Efficacy and tolerability of VCD chemotherapy in a UK real-world dataset of elderly transplant-ineligible newly diagnosed myeloma patients.

OBJECTIVE: There are limited data on the efficacy and tolerability of VCD chemotherapy in transplant-non-eligible (TNE) newly diagnosed myeloma (NDMM) patients. In this retrospective study, we set out to evaluate this triplet combination in this setting across Thames Valley Cancer Network (UK). METHODS: The primary end point was overall response rate (ORR). Secondary outcomes included event-free survival (EFS), overall survival (OS) and adverse events (AEs). RESULTS: In a total cohort of 158 patients, ORR for total cohort was 72.1%. Median EFS was 10.5 months, and for subgroups by age (<75:11.7 vs ≥75:10.3 months, P = .124), by Charlson Co-morbidity Index (CCI) (<5:11.1 vs ≥5:8.2 months, P = .345). The 4-month landmark analysis showed the following median EFS results: by cumulative bortezomib dose (≥26 mg/m2 : 9.0 months vs <26 mg/m2 : 6.4, P = .13), by cumulative cyclophosphamide dose (≥7000 mg: 9.2 vs <7000 mg: 7.0 months, P = .02) and by cumulative dexamethasone dose (>600 mg: 7.8 vs ≤600 mg: 8.3 months, P = .665). Median OS was 46.9 months. The incidence rate of AE was as follows: any grade (76.8%), ≥G3 (27.1%), ≥G3 haematological AEs (7.9%), any grade infections (31.1%) and ≥G3 infections (11.9%). CONCLUSION: This study demonstrated a good ORR achieved from fixed duration VCD, which was reasonably well tolerated. This was followed by modest median EFS. We envisage that the latter may be improved in this patient group with the use of a higher cumulative bortezomib dose (≥26 mg/m2 ) which showed a trend for improved EFS although without statistical significance (P = .13), and with the use of a higher cumulative cyclophosphamide doses (≥7000 mg, P = .02), subject to tolerability and close monitoring.

Evaluation of the frailty characteristics and clinical outcomes according to the new frailty-based outcome prediction model (Myeloma Risk Profile-MRP) in a UK real-world cohort of elderly newly diagnosed Myeloma patients.

The management of myeloma in the elderly is shifting its focus towards reducing the risk of under-treating fit patients and the risk of over-treating frail patients. Frailty assessment is required in this patient group in order to individualise treatment decisions. In addition to the proven prognostic values of the International Myeloma Working Group (IMWG) frailty score and the revised Myeloma Co-morbidity Index (R-MCI), a new easy-to-use frailty-based risk profile score (high-risk (i.e. frail), medium risk (i.e. intermediate-fitness) and low-risk (i.e. fit)) named Myeloma Risk Profile (MRP) was shown to be predictive of survival in the clinical trial setting. In this retrospective real-world study, we set out to evaluate the frailty characteristics and clinical outcomes according to the different MRP scoring algorithm categories (frail vs. intermediate vs fit), in a high risk cohort of elderly newly diagnosed myeloma patients treated with the fixed-duration triplet therapy VCD (bortezomib with cyclophosphamide and dexamethasone). Clinical outcomes included: reason for treatment discontinuation, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Out of 100 patients, 62 were frail, 27 were intermediate and 11 were fit, according to MRP scores. To enable meaningful comparisons between comparable numbers, subgroups analyses for ORR, OS, PFS, and AEs focused on frail (n = 62) versus intermediate or fit (n = 38) patients. The proportion of patients in each subgroup who were able to complete the planned course of treatment was (frail: 43.5% vs. intermediate or fit: 55.3%). A higher proportion in the frail subgroup discontinued therapy due to progressive disease (19.4% vs. 2.6%). Discontinuation due to toxicity was comparable across subgroups (14.5% vs. 15.8%), ORR in the total cohort was 75%, and this was comparable between subgroups (frail: 74.2% vs. intermediate or fit: 76.3%). There was a trend for a shorter median OS in the frail subgroup but without a statistical significance: (frail vs. intermediate or fit): (46 months vs. not reached, HR: 1.94, 95% CI 0.89-4.2, p = 0.094). There was no difference in median PFS between subgroups: (frail vs. intermediate or fit): (11.8 vs. 9.9 months, HR: 0.99, 95% CI: 0.61-1.61, P = 0.982). This cohort demonstrated a higher incidence rate of AEs in frail patients compared to those in the intermediate or fit group: patients with at least one any grade toxicity (85.5% vs. 71.1%), patients with at least one ≥G3 AE (37.1% vs. 21.1%). In conclusion, our study is to the first to evaluate clinical outcomes according to MRP in a high risk real-world cohort of patients treated exclusively with the proteasome inhibitor-based VCD therapy. Our study demonstrated a trend for worse OS in addition to worse AE outcomes in the frail group, but no difference in PFS with this fixed-duration therapy. MRP is an easy-to-use tool in clinical practice; its prognostic value was validated in the real-world in a large cohort of patients from the Danish Registry. Further evaluation of MRP in the real-world when continuous therapies are used, can further support the generalisability of its prognostic value in elderly myeloma patients.

