Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma.

Daratumumab, a human immunoglobulin G1 kappa monoclonal antibody that targets CD38, is currently approved as monotherapy and in varying combinations with approved anti-myeloma regimens in both newly diagnosed multiple myeloma and relapsed refractory multiple myeloma. Originally developed for intravenous administration, the subcutaneous formulation of daratumumab (daratumumab and hyaluronidase-fihj) was recently approved by the US Federal Drug Administration and European Commission in 2020. In clinical trials, compared with the intravenous formulation, subcutaneous daratumumab (Dara-SC) has significantly shorter administration time (median first dose 7 h versus 3-5 min, respectively), lower rates of infusion-related reactions (median first dose 50% versus less than 10%, respectively), and lower volume of infusion (median 500-1000 ml versus 15 ml, respectively). Otherwise, the pharmacokinetics, safety profile, and efficacy are comparable. This review summarizes the pivotal trials that led to the approval of Dara-SC, highlights important clinical considerations for the use of Dara-SC, and provides practical guidelines for the administration of Dara-SC in the clinic

A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma.

Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively. High-risk molecular findings were present in 17 (63%) patients. Responses included 2 complete responses (CRs), 4 very good partial responses (VGPRs), 5 partial responses (PRs), and 9 minimal responses (MRs) for an overall response rate of 41%, clinical benefit rate of 74%, and a disease control rate of 96%. The median progression-free survival (PFS) was 7.1 months. In the 22 lenalidomide-refractory patients, there were 1 CR, 4 VGPRs, 3 PRs, and 7 MRs, with a median PFS of 6.5 months. Median overall survival was not reached. Grade 3/4 toxicities were primarily hematologic. Gene expression profiling of enrollment tumor samples revealed a set of 1989 genes associated with short (<90 days) PFS to therapy. MAGEA1 RNA and protein expression were correlated with short PFS, and laboratory studies demonstrated a role for MAGE-A in resistance to panobinostat-induced cell death. FRD demonstrates durable responses, even in high-risk, lenalidomide-refractory patients, indicating the essential role of panobinostat in attaining responses. MAGEA1 expression may represent a functional biomarker for resistance to panobinostat. In contrast to PANORAMA 1, there were no significant GI toxicities and primarily expected hematologic toxicities. This trial was registered at www.clinicaltrials.gov as #NCT00742027

Do attitudes and behavior of health care professionals exacerbate health care disparities among immigrant and ethnic minority groups? An integrative literature review

Objectives Recent investigations of ethnicity related disparities in health care have focused on the contribution of providers’ implicit biases. A significant effect on health care outcomes is suggested, but the results are mixed. The purpose of this integrative literature review is to provide an overview and synthesize the current empirical research on the potential influence of health care professionals’ attitudes and behaviors towards ethnic minority patients on health care disparities. Design Integrative literature review. Data sources Four internet-based literature indexes – MedLine, PsychInfo, Sociological Abstracts and Web of Science – were searched for articles published between 1982 and 2012 discussing health care professionals’ attitudes or behaviors towards ethnic minority patients. Review methods Thematic analysis was used to synthesize the relevant findings. Results We found 47 studies from 12 countries. Six potential barriers to health care for ethnic minorities were identified that may be related to health care professionals’ attitudes or behaviors: Biases, stereotypes and prejudices; Language and communication barriers; Cultural misunderstandings; Gate-keeping; Statistical discrimination; Specific challenges of delivering care to undocumented migrants. Conclusions Data on health care professionals’ attitudes or behaviors are both limited and inconsistent. We thus provide reflections on methods, conceptualization, interpretation and the importance of the geographical or socio-political settings of potential studies. More empirical data is needed, especially on health care professionals’ attitudes or behaviors towards (irregular) migrant patients

Rejoinder to Karen Lutfey Spencer

Wild V, Drewniak D, Sauer C, Krones T. Rejoinder to Karen Lutfey Spencer. Social Science & Medicine. 2017;172:19-20