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Introduction: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent‐behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. Methods: Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Patients who received induction with high‐dose cytarabine and/or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy (n = 88) while all other approaches were non‐intensive (n = 131). Results: There was no difference in progression‐free (PFS; P =.224) or overall survival (OS; P =.167) in deferred patients who received non‐intensive vs. intensive therapy. Additionally, univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Treatment at an academic center (HR 0.43, P =.015) was associated with improved OS in both univariate and multivariate models, while intensity of treatment was not associated with improved OS in either model. Conclusions: These results indicate that intensified initial treatment is not associated with improved survival after deferring initial therapy, although prospective studies are needed to determine which of these patients with MCL may benefit from intensive therapy. [ABSTRACT FROM AUTHOR]

A proportion of patients with diffuse large B cell lymphoma (DLBCL) will fail to achieve durable remission to standard chemoimmunotherapy treatment with R-CHOP or dose- adjusted R-EPOCH regimens [1]. This benefit may be offset by an increased rate of relapse, however, leading to no significant differences in overall survival (OS) between patients receiving myeloablative conditioning (MAC) regimens and those receiving RIC regimens. 333, 1995, 1540-1545 3 E. Van Den Neste, N. Schmitz, N. Mounier, Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study. [Extracted from the article]

Background: Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT.Methods: PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphoma and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician, and met at least one prespecified transplantation not intended criterion. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 days) followed 2-7 days later by two sequential lisocabtagene maraleucel infusions (equal target doses of CD8+ and CD4+ CAR+ T cells for a total target dose of 100 × 106 CAR+ T cells). The primary endpoint was the overall response rate and was assessed in all patients who received lisocabtagene maraleucel and had confirmed PET-positive disease before lisocabtagene maraleucel administration based on an independent review committee according to the Lugano 2014 criteria. Safety was assessed in all patients who received lisocabtagene maraleucel. Patient follow-up is ongoing. This study is registered with ClinicalTrials.gov, NCT03483103.Findings: Between July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70-78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR 6·1-18·0). 49 (80% [95% CI 68-89]; p<0·0001) patients had an overall response. The most common grade 3 or worse treatment-emergent adverse events were neutropenia (29 [48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths.Interpretation: These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended.Funding: Juno Therapeutics, a Bristol-Myers Squibb company. [ABSTRACT FROM AUTHOR]

• Bloodless autologous hematopoietic cell transplantation may be safely performed. • Prime hemoglobin with erythropoiesis-stimulating agents before transplant. • Thrombopoietin agonists may be considered to optimize transplant success. Bloodless autologous hematopoietic cell transplantation is associated with risks of severe bleeding and profound anemia. RBC or platelet transfusions are often used to prevent these hematologic complications. However, in patients such as Jehovah's Witnesses who refuse major blood components, the lack of transfusion support is not an absolute contraindication to an autologous hematopoietic cell transplant. Pennsylvania Hospital performed the world's first bloodless hematopoietic cell transplant more than 15 years ago and has gradually improved its technique with a sizable patient population. Erythropoiesis-stimulating agents were successfully employed as part of their pretransplant regimen to prevent severe anemia. Thrombopoietin agonists' potential role in bloodless transplant is also currently being explored. Although there is limited literature, available reports in combination with physiologic reasoning may support the use of these growth factors to promote transplant success. These agents offer potential benefit and may be of utility in minimizing complications of a bloodless transplant. In this review, we summarize the available literature and offer insight into how we may incorporate growth factors to allow bloodless autologous hematopoietic cell transplantation to be an available option to patients who may otherwise be denied. [ABSTRACT FROM AUTHOR]

