Impact of Ultra High-risk Genetics on Real-world Outcomes of Transplant-eligible Multiple Myeloma Patients.

Refined prediction of early relapse following standard-of-care (SoC) autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) could inform real-world risk-stratified post-ASCT strategies. We investigated the impact of double hit genetics (≥2 adverse markers: t(4;14), t(14;16), t(14;20), gain(1q), del(17p)) on outcome in 139 NDMM patients who underwent SoC ASCT between January 2014 and October 2019 at our center. Double hit genetics were associated with a significantly shortened progression-free survival (hazard ratio [HR] = 4.27, P < 0.001) and overall survival (HR = 4.01, P = 0.03), and characterized most early relapses. Our results support the real-world utility of extended genetic profiling for improved risk prediction in NDMM.

Outcomes After Donor Lymphocyte Infusion in Patients With Hematological Malignancies: Donor Characteristics Matter.

In the context of T-cell depletion, failing to achieve full donor chimerism (FDC) entails higher risk of graft loss and disease relapse. Donor lymphocyte infusion (DLI) is an adoptive immunotherapy for mixed chimerism (MC) or relapsed disease after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, little is known of factors associated with attaining FDC or disease remission. We carried out a retrospective study with 100 adult patients to identify patient and donor factors that can predict achievement of FDC and disease remission and describe complications after DLI. Indications for DLI were T-cell MC in 61 patients and relapsed disease in 39 patients. Forty patients (65.6%) with MC attained T-full donor chimerism (T-FDC), with higher responses seen in patients whose donors were female (81.5% versus 52.9%, P = .004) and cytomegalovirus negative (76.5% versus 52%, P = .004). However, only patients with younger donors (<30 years old) compared to older donors (94.4% versus 53.5%, P = .013) and those attaining unfractionated whole blood (UWB) FDC after DLI (76.6% versus 28.6%, P < .001) had a survival benefit and subsequently a better graft-versus-host disease (GvHD)-free/relapse-free survival. Nineteen of 39 patients (48.7%) with relapsed disease achieved remission after DLI. In this cohort, attaining T-FDC impacted favorably in disease control (76.7% versus 12.5%, P = .012) and improved survival (45.5% versus 12.5%, P = .007). In the whole population, the cumulative incidence of acute GvHD (aGvHD) at day 100 after DLI was 23%, and chronic GvHD (cGvHD) at 1 year after DLI was 22%. In the whole population, donor age was also a determining factor for aGvHD, because patients with younger donors had a lower incidence of aGvHD (8% versus 36%, P = .021). The cGvHD was more likely to occur in patients who converted to T-FDC (34% versus 10.3%, P = .025). Donor characteristics are increasingly considered when deciding approaches for HSCT. Donor age should be considered when planning HSCT, as well as doses and scheduling of DLI. As per our experience, this should be done alongside T/UWB chimerism to achieve the maximal clinical benefit with less associated toxicity. Selection of younger male donors from stem cell registries can minimize the risk of GvHD and improve survival.

Serologic Responses following a Single Dose of SARS-Cov-2 Vaccination in Allogeneic Stem Cell Transplantation Recipients.

Immunocompromised individuals were not included in formal trials of SARS-CoV-2 mRNA vaccines. Subsequent studies in patients with hematologic malignancies and solid organ transplantation recipients suggest inferior responses to vaccination. We determined antibody responses to a single dose of vaccines in one of the most vulnerable patient groups, allogeneic hematopoietic cell transplantation (allo-HCT) recipients. Pfizer-BioNTech (PB) or AstraZeneca (AZ) SARS-CoV-2 vaccines were administered at least 3 months post-transplantation to 55 adult allo-HCT recipients. We found that older age and concurrent use of immunosuppressive medications were significantly associated with lack of antibody response to vaccination. Only 21% of patients on systemic immunosuppression mounted a response, compared with 58% of patients not on immunosuppression (P = .006). We also show that responses to the AZ vaccine may be superior to responses to the PB vaccine in this cohort. These findings highlight the need for novel immunogenic vaccine formulations and schedules in these highest-risk patients, as well as continued public healthy safety measures to protect the most vulnerable members of our society.

Rozrolimupab, a first-in-class recombinant monoclonal antibody product for primary immune thrombocytopaenia.

INTRODUCTION: Over the last decade the field of medicine has dramatically changed with the introduction of biological therapies, among which monoclonal antibodies play a pivotal role in the management of many diseases. Rozrolimupab is the first of a new class of recombinant human monoclonal antibody mixtures, consisting of 25 genetically unique IgG1 antibodies, targeted against the RhD erythrocyte antigen. It is currently being investigated for its use in the treatment of primary immune thrombocytopenia. AREAS COVERED: This article outlines the impetus for the development of rozrolimupab in the treatment of ITP. In addition, the literature regarding the development of rozrolimupab and the recent clinical trials involving this agent are also reviewed. EXPERT OPINION: Although rozrolimupab is only in the very early phases of clinical development we believe that this agent represents a very interesting agent not only for its potential benefits in the management of ITP but potentially for the prevention of haemolytic disease of the foetus and newborn.

Molecular pharmacology of cancer therapy in human colorectal cancer by gene expression profiling.

Global gene expression profiling has potential for elucidating the complex cellular effects and mechanisms of action of novel targeted anticancer agents or existing chemotherapeutics for which the precise molecular mechanism of action may be unclear. In this study, decreased expression of genes required for RNA and protein synthesis, and for metabolism were detected in rectal cancer biopsies taken from patients during a 5-fluorouracil infusion. Our observations demonstrate that this approach is feasible and can detect responses that may have otherwise been missed by conventional methods. The results suggested new mechanism-based combination treatments for colorectal cancer and demonstrated that expression profiling could provide valuable information on the molecular pharmacology of established and novel drugs.