model. This model uses classes of candidate predictors, that is, patient attributes, adverse events, treatment modality, and health provider identity. Clusters of variables are permitted to enter into the model in a theoretically based predetermined sequence, so that the additional contribution of each cluster of factors can be assessed while the contribution of preceding factors is preserved. The clustered model was tested and compared with a free stepwise multivariate analysis in a cohort of patients undergoing prostatectomy for benign prostatic hypertrophy. We found that both models explained a similar proportion of the variance in LOS (56%–57%). However, some important differences were evident. Prostate size, associated with 12% of the variance in the clustered model, was not an independent predictor in the free model. A higher proportion of variance was associated with process variables, such as treatment modality in the free model. We conclude that use of a clustered model may facilitate more realistic assessment of the relative contribution of factors to LOS.
The impact of prostatectomy on quality of life was assessed in patients with benign prostatic hypertrophy (BPH) who were classified according to the expected benefit from surgical intervention. The ...relative impact of the 2 surgical techniques (open versus closed) on short-term quality of life was compared.
An observational study was done on 545 consecutive patients with BPH undergoing prostatectomy at 3 medical centers in Israel between 1991 and 1992. Repeated structured interviews preoperatively, and at 4 and 12 months postoperatively were performed, including 6 quality of life questionnaires evaluating BPH specific (symptom severity and symptom effect) and generic (activity, independence, mental health and health perception) parameters. In addition, the interviews consisted of socio-demographic data elements. Clinical details regarding severity of prostatic disease and co-morbidity were obtained from the medical charts.
We found a correlation between postoperative change in symptom effect and in generic quality of life measures (r-0.11 to 0.20, p less than 0.04). The postoperative decrease in the mean symptom effect score was 56 percent and 52 percent for severe and moderate preoperative levels, respectively. There was no decrease in the mean symptom effect score for the mild preoperative level (18 percent of these patients had postoperative deterioration). A secondary operation, and the combination of diabetes mellitus and poor activity level were risk factors for lack of improvement in patients with moderate preoperative symptom effects. We found that the impact of open prostatectomy on quality of life was similar to that of the closed technique after adjustment for patient attributes, except for those with an indwelling urinary catheter in whom an open operation was advantageous.
In patients with BPH and mild symptom effects, and in subgroups of patients with moderate symptom effects surgery should not be recommended. Based on short-term measures of quality of life there is no justification for a preference between open and closed operations.
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