Infections in relapsed myeloma patients treated with isatuximab plus pomalidomide and dexamethasone during the COVID-19 pandemic: Initial results of a UK-wide real-world study.

OBJECTIVES: There are no real-world data describing infection morbidity in relapsed/refractory myeloma (RRMM) patients treated with anti-CD38 isatuximab in combination with pomalidomide and dexamethasone (IsaPomDex). In this UK-wide retrospective study, we set out to evaluate infections experienced by routine care patients who received this novel therapy across 24 cancer centres during the COVID-19 pandemic. METHODS: The primary endpoint was infection morbidity (incidence, grading, hospitalization) as well as infection-related deaths. Secondary outcomes were clinical predictors of increased incidence of any grade (G2-5) and high grade (≥G3) infections. RESULTS: In a total cohort of 107 patients who received a median (IQR) of 4 cycles (2-8), 23.4% of patients experienced ≥1 any grade (G2-5) infections (total of 31 episodes) and 18.7% of patients experienced ≥1 high grade (≥G3) infections (total of 22 episodes). Median time (IQR) from start of therapy to first episode was 29 days (16-75). Six patients experienced COVID-19 infection, of whom 5 were not vaccinated and 1 was fully vaccinated. The cumulative duration of infection-related hospitalizations was 159 days. The multivariate (MVA) Poisson Regression analysis demonstrated that a higher co-morbidity burden with Charlson Co-morbidity Index (CCI) score ≥4 (incidence rate ratio (IRR) = 3, p = 0.012) and sub-optimal myeloma response less than a partial response (

Efficacy of Isatuximab With Pomalidomide and Dexamethasone in Relapsed Myeloma: Results of a UK-Wide Real-World Dataset.

Real-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma patients have not been reported. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 routine care cancer centers. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) for patients who achieved an objective response (≥partial response [PR]), and adverse events (AEs). In a total cohort 107 patients, median follow up (interquartile range [IQR]) was 12.1 months (10.1-18.6 mo), median age (IQR) was 69 years (61-77). Median (IQR) Charlson Comorbidity Index (CCI) score was 3 (2-4); 43% had eGFR <60 mL/min. Median (IQR) number of prior therapies was 3 (3-3). Median (IQR) number of IsaPomDex cycles administered was 7 (3-13). ORR was 66.4%, with responses categorized as ≥ very good partial response: 31.8%, PR: 34.6%, stable disease: 15.9%, progressive disease: 15%, and unknown 2.8%. Median PFS was 10.9 months. Median DOR was 10.3 months. There was no statistical difference in median PFS by age (<65: 10.2 versus 65-74 13.2 versus ≥75: 8.5 mo, log-rank P = 0.4157), by CCI score (<4: 10.2 mo versus ≥4: 13.2, log-rank P = 0.6531), but inferior PFS was observed with renal impairment (≥60: 13.2 versus <60: 7.9 mo, log-rank P = 0.0408). Median OS was 18.8 months. After a median of 4 cycles, any grade AEs were experienced by 87.9% of patients. The most common ≥G3 AEs were neutropenia (45.8%), infections (18.7%), and thrombocytopenia (14%). Our UK-wide IsaPomDex study demonstrated encouraging efficacy outcomes in the real world, comparable to ICARIA-MM trial.

