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Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not respond to or who have progressive disease after salvage therapies have a poor prognosis. Loncastuximab tesirine is a CD19-directed antibody–drug conjugate with encouraging phase 1 single-agent antitumour activity and acceptable safety in non-Hodgkin lymphoma. We aimed to evaluate the antitumour activity and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL. We did a multicentre (28 hospital sites in the USA, UK, Italy, and Switzerland), open-label, single-arm, phase 2 trial (LOTIS-2) in patients aged 18 years or older with relapsed or refractory DLBCL after two or more multiagent systemic treatments, who had measurable disease and Eastern Cooperative Oncology Group performance status 0–2. Eligible patients received loncastuximab tesirine intravenously on day 1 of each 21-day cycle, at 150 μg/kg for two cycles, then 75 μg/kg thereafter, for up to 1 year or until disease relapse or progression, unacceptable toxicity, death, major protocol deviation, pregnancy, or patient, investigator, or sponsor decision. The primary endpoint was overall response rate assessed by central review. Primary antitumour activity and safety analyses were done in the as-treated population (patients who received at least one dose of loncastuximab tesirine), when all responding patients had at least 6 months of follow-up after initial documented response. Enrolment is complete. This trial is registered with ClinicalTrials.gov, NCT03589469. Between Aug 1, 2018, and Sept 24, 2019, 184 patients were assessed for eligibility and 145 (79%) were enrolled and received at least one dose of loncastuximab tesirine, including patients with high-risk characteristics for poor prognosis, such as double-hit, triple-hit, transformed, or primary refractory DLBCL. 70 of 145 patients had complete or partial response (overall response rate 48·3% [95% CI 39·9–56·7]); 35 had complete response and 35 had partial response. The most common grade 3 or higher treatment-emergent adverse events were neutropenia (37 [26%] of 145 patients), thrombocytopenia (26 [18%]), and increased gamma-glutamyltransferase (24 [17%]). Serious adverse events were reported in 57 (39%) of 145 patients. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. Loncastuximab tesirine has substantial single-agent antitumour activity and produces durable responses with an acceptable safety profile, potentially offering a new therapeutic option for heavily pretreated patients with relapsed or refractory DLBCL. ADC Therapeutics.

In this trial, 1-year GVHD-free, relapse-free survival after stem-cell transplantation was 52.7% in the cyclophosphamide–tacrolimus–mycophenolate mofetil group and 34.9% in the tacrolimus–methotrexate group.

Multiple myeloma (MM) is a plasma cell malignancy expressing B cell maturation antigen (BCMA). Elranatamab, a bispecific antibody, engages BCMA on MM and CD3 on T cells. The MagnetisMM-1 trial evaluated its safety, pharmacokinetics and efficacy. Primary endpoints, including the incidence of dose-limiting toxicities as well as objective response rate (ORR) and duration of response (DOR), were met. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). Eighty-eight patients with relapsed or refractory MM received elranatamab monotherapy, and 55 patients received elranatamab at efficacious doses. Patients had received a median of five prior regimens; 90.9% were triple-class refractory, 29.1% had high cytogenetic risk and 23.6% received prior BCMA-directed therapy. No dose-limiting toxicities were observed during dose escalation. Adverse events included cytopenias and cytokine release syndrome. Exposure was dose proportional. With a median follow-up of 12.0 months, the ORR was 63.6% and 38.2% of patients achieving complete response or better. For responders, the median DOR was 17.1 months. All 13 patients evaluable for minimal residual disease achieved negativity. Even after prior BCMA-directed therapy, 53.8% achieved response. For all 55 patients, median PFS was 11.8 months, and median OS was 21.2 months. Elranatamab achieved durable responses, manageable safety and promising survival for patients with MM. ClinicalTrials.gov Identifier: NCT03269136 . In the first-in-human trial of elranatamab, patients with refractory or relapsed multiple myeloma who received the bispecific antibody against BCMA and CD3 experienced no dose-limiting toxicities during dose escalation, and the agent showed promising clinical efficacy.

Glanzmann's thrombasthenia (GT) is a genetic platelet surface receptor disorder of GPIIb/IIIa (ITG αIIbβ3), either qualitative or quantitative, which results in faulty platelet aggregation and diminished clot retraction. Spontaneous mucocutaneous bleeding is common and can lead to fatal bleeding episodes. Control and prevention of bleeding among patients with GT is imperative, and remains challenging. Local measures, including anti-fibrinolytic therapy, with or without platelet transfusions, used to be the mainstay of therapy. However, in recent years the use of recombinant factor VIIa (rFVIIa) has increased significantly, with excellent response rates in treating and preventing hemorrhage among GT patients. Gene therapy and stem cell transplantation offer a potential cure of this disease, but both are costly and remain experimental at this point. This manuscript offers a comprehensive review of our understanding of GT and the available treatment options.

