CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges.

The therapeutic landscape of multiple myeloma (MM) has benefited from an emergence of novel therapies over the last decade. By inducing T-cell kill of target cancer cells, chimeric antigen receptor (CAR) T-cell therapies have improved outcomes of patients with hematologic malignancies. B-cell maturation antigen (BCMA) is the current target antigen of choice for most CAR T-cell products under investigation for MM. However, their shortcomings deal with logistical and clinical challenges, including limited availability, manufacturing times, and toxicities. This article provides an overview of recently developed and investigational CAR T-cell therapies for MM, highlighting current evidence and challenges.

Acquired Coagulopathy With Immune Checkpoint Inhibitors: An Underrecognized Association Between Inflammation and Coagulation.

INTRODUCTION: Immune-related adverse events affecting virtually every organ system have been described in individuals receiving immune checkpoint inhibitors. The spectrum of hematologic adverse effects is diverse and includes autoimmune cytopenias, hemolysis, or inhibition of coagulation factors. The interplay of inflammation and the coagulation cascade is complex, and immune checkpoint inhibitors can induce coagulopathy by disrupting the intricate link between these pathways. METHODS: We report acquired coagulopathy in two patients treated with the programmed death-ligand 1 antibodies, atezolizumab and avelumab, respectively. Clinical findings and results of extensive laboratory workup are reported. We hypothesize that cytokine release is a potential pathologic mechanism responsible for acquired coagulopathy. RESULTS: Symptoms included fever, fatigue, and disorientation in one patient and fever, myalgias, and skin rash in the other. Laboratory features included an abnormal coagulation profile; low fibrinogen levels; and elevated D-dimer, ferritin, and triglycerides. Treatment consisted of intravenous glucocorticoids in both cases and the use of fresh frozen plasma, cryoprecipitate, and clotting factor support in one patient. CONCLUSIONS: Recognition of acquired coagulopathy as a complication of immunotherapy and its aggressive management are crucial to reduce morbidity and mortality associated with this condition.

Ifosfamide-Induced Metabolic Encephalopathy in 2 Patients With Cutaneous T-Cell Lymphoma Successfully Treated With Methylene Blue.

Ifosfamide, an alkylating agent used in cancer treatments, can cause neurotoxicity. The clinical presentation can range from mild symptoms such as acute confusion to non-convulsive seizures, severe irreversible coma, and death. The benefit of methylene blue use in treating ifosfamide-induced metabolic encephalopathy is not well established. In this article, we present 2 cases of ifosfamide-induced metabolic encephalopathy responsive to methylene blue treatment.

When there is no match, the game is not over: Alternative donor options for hematopoietic stem cell transplantation in sickle cell disease.

Many patients with sickle cell disease experience severe morbidity and early mortality. The only curative option remains hematopoietic stem cell transplantation. Although HLA-matched sibling transplantation has been very successful for adults and children, the vast majority of patients with sickle cell disease do not have an HLA-matched sibling. Alternative donor options include haploidentical, unrelated umbilical cord blood, and matched unrelated donor transplantation. This report summarizes major alternative donor transplantation studies reported to date and ongoing and upcoming clinical trials. We conclude that when there is no HLA-match, all these approaches should be systematically considered before ruling out the option of hematopoietic stem cell transplantation.

Curative therapies: Allogeneic hematopoietic cell transplantation from matched related donors using myeloablative, reduced intensity, and nonmyeloablative conditioning in sickle cell disease.

Sickle cell disease (SCD) chronically damages multiple organs over the lifetime of affected individuals. Allogeneic hematopoietic cell transplantation (allo-HCT) is the most studied curative intervention. Fully matched related marrow, peripheral blood derived, or cord blood HCT have the best transplant outcome for symptomatic patients with SCD. For patients with asymptomatic or milder disease who have this donor option available, risks and benefits of HCT should be discussed among the patient, family, treating hematologist, and transplant physician, and decision to proceed to HCT should be individualized. Myeloablative conditioning with busulfan, cyclophosphamide, and ATG has been a commonly employed regimen for children and young adults. Recently, low intensity conditioning with low dose total body irradiation and alemtuzumab is emerging as an efficacious and safe regimen for adults, young adults, and possibly children. Mixed donor chimerism (minimum ≥20% myeloid cells), from myeloablative or nonmyeloablative conditioning regimen, produces robust normal donor erythropoiesis and is sufficient to provide a clinical cure. The proportion of patients remaining on immunosuppression beyond 2 years post-HCT is likely <10% with either myeloablative or low intensity regimens. Late effects from myeloablative or reduced intensity conditioning, or from several more months of immunosuppression in low intensity conditioning may be less common than those observed in HCT for malignant indications. Nonmyeloablative approaches with low toxicities should be the focus of future research efforts. Prevention of GVHD is a shared goal in all approaches of allo-HCT in SCD.