Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial.

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months.

Long-Term Follow-Up of the Prospective Randomized AATT Study (Autologous or Allogeneic Transplantation in Patients With Peripheral T-Cell Lymphoma).

JCO Primary analysis of the phase III randomized AATT study showed that younger patients with peripheral T-cell lymphoma (PTCL) consolidated with autologous or allogeneic transplantation (alloSCT) had similar event-free survival (EFS) and overall survival (OS). Seven-year EFS of patients randomly assigned to alloSCT was 38% (95% CI, 25 to 52) compared with 34% (95% CI, 22 to 47) for patients randomly assigned to autologous transplantation of hematopoietic stem cells (autoSCT); OS was 55% (95% CI, 41 to 69) and 61% (95% CI, 47 to 74). Among patients undergoing alloSCT (n = 26) or autoSCT (n = 41) on study, the cumulative progression/relapse rate was 8% (95% CI, 0 to 19) and 55% (95% CI, 35 to 74).

Autologous stem cell transplantation in T-cell/histiocyte-rich large B-cell lymphoma: EBMT Lymphoma Working Party study.

Although broadly used, consolidative autologous hematopoietic stem cell transplantation (auto-HCT) for relapsed/refractory (R/R) T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) has never been specifically investigated. Here, we have analyzed outcomes of auto-HCT for THRLBCL compared with diffuse large cell B-cell lymphoma not otherwise specified (DLBCL). Eligible for this retrospective registry study were adult patients with R/R THRLBCL and DLBCL, respectively, who underwent a first auto-HCT in a salvage-sensitive disease status as assessed by positron emission tomography-computed tomography between 2016 and 2021 and were registered with the European Society for Blood and Marrow Transplantation database.

Hematopoietic stem cell transplantation for DLBCL: a report from the European Society for Blood and Marrow Transplantation on more than 40,000 patients over 32 years.

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018.

Radiotherapy in younger patients with advanced aggressive B-cell lymphoma-long-term results from the phase 3 R-MegaCHOEP trial.

The role of consolidative radiotherapy (RT) for patients with aggressive B-cell lymphoma has not been fully elucidated. The R-MegaCHOEP trial investigated the use of high-dose chemotherapy and rituximab with subsequent autologous stem cell transplantations compared to conventional immunochemotherapy (R-CHOEP) for high-risk patients up to 60 years. The study protocol included RT for patients with bulky (maximum diameter ≥7.

Hematopoietic cell transplantation and cellular therapies in Europe 2022. CAR-T activity continues to grow; transplant activity has slowed: a report from the EBMT.

In 2022, 46,143 HCT (19,011 (41.2%) allogeneic and 27,132 (58.8%) autologous) in 41,854 patients were reported by 689 European centers.

Cytomegalovirus immunoglobulin serology prevalence in patients with newly diagnosed multiple myeloma treated within the GMMG-MM5 phase III trial.

Objectives: The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown.

Methods: Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months.

Axicabtagene Ciloleucel versus Tisagenlecleucel for Relapsed or Refractory Large B Cell Lymphoma: A Systematic Review and Meta-Analysis.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor T cell (CAR-T) therapies approved for relapsed/refractory aggressive large B cell lymphoma (LBCL). Significant costs and complex manufacturing underscore the importance of evidence-based counseling regarding the outcomes of these treatments. With the aim of examining the efficacy and safety of axi-cel versus tisa-cel in patients with relapsed/refractory aggressive LBCL, we performed a systematic literature search of comparative studies evaluating outcomes in relapsed/refractory aggressive LBCL after treatment with axi-cel or tisa-cel.

CD19-directed CAR T cells as first salvage therapy for large B-cell lymphoma: towards a rational approach.

The approval of CD19-directed chimeric antigen receptor (CAR) T-cell therapies for the second-line treatment of high-risk large B-cell lymphoma (LBCL) has greatly affected salvage algorithms for this condition, and such therapies could have the potential to improve the course of relapsed or refractory LBCL. In this Review, we provide guidance for a rational management approach to the use of commercial CD19-directed CAR T cells in the second-line treatment of LBCL, addressing crucial questions regarding eligible histologies; age, comorbidity, and tumour biology restrictions; the handling of very aggressive tumour behaviour; and holding and bridging therapies. The guidance was developed in a structured manner and, for each question, consists of a description of the clinical issue, a summary of the evidence, the rationale for a practical management approach, and recommendations.

Organ complications after CD19 CAR T-cell therapy for large B cell lymphoma: a retrospective study from the EBMT transplant complications and lymphoma working party.

We investigated ≥ grade 3 (CTC-AE) organ toxicities for commercial CD19 chimeric antigen receptor T cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell Lymphoma in the European Society for Blood and Marrow Transplantation (EBMT) CAR-T registry. The incidence of ≥ grade 3 organ toxicities during the first 100 days after CAR-T was low and the most frequent were: renal (3.0%), cardiac (2.

The addition of rituximab to chemotherapy improves overall survival in mantle cell lymphoma-a pooled trials analysis.

Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma and commonly used induction immunochemotherapies include the anti-CD20 antibody rituximab. However, efficacy data for rituximab regarding overall survival (OS) in first line MCL therapy remain conflicting.We report long-term outcomes of a pooled trials analysis comparing Cyclophosphamide, Doxorubicine, Vincristine, Prednisone (CHOP) to R-CHOP in MCL to confirm efficacy on failure free survival (FFS) and OS in relevant subgroups.

Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study.

UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18-60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation.

Radiation and Dose-densification of R-CHOP in Primary Mediastinal B-cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial.

UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans.

Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT.

We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study).

Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party.

We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22.

Practice harmonization workshops of EBMT: an expert-based approach to generate practical and contemporary guidelines within the arena of hematopoietic cell transplantation and cellular therapy.

For hematopoietic cell transplantation (HCT) and cellular therapy (CT), clinical patient care is localized, and practices may differ between countries and from center to center even within the same country. Historically, international guidelines were not always adapted to the changing daily clinical practice and practical topics there were not always addressed. In the absence of well-established guidelines, centers tended to develop local procedures/policies, frequently with limited communication with other centers.

Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey.

In 2021, 47,412 HCT (19,806 (42%) allogeneic and 27,606 (58%) autologous) in 43,109 patients were reported by 694 European centers. 3494 patients received advanced cellular therapies, 2524 of which were CAR-T treatments, an additional 3245 received DLI. Changes compared to the previous year were CAR-T treatment (+35%), allogeneic HCT +5.