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PURPOSE: We sought to compare the pharmacokinetics (PKs) of DRL-rituximab (DRL_RI; potential biosimilar) and innovator rituximab MabThera (Roche, Grenzach-Wyhlen, Germany; reference medicinal product [RMP]) in patients with diffuse large B-cell lymphoma (DLBCL). Efficacy, pharmacodynamics (PDs), safety, and immunogenicity were also compared. PATIENTS AND METHODS: We conducted a double-blind, parallel-group study in patients with untreated DLBCL who were eligible to receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Patients were randomly assigned at a one-to-one ratio to receive DRL_RI or RMP for six 21-day cycles of rituximab plus CHOP, with 18 months of follow-up after day 1, cycle 6 (C6). Primary end point was C1 PKs, measured as area under the plasma concentration–time curve from day 0 to 21 (AUC0-21 days) and maximum plasma concentration (Cmax). Equivalence was defined as 90% CIs for the DRL_RI/RMP geometric mean ratios (GMRs) within 80% and 125%. Secondary end points included efficacy noninferiority measured by objective response rate (ORR) at C6 and event-free survival and overall survival at 87 weeks, PK equivalence at C6 and PD equivalence (rate of B-cell depletion and repletion), safety, and immunogenicity. The trial was stopped after sufficient patients for primary end point evaluation were enrolled. Secondary end points are reported as observed. RESULTS: A total of 151 patients were randomly assigned (DRL_RI, n = 76; RMP, n = 75). DRL_RI/RMP GMRs for AUC0-21 days and Cmax in C1 were 99.77 (90% CI, 87.60 to 113.63) and 96.19 (90% CI, 88.65 to 104.38), respectively. ORR at C6 for DRL_RI and RMP were 82.0% and 84.8%, respectively. Rates of B-cell depletion/repletion, immunogenicity, and adverse events were comparable in both groups. CONCLUSION: DRL_RI and RMP had equivalent PKs, with comparable efficacy, PDs, safety, and immunogenicity.

Introduction: Prediction of outcomes following allogeneic hematopoietic cell transplantation (HCT) remains a major challenge. Machine learning (ML) is a computational procedure that may facilitate the generation of HCT prediction models. We sought to investigate the prognostic potential of multiple ML algorithms when applied to a large single-center allogeneic HCT database. Methods: Our registry included 2,697 patients that underwent allogeneic HCT from January 1976 to December 2017. 45 pretransplant baseline variables were included in the predictive assessment of each ML algorithm on overall survival (OS) as determined by area under the curve (AUC). Pretransplant variables used in the EBMT ML study (Shouval et al., 2015) were used as a benchmark for comparison. Results: On the entire dataset, the random forest (RF) algorithm performed best (AUC 0.71 ± 0.04) compared to the second-best model, logistic regression (LR) (AUC = 0.69 ± 0.04) (p < 0.001). Both algorithms demonstrated improved AUC scores using all 45 variables compared to the limited variables examined by the EBMT study. Survival at 100 days post-HCT using RF on the full dataset discriminated patients into different prognostic groups with different 2-year OS (p < 0.0001). We then examined the ML methods that allow for significant individual variable identification, including LR and RF, and identified matched related donors (HR = 0.49, p < 0.0001), increasing TBI dose (HR = 1.60, p = 0.006), increasing recipient age (HR = 1.92, p < 0.0001), higher baseline Hb (HR = 0.59, p = 0.0002), and increased baseline FEV1 (HR = 0.73, p = 0.02), among others. Conclusion: The application of multiple ML techniques on single-center allogeneic HCT databases warrants further investigation and may provide a useful tool to identify variables with prognostic potential. [ABSTRACT FROM AUTHOR]

