French early nationwide idecabtagene vicleucel chimeric antigen receptor T-cell therapy experience in patients with relapsed/refractory multiple myeloma (FENIX): A real-world IFM study from the DESCAR-T registry.

Idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real-world registry-based multicentre observational study in 11 French hospitals to evaluate ide-cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR-T registry. Of these, 159 patients (90%) received ide-cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression-free survival (PFS) from the ide-cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra-medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA-targeted immunoconjugate or T-cell-redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide-cel's feasibility, safety and efficacy in real-life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection.

Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA).

BACKGROUND: Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future. DESIGN: The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field. RESULTS: Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues. CONCLUSIONS: We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.

Postremission Consolidation by Autologous Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia in First Complete Remission (CR) and Negative Implications for Subsequent Allogeneic HCT in Second CR: A Study by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

After autologous hematopoietic cell transplantation (HCT) in the first complete remission (CR1), patients with acute myeloid leukemia (AML) may relapse and undergo allogeneic HCT in the second complete remission (CR2). The aim of this study was to analyze the outcome of allogeneic HCT performed in CR2 comparing patients with prior consolidation by autologous HCT versus patients with chemotherapy consolidation. Included were 2619 adults with allogeneic HCT in CR2 from 2000 to 2017 with (n = 417) or without (n = 2202) prior autologous HCT. Patient groups were not entirely comparable; patients with prior autologous HCT were younger, had less often a favorable cytogenetic profile, had more commonly donors other than matched siblings, and more often received reduced-intensity conditioning. In multivariate analysis, nonrelapse mortality risks in patients with prior autologous HCT were 1.34 (1.07 to 1.67; P = .01) after adjustment for age, cytogenetic risk, transplant year, donor, conditioning intensity, sex matching, interval diagnosis-relapse, and relapse-allogeneic HCT as compared with chemotherapy consolidation. Similarly, risks of events in leukemia-free survival and graft-versus-host disease, relapse-free survival were higher with prior autologous HCT, 1.17 (1.01 to 1.35), P = .03 and 1.18 (1.03 to 1.35), P = .02, respectively. Risk of death was also higher, 1.13 (0.97 to 1.32), P = .1, but this was not significant. Postremission consolidation with autologous HCT for AML in CR1 increases toxicity of subsequent allogeneic HCT in CR2.

Reduced-intensity versus reduced-toxicity myeloablative fludarabine/busulfan-based conditioning regimens for allografted non-Hodgkin lymphoma adult patients: a retrospective study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

BACKGROUND: Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet. PATIENTS AND METHODS: This was a retrospective with the aim to compare the outcomes of NHL patients who received before allo-SCT a fludarabine/busulfan conditioning regimen, either of reduced intensity (FB2, 2 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 277) or at a myeloablative reduced-toxicity dose (FB3/FB4, 3 or 4 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 101). RESULTS: In univariate analysis, the 2-year overall survival (FB2 66.5% versus 60.3%, P = 0.33), lymphoma-free survival (FB2 57.9% versus 49.8%, P = 0.26), and non-relapse mortality (FB2 19% versus 21.1%, P = 0.91) were similar between both groups. Cumulative incidence of grade III-IV acute graft versus host disease (GVHD) (FB2 11.2% versus 18%, P = 0.08), extensive chronic GVHD (FB2: 17.3% versus 10.7%, P = 0.18) and 2-year GVHD free-relapse free survival (FB2: 44.4% versus 42.8%, P = 0.38) were also comparable. In multivariate analysis there was a trend for a worse outcome using FB3/FB4 regimens (overall survival: HR 1.47, 95% CI: 0.96-2.24, P = 0.08; lymphoma-free survival: HR: 1.43, 95% CI: 0.99-2.06, P = 0.05; relapse incidence: HR 1.54; 95% CI: 0.96-2.48, P = 0.07). These results were confirmed using a propensity score-matching strategy. CONCLUSION: We conclude that reduced toxicity myeloablative conditioning with fludarabine/busulfan does not improve the outcomes compared with reduced-intensity conditioning in adults receiving allo-SCT for NHL.

Reduced intensity allogeneic stem cell transplantation for follicular lymphoma relapsing after an autologous transplant achieves durable long-term disease control: an analysis from the Lymphoma Working Party of the EBMT†.

BACKGROUND: Patients with follicular lymphoma (FL) relapsing after an autologous transplant (autoSCT) may be treated with a variety of therapies, including a reduced intensity allogeneic transplant (RICalloSCT). We conducted a retrospective analysis of a large cohort of patients undergoing RICalloSCT for FL in this setting. PATIENTS AND METHODS: A total of 183 patients, median age 45 years (range 21-69), had undergone an autoSCT at a median of 30 months before the RICalloSCT. Before the RICalloSCT, they had received a median of four lines (range 3-10) of therapy and 81% of patients had chemosensitive disease and 16% had chemoresistant disease. Grafts were donated from sibling (47%) or unrelated donors (53%). RESULTS: With a median follow-up of 59 months, the non-relapse mortality (NRM) was 27% at 2 years. The median remission duration post-autoSCT and RICalloSCT was 14 and 43 months, respectively. The 5-year relapse/progression rate, progression-free survival and overall survival were 16%, 48% and 51%, respectively, and were associated with age and disease status at RICalloSCT. CONCLUSION: These data suggest that an RICalloSCT is an effective salvage strategy in patients with FL recurring after a prior autoSCT and might overcome the poor prognostic impact of early relapse after autoSCT.

[SFGM-TC recommendation on indications for allogeneic stem cell transplantation in children with congenital neutropenia]. / Indications d'allogreffe dans les neutropénies constitutionnelles : recommandation de la SFGM-TC.

In this report, we address the issue of allogeneic stem cell transplantation in children with congenital neutropenia. Constitutional disorders with neutropenia are exceptional. Treatment and prevention of severe infections are a major concern in the management of chronic neutropenia. These disorders, especially Kostmann's disease and Shwachman-Bodian-Diamond syndrome, are associated with an increased risk of leukemia. The role of allogeneic stem cell transplantation in these patients is still unclear. In an effort to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille.

[The impact of donor naive and memory T cell subsets on patient outcome following allogeneic stem cell transplantation: relationship between infused donor CD4+/CCR7+ T cell subsets and acute graft-versus-host disease]. / Impact de la composition du greffon sur le devenir des patients après une allogreffe de cellules souches hématopoïétiques: corrélation entre proportion des lymphocytes T CD4+ du greffon exprimant le CCR7 et la survenue d'une GVH aiguë

In a previous prospective study on 62 patients who underwent an HLA-matched allogeneic stem cell transplantation, we have observed that proportion of donor-derived CCR7(+)/CD4(+) T cells in the graft provided a predictive indicator of acute GVHD without interfering on chronic GVHD and relapse rate. Here we present our results on a confirmatory cohort of 137 consecutive patients. Indeed patients who received more than 76% of CCR7(+)/CD4(+) T cells in the graft developed more often acute GVHD be it of low or high grade than those who did not. Determination of the CCR7(+)/CCR7(neg) ratio of CD4(+) T cells in the graft provides a predictive indicator