Emerging combination therapies for the management of multiple myeloma: the role of elotuzumab

Wei-Chih Chen,1 Abraham S Kanate,2,3 Michael Craig,2,3 William P Petros,1,3 Lori A Hazlehurst1–3 1Department of Pharmaceutical Sciences, School of Pharmacy, 2Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, 3West Virginia University Cancer Institute, Morgantown, WV, USA Abstract: Treatment options for patients with multiple myeloma (MM) have increased during the past decade. Despite the significant advances, challenges remain on which combination strategies will provide the optimal response for any given patient. Defining optimal combination strategies and corresponding companion diagnostics, that will guide clinical decisions are required to target relapsed or refractory multiple myeloma (RRMM) in order to improve disease progression, survival and quality of life for patients with MM. Elotuzumab is a humanized monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7), approved by the US Food and Drug Administration (FDA) in 2015 and the European Medicines Agency in 2016 for the treatment of MM. SLAMF7 is expressed in normal and malignant plasma cells and has lower expression on natural killer (NK) cells. Experimental evidence indicates that elotuzumab exhibits anti-myeloma activity through 1) antibody-dependent cell-mediated cytotoxicity, 2) enhancing NK cells cytotoxicity and 3) interfering with adhesion of MM cells to bone marrow stem cells (BMSCs). Although elotuzumab has no single agent activity in patients with RRMM who have received one to three prior therapies, the combination of elotuzumab with anti-myeloma agents, such as immunomodulatory drugs-lenalidomide, or proteasome inhibitors (PIs)-bortezomib, remarkably improved the overall response rates and progression-free survival in MM patients with only minimal incremental toxicity. In brief, the clinical data for elotuzumab indicate that targeting SLAMF7 in combination with the use of conventional therapies is feasible and effective with a tolerable safety profile for the treatment of RRMM. Keywords: elotuzumab, SLAMF7, relapsed/refractory multiple myeloma (RRMM

Real‐world experience: Introduction of T cell replete haploidentical transplantations in a single center

OBJECTIVES: The aim of this study was to describe real‐world data on outcomes of T cell replete haploidentical hematopoietic stem cell transplantation (HSCT) after the introduction of this modality in a single center and to compare them with different donor types. METHOD: Outcomes of 30 consecutive patients with hematological malignancies that received T cell replete haploidentical HSCT with posttransplantation cyclophosphamide (PTCY) from 2016 to 2018 in our center were analyzed and compared to the outcome of human leukocyte antigen (HLA)‐related and unrelated matched donor HSCT (n = 97) and to a historical cohort of T cell depleted haploidentical HSCT (n = 11). RESULTS: One year graft‐versus‐host‐free, relapse‐free survival in haploidentical HSCT was comparable with other donor types (haplo 40%, matched related donor [MRD] 33%, matched unrelated donor [MUD] 25%, p = 0.55). Non relapse mortality was high in haploidentical HSCT (50%), mostly due to infectious complications. However, relapse rates were only 3%, and OS and progression‐free survival after 1 year were 47% and thereby also similar to HLA‐matched HSCT in our center (MRD 53%, MUD 48%). CONCLUSION: Our data show that T cell replete haploidentical HSCT has similar outcomes to HLA identical HSCT after introduction in our center. More strict adaptation on infection prevention was a crucial aspect of our learning curve. Overall, this type of transplantation is a feasible option when lacking an HLA‐identical donor. This option has advantages over an unrelated donor as it brings less logistical challenges than MUD transplantations

CD3+ graft cell count influence on chronic GVHD in haploidentical allogeneic transplantation using post-transplant cyclophosphamide

The effects of graft or donor characteristics in haploidentical hematopoietic cell transplantation (HCT) using post-transplant cyclophosphamide (PT-Cy) are largely unknown. In this multicenter retrospective study we analyzed the correlations between graft cell composition (CD34+, CD3+) and donor features on transplant outcomes in 234 patients who underwent HCT between 2010 and 2016. On multivariate analysis, the use of peripheral blood stem cells (PBSC) was associated with an increased incidence of grade 2\u20134 acute GVHD [HR 1.94, 95% confidence Interval (CI) = 1.01\u20133.98, p = 0.05]. An elevated CD3+ graft content was associated with an increased incidence of all-grade chronic GVHD [HR 1.36 (95% CI = 1.06\u20131.74), p = 0.01]. This effect was confirmed only for the PBSC graft group. A higher CD34+ graft content had a protective role on non-relapse mortality [HR 0.78 (95% CI = 0.62\u20130.96), p = 0.02] but this was confirmed only for the bone marrow (BM)-derived graft cohort. Donor characteristics did not influence any outcomes. GVHD prophylaxis should be modulated accordingly to CD3+ graft content, especially when a PBSC graft is used. These results need further validation in prospective trials