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.

An assessment of the management of anaemia in acute care settings in the United Kingdom: The value of a collaborative approach.

OBJECTIVES: Patients presenting to acute care settings with anaemia are at risk of inadequate investigation and inappropriate blood transfusion. In collaboration with Haematology Specialty Trainee Audit and Research (HaemSTAR), this study set out to assess current red blood cell (RBC) transfusion practice and anaemia management in acute care settings across the United Kingdom. METHODS AND RESULTS: Fifteen different hospitals participated in the study over a period of a month beginning 01 January 2020. Eight-hundred and twenty-eight eligible patients presenting to acute care settings with anaemia received RBC transfusions during this period. Of these, 159 (19.2%) received inappropriate transfusions according to National Institute for Health and Care Excellence guidelines, and 257 (31%) could have been treated with alternatives to transfusion. One-hundred and fifty-four (18.6%) did not have a cause for their anaemia identified by the time they were discharged from hospital, and in over 50% of these cases that was because of inadequate investigation with blood tests, specialist investigation or referral, or both. CONCLUSION: This study found that the appropriateness of transfusion and investigation of anaemia in acute care settings warrant improvement and also demonstrates the value of HaemSTAR in facilitating time-efficient collection of high-quality data.

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.

Platelet transfusion: Alloimmunization and refractoriness.

The transfusion of platelets for both prophylaxis and treatment of bleeding is relevant to all areas of medicine and surgery. Historically, guidance regarding platelet transfusion has been limited by a lack of good quality clinical trials and so has been based largely on expert opinion. In recent years however there has been renewed interest in methods to prevent and treat hemorrhage, and the field has benefited from a number of large clinical trials. Some studies, such as platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH) and platelets for neonatal transfusion Study 2 (PLANET-2), have reported an increased risk of harm with platelet transfusion in specific patient groups. These studies suggest a wider role of platelets beyond hemostasis, and highlight the need for further clinical trials to better understand the risks and benefits of platelet transfusions. This review evaluates the indications for platelet transfusion, both prophylactic and therapeutic, in the light of recent studies and clinical trials. It highlights new developments in the fields of platelet storage and platelet substitutes, and novel ways to avoid complications associated with platelet transfusions. Lastly, it reviews initiatives designed to reduce inappropriate use of platelet transfusions and to preserve this valuable resource for situations where there is evidence for their beneficial effect.