Highlights • CYP3A5 polymorphisms did not impact i.v. tacrolimus exposure post-transplant. • CYP3A4 and ABCB1 polymorphisms impacted i.v. tacrolimus exposure post-transplant. • ABCB1 2677TT genotype was associated with increased risk of tacrolimus toxicity. • C YP3A4 and ABCB1 C2677T genotyping may help individualize i.v. tacrolimus dosing. • Pharmacogenomic guidelines should acknowledge differences in i.v. versus oral tacrolimus. Abstract Pharmacogenetics influences oral tacrolimus exposure; however, little data exist regarding i.v. tacrolimus. We investigated the impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on i.v. tacrolimus exposure and toxicity in adult patients receiving an allogeneic hematopoietic stem cell transplant for hematologic malignancies. Germline DNA was extracted from buccal swabs and genotyped for CYP3A4, CYP3A5, and ABCB1 polymorphisms. Continuous i.v. infusion of tacrolimus.03 mg/kg/day was initiated on day +5 post-transplant, and steady-state blood concentrations were measured 4days later. We evaluated the association between phenotypes and prevalence of nontherapeutic target concentrations (below or above 5 to 15 ng/mL) as well as tacrolimus-related toxicities. Of 63 patients, 28.6% achieved the target concentration; 71.4% were >15ng/mL, which was more common in CYP3A4 intermediate/normal metabolizers (compared with rapid) and those with at least 1 ABCB1 C2677T loss-of-function allele (P <.05). ABCB1 C2677T was significantly associated with concentrations >15ng/mL (odds ratio, 6.2; 95% confidence interval, 1.8 to 23.6; P =.004) and tacrolimus-related toxicities (odds ratio, 7.5; 95% confidence interval, 1.6 to 55.2; P =.02). ABCB1 C2677T and CYP3A4 are important determinants of i.v. tacrolimus exposure, whereas ABCB1 C2677T also impacts tacrolimus-related toxicities in stem cell transplants. [ABSTRACT FROM AUTHOR]

Background Autologous stem cell transplant (ASCT) is frequently used as a consolidative therapy option after induction treatment in fit patients with mantle cell lymphoma (MCL) with the goal of prolonging the initial response duration. Despite recent advances there remains a subset of patients who experience early disease relapse after ASCT. We examined predictors of shortened progression-free survival (PFS) and post-relapse overall survival (OS) in a cohort of patients completing ASCT in first remission. Methods We evaluated MCL patients treated at 10 US academic medical centers. Eligible patients were treated from 2000 through 2017, and we collected information on demographic, clinical, and treatment-related variables of interest. Patients were then categorized into three post-ASCT PFS groups: 0-2 years, 2-5 years, and > 5 years, with PFS determined from the date of ASCT until progression or death from any cause. Patients followed for at least 5 years post-ASCT who were relapse free were included in the > 5 sub group. Associations were examined between groups and collected characteristics using chi-squared tests for categorical patient characteristics and ANOVA for numeric patient characteristics. The Kaplan-Meier method was used to estimate overall survival (OS) for each group, using time of relapse after ASCT as the starting point. Results Of 968 total MCL patients, 242 patients completed ASCT in first remission and either had a PFS event or were relapse-free for at least 5 years post-ASCT. Patients were 80% male, and the median age was 59 (Range: 29-83). The patients were divided into groups of post-ASCT PFS 0-2 years (n=74), 2-5 years (n=75), and more than 5 years (n=93). Post-ASCT PFS was shorter in patients with stage 4 disease (p=0.022), splenomegaly at baseline (p=0.005), and a lymph node size > 5 centimeters at baseline (p=0.043). Other variables were not significantly associated with PFS, including time to transplant and use of intensive therapy. Patients with 0-2 year PFS had a shorter median OS (22.1 months, 95% CI: 13.1- 38.1 months) in comparison to 2-5 year PFS (132 months, 95% CI: 36-132 months) and 5+ year PFS not reached (95% CI: 41.2 – N.A; Figure). Conclusion Patients with higher tumor burden at baseline have a shorter post-ASCT PFS and are more likely to relapse within 2 years. As has been seen in other lymphoma subtypes, early relapse is associated with shorter OS. This represents a patient group requiring improved therapies and perhaps are the best candidates for post-ASCT maintenance or consolidation approaches. Further studies integrating minimal residual disease and molecular risk-stratification may better identify patients at high risk for early progression. [ABSTRACT FROM AUTHOR]