Context: Relative risk of non-Hodgkin lymphoma (NHL) in people living with HIV is 60–200 times that of normal population. This is the largest series from India on lymphomas arising in HIV-infected individuals including workup for Epstein–Barr virus (EBV) and human herpesvirus-8 (HHV-8). Aims: This study aims to ascertain the distribution and detailed clinicopathologic features of lymphoma arising in HIV-infected persons in India. Settings and Design: The study was done during the period of 2007–2011 in the pathology department of a tertiary care center in South India. Subjects and Methods: All cases diagnosed as lymphoma in the department of pathology during the study period were identified, and patients with HIV positive by serology were included in the study. Clinical details were obtained from electronic records, slides were reviewed and tissue blocks retrieved, and immunohistochemistry for HHV-8 and in situ hybridization for EBV-encoded RNA was done. Statistical Analysis Used: Descriptive statistics were done using SPSS software. Kaplan–Meier curves were used to do survival analysis. Results: Of 3346 patients diagnosed with lymphoma, 73 (2%) were diagnosed to be positive for HIV. About 87.6% of the cases were NHL, of which diffuse large B-cell lymphoma was the most common and plasmablastic lymphoma was the second common subtype. Survival was uniformly poor in 36% of the cases where follow-up was available. Conclusions: The striking differences from world literature included higher frequency of plasmablastic lymphomas, lack of primary central nervous system lymphomas, and low association with HHV8.

Allogeneic hematopoietic stem cell transplant (HSCT) and gene therapy (GT) are two potentially curative approaches for sickle cell disease (SCD), but they have never been compared in clinical trials. To compare the safety and efficacy of HSCT and GT to assist clinicians and patients in making informed treatment decisions. Phase I-III clinical trials and case reports/series were included. Regimens included HSCT from all stem cell sources, lentiviral gene therapy, and gene editing, with any conditioning regimen. We searched Medline and EMBASE databases as of 1st June 2020 for studies reporting HSCT and GT outcomes in SCD. The Newcastle-Ottawa scale was used to assess the risk of bias. Descriptive statistics and post-hoc imputation for standard deviations of mean change in FEV1 and FVC were performed. In total, 56 studies (HSCT, n = 53; GT, n = 3) representing 1,198 patients met inclusion criteria (HSCT, n = 1,158; GT, n = 40). Length of follow-up was 3,881.5 and 58.7 patient-years for HSCT and GT, respectively. Overall quality of evidence was low, with no randomized controlled trials identified. Two-year overall survival for HSCT was 91%; mortality was 2.5% for GT. Acute chest syndrome and vaso-occlusive episodes were reduced post-HSCT and GT. Meta-analysis was not possible due to lack of comparator and heterogeneity in outcome measures reporting. Very few studies reported post-transplant end-organ function. Six secondary malignancies (5 post-HSCT, 1 post-GT) were reported. Reporting of SCD-related complications and patient-important outcomes is lacking for both strategies. We advocate for standardized reporting to better compare outcomes within and between treatment groups. [ABSTRACT FROM AUTHOR]

Haploidentical stem cell transplantation (haploSCT) has greatly improved access to curative treatment for myeloid malignancies in patients without suitable matched sibling/unrelated donors. We investigated the safety and efficacy of haploSCT after reduced intensity conditioning (RIC) with anti-thymocyte globulin (ATG), post-transplant cyclophosphamide (PTCy), and cyclosporine to prevent rejection and graft-versus-host disease (GVHD). In this study, 47 patients received RIC using fludarabine, busulfan, and total body irradiation (200 cGy). Unmanipulated peripheral blood grafts were used. GVHD prophylaxis included ATG (4.5 mg/kg day−3 to −1), PTCy (50 mg/kg/day day +3, +4), and cyclosporine from day +5. The median follow-up was 15 months (range 3–27). Thirty one (66%) patients had acute myeloid leukemia (AML), 10 (21%) had high-risk myelodysplastic syndrome, and 6 (13%) had a myeloproliferative neoplasia. Median age was 60 years (range 22–73). The d+100 cumulative incidences of grade II–IV and III–IV acute GVHD were 17% (95% confidence interval (CI) 7.9–29.1) and 6.4% (1.6–15.9), respectively. The cumulative incidence of moderate-severe chronic GVHD at 1 year was 15.2% (95% CI 6.5–27.1). Overall survival (OS) and relapse-free survival (RFS) were 55.2% (95% CI 39.5–68.4) and 49.5% (95% CI 34.2–63), respectively. Nonrelapse mortality (NRM) for all patients at 1 year was 37.1% (95% CI 23.2–51.1). Infection was the main cause of death (26%). For AML, 1-year OS, RFS, and NRM were 64.1% (95% CI 43.3–78.9), 54.5 (95% CI 34.6–70.7), and 26.8% (95% CI 12.3–43.6), respectively. In conclusion, unmanipulated haploidentical peripheral blood stem cells (PBSC) transplantation following RIC and dual in vivo T-cell depletion results in a low incidence of acute and chronic GVHD for patients diagnosed with myeloid malignancies.