The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4–11%), relapse (REL) 76% (69–82%), progression-free survival (PFS) 17% (13–23%), and overall survival (OS) 28% (22–35%). Karnofsky performance status (KPS) > 90 and ≥very good partial response (VGPR) predicted superior OS in multi-variate analysis for auto-HCT. For allo-HCT, the 4-year outcomes were: NRM 12% (5–21%), REL 69% (56–81%), PFS 19% (10–31%), and OS 31% (19–44%). Compared with prior CIBMTR pPCL patients (1995–2006), inferior survival was noted in the current cohort (3-year OS, 39% vs. 38% in allo-HCT, and 62% vs. 35% in auto-HCT) respectively. However, we noted an increased HCT utilization, from 12% (7–21%) in 1995 to 46% (34–64%) in 2009 using SEER data (available till 2009). Despite modern induction translating to higher proportion receiving HCT, the outcomes remain poor in pPCL patients, mainly derived by high relapse rates post-HCT.

Fever is a common early complication after infusion of stem cells in patients undergoing T-replete HLA haploidentical transplantation using post-transplant cyclophosphamide (PTCY). We analyzed the records of 172 haploidentical transplant patients to identify risk factors and to assess the impact of such fevers on transplant morbidity and mortality. One hundred and seventy-two patients received haploidential hematopoietic stem cell transplantation (haplo-HSCT) using PBSC (n = 103) or marrow (n = 69) grafts. One hundred and forty patients (81%) experienced fever (T ≥ 100.5 °F or >38 °C) with median onset on d + 2. Compared to patients who did not develop fevers, patients with fevers received higher median CD34+ cell dose (5.00 vs. 3.08 × 106/kg, p < 0.001), CD3+ cell dose (12.8 vs. 4.5 × 107/kg), were more likely to have received a myeloablative regimen (50% vs. 9%, p < 0.001), and PBSC source (71% vs. 9%, p < 0.001). Cox model showed that fever had no impact on TRM, GVHD, OS, and DFS. In the logistic regression to identify correlation with fevers, higher degree of HLA mismatches and use of PBSC were all predictors of developing fever. Fevers between infusion of the T-Cell replete graft and administration of PTCY are very common in Haplo-HSCT. This complication is transient and had no impact on post-transplant morbidity and mortality.

Steroid refractory acute graft-versus-host disease (SR aGvHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) has been used to treat SR aGvHD effectively and with low treatment related toxicity. In this study, we retrospectively analyzed the outcomes of 103 Steroid Refractory aGvHD (SR aGvHD) patients to identify factors associated with improved outcomes including the use of ECP. A total of 79 patients received ECP as part of their SR aGVHD treatment compared to 24 patients who did not. Both groups had similar aGVHD grade and maximum organ stage at onset of aGVHD and treatment initiation. Patients in the group that received ECP had better OS (p = 0.01), DFS (p = 0.008), lower relapse (p = 0.05) and similar NRM compared to the group that did not receive ECP. Patients that received ECP treatment also had shorter hospital stays in the first 180 days after onset of SR aGvHD (20 vs. 38 days, p = 0.03). Multivariable analysis for OS indicated patient CMV status (CMV+ versus CMV–, HR 2.34, CI 1.16–4.69), regimen intensity (Myelo vs. non-Myeloablative, HR 0.39, CI 0.20–0.75), and the use of ECP (ECP vs. no ECP, HR 0.39, CI 0.20–0.75) were associated with OS. In summary, the use of ECP in the treatment of SR aGvHD results in improved overall survival secondary to lower relapse rates compared to other therapeutic modalities that do not incorporate ECP.

Allografting from HLA-haploidentical donors (HID) is being increasingly utilized worldwide for patients lacking a conventional matched donor. However, its efficacy in older patients with AML and MDS is unclear. We analyzed 127 consecutive allografts for AML/MDS patients aged ≥ 60 years at our center to compare outcomes using HID to those of contemporaneous transplants using matched sibling (MRD) or matched unrelated (MUD) donors. Patient characteristics were similar except HID transplants were more likely in non-white patients and were more commonly performed with reduced intensity conditioning and a marrow graft. For MRD, MUD and HID transplants respectively, 2-year estimates of non-relapse mortality (17, 23, and 9%), relapse (32, 34, and 33%), overall survival (OS) (62, 55, and 67%) and disease-free survival (DFS) (51, 43, and 58%) were not significantly different. Maximum cumulative incidences of grade 2–4 acute GVHD were not different (27, 37, 39%), but incidences of NIH grade moderate to severe (39, 35, 15%, p  = 0.028 MUD vs. HID, p  = 0.026 MRD vs. HID) and severe chronic GVHD (9, 12, 0%, p  = 0.030 MUD vs. HID, p  = 0.009 MRD vs. HID) were significantly higher in MRD and MUD than in HID transplants. On multivariable analysis, donor type was not a significant determinant of OS, DFS, TRM, or relapse. However, male gender and high/very high Disease Risk Index (DRI) were associated with significantly higher rates of relapse (HR 1.94, p  = 0.047 for male gender, HR 2.48, p  = 0.004 for high/very high DRI) and lower OS (HR 1.94, p  = 0.018 for male gender, HR 1.80, p  = 0.025 for high/very high DRI). HIDs are an acceptable alternative to matched donors in older patients with AML and MDS.