A Case of Meningococcal and HSV-2 Meningitis in a Patient Being Treated with Ustekinumab for Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory papulosquamous dermatosis affecting both adults and children. Six subtypes of PRP have been described. Recently, the management of PRP with biologic immunosuppressive agents regularly used in psoriasis has been supported by several case reports and series. Ustekinumab is an anti-IL12/23 IgG1 kappa human monoclonal antibody. It has been approved for the treatment of Crohn's disease, plaque psoriasis, psoriatic arthritis and ulcerative colitis. It has also been reported to be effective as an off-label treatment for PRP. Current data are equivocal regarding infectious disease risk with ustekinumab administration. We describe a case of meningococcal and HSV-2 infection of the central nervous system in a patient being treated with ustekinumab for PRP. LEARNING POINTS: The administration of biologic immunosuppressive agents can result in severe life-threatening infections.Research is required on the infection potential of ustekinumab.Physicians should be aware of the possibility of infectious disease when prescribing biologic agents.Vaccination is essential in immunosuppressed adults.

Orbital metastases of invasive lobular breast carcinoma.

Breast cancer is the main site of origin of orbital metastatic disease. Although invasive lobular breast carcinoma accounts for 10-15% of all breast cancer cases, it has been noticed that it metastasizes to the orbit more often compared to breast cancer of no special type (NST). The pathogenesis of this metastasis is not entirely understood; however, it seems that the unique tissue-specific characteristics of orbital microenvironment might contribute to metastatic disease in this particular site. Given the increasing survival of breast cancer patients and the prolonged metastatic potential of invasive lobular breast carcinoma, it is possible that the incidence of this rare metastasis might increase in the future. The purpose of this review is to present clinical manifestations, immunohistochemical characteristics and therapeutic options for orbital metastases from invasive lobular carcinoma.

The Role of Anxiety in Simulation-Based Dexterity and Overall Performance: Does It Really Matter?

BACKGROUND: Essential Skills in the Management of Surgical Cases (ESMSC) is an international undergraduate surgical masterclass which combines ex vivo, dry lab and high fidelity in vivo simulation-based learning (SBL). It consists of 32 stations of skills-based learning, including open reduction internal fixation (ORIF) of fractures. Current literature suggests early involvement in skills-based learning at the undergraduate level is vital. AIMS: To compare students' dexterity and skills-based performance with demographic and educational background parameters. METHODS: 112 medical students from European Union countries including the United Kingdom, Germany, Greece, Cyprus, Germany, and Bulgaria were selected from a competitive pool of candidates to attend the course. Students undertook ORIF in an ex vivo swine model, and in a simulated fracture on a bamboo rod. Skills-based performance was assessed by two consultant surgeons with validated direct observation of procedural skills (DOPS) forms. Anxiety was self-assessed using the Westside Anxiety Scale prior to the ORIF stations. Dexterity was measured with the O'Connor tweezer dexterity test. RESULTS: Female students had significantly higher dexterity scores (median difference 7, p =.003). Right-handed students achieved higher dexterity than left-handed students (median difference 7, p =.043). There was no difference in students' performance across different medical schools, and across year groups (p <.05 for any correlation). Self-reported anxiety was not correlated with high fidelity skills-based performance (r = 0.032, p =.74). CONCLUSION: Anxiety does not seem to play a significant role in Simulation Skills-Based learning. Undergraduate surgical curricula should incorporate SBL-based modules to enhance practical skills learning and motivate future orthopedic surgeons.

Introducing In Vivo Dissection Modules for Undergraduate Level Trainees: What Is the Actual Benefit and How Could We Make It More Efficient?

Essential Skills in the Management of Surgical Cases (ESMSC) is an international wet lab simulation course aimed at undergraduate students. It combines basic science workshops, case-based lectures and ex vivo skills modules, as well as in vivo dissections using a swine model. This study aims to evaluate the effectiveness of high-fidelity In Vivo Simulation-Based Learning for undergraduate level trainees. Also our goal was to compare the skill-based performance of final year students vs. more junior-level ones. Forty undergraduate delegates at clinical rotation level (male = 28, female = 12, mean age = 23.12, 22-24, SD = 0.69) attended this 2-day course in Athens. N = 1 (2.5 %) was year 3, N = 4 (10 %) were year 4, N = 23 (57.5 %) were year 5 and N = 12 (30 %) were year 6. N = 30 (75 %) came from Hellenic universities, N = 8 (20 %) from the UK and N = 2 (5 %) from Germany. N = 20 (50 %) attended the in vivo dissections module first, and then the ex vivo one (type A rotation), whereas N = 20 followed the reverse training sequence with the ex vivo dissection first, followed by the in vivo one (type B rotation). The mean global rating scores for type A rotation were better in both the in vivo by 0.10 (2.40 vs. 2.30) and ex vivo modules by 0.15 (2.85 vs. 2.70), though it did not reach statistical significance (p > 0.05). Furthermore, the mean improvement of performance, in the laparoscopic skills station for the type A rotation, was better compared to type B by 0.351 (2.00 vs. 1.65, p = 0.003). Year 6 students performed better in the laparoscopic station (2.00 vs. 1.75, p = 0.059), whereas years 3, 4 and 5 performed better in the in vivo (2.42 vs. 2.16, p = 0.157) as well as the ex vivo dissections (2.78 vs. 2.75, p = 0.832), though none of those comparisons reached statistical significance. Delegates seemed to appreciate and enjoy the in vivo dissections as reflected in the feedback (8.67/10, min = 6 and max = 10, SD = 1.79). Although medical students seem to appreciate in vivo dissections modules, currently, further evidence is needed to support their recommendation in the undergraduate level. Surgical skills should be part of the undergraduate curriculum to improve final year students' performance in the theatre.

Is In-Vivo laparoscopic simulation learning a step forward in the Undergraduate Surgical Education?

BACKGROUND: Essentials Skills in the Management of Surgical Cases - ESMSC is an International Combined Applied Surgical Science and Wet Lab course addressed at the Undergraduate level. Laparoscopic Skills is a fundamental element of Surgical Education and various Simulation-Based Learning (SBL) models have been endorsed. This study aims to explore if there is any significant difference in delegates' performance depending on whether they completed In Vivo module prior to the equivalent in the laparoscopic simulator. MATERIALS AND METHODS: 37 Medical Students from various EU countries were divided in 2 groups, and both completed the "Fundamentals in Laparoscopic Surgery" module in the Dry-lab Laparoscopic Simulator as well as the same module "In Vivo" on a swine model. Group A (18 students, 48.6%) completed the "Fundamentals in Laparoscopic Surgery - FLS" module prior to the "In Vivo", whereas group B completed the "In Vivo" module first. Direct Observation of Procedural Skills (DOPS) were used to assess delegates' performance. RESULTS: The mean DOPS scores for the "FLS" and "In Vivo" models were 2.27 ± 0.902 and 2.03 ± 0.833, respectively, and the delegates' performance was not statistically significantly different between them (p = 0.128). There was no statistically significant difference in the scores among different gender, year of study, school and handedness groups. The alteration in the sequence between Dry-lab "FLS" and "In Vivo" modules did not affect the performance in neither the "FLS" nor the "In Vivo" models. CONCLUSIONS: The inexpensive, but low-fidelity "FLS" model could serve an equal alternative Simulation-Based Learning model for the early undergraduate training. Our study demonstrated that high fidelity In Vivo simulation for laparoscopic skills does not affect significantly the improvement in the delegates' performance at the undergraduate level. Further studies should be conducted to identify at which stage of training should high fidelity simulation be introduced.

Promoting Undergraduate Surgical Education: Current Evidence and Students' Views on ESMSC International Wet Lab Course.

BACKGROUND: Undergraduate Surgical Education is becoming an essential element in the training of the future generation of safe and efficient surgeons. Essential Skills in the Management of Surgical Cases (ESMSC), is an international, joint applied surgical science and simulation-based learning wet lab course. METHODS: We performed a review of the existing literature on the topic of undergraduate surgical education. Following that, we analyzed the feedback questionnaire received 480 from 2 recent series of ESMSC courses (May 2015, n = 49 and November 2015, n = 40), in order to evaluate European Union students' (UK, Germany, Greece) views on the ESMSC course, as well as on the undergraduate surgical education. Results Using a 10 point graded scale, the overall ESMSC concept was positively evaluated, with a mean score of 9.41 ± 0.72 (range: 8-10) and 8.94 ± 1.1 (range: 7-10). The majority of delegates from both series [9.86 ± 0.43 (range: 8-10) and 9.58 ± 0.91 (range: 6-10), respectively] believed that ESMSC should be incorporated in the undergraduate surgical curriculum. Comparison of responses from the UK to the Greek Medical Student, as well as the findings from the third and fourth year versus the fifth and sixth year Medical Students, revealed no statistically significant differences pertaining to any of the questions (p > 0.05). CONCLUSIONS: Current evidence in the literature supports the enhancement of surgical education through the systematic use of various modalities that provide Simulation-Based Training (SBT) hands-on experience, starting from the early undergraduate level. The findings of the present study are in agreement with these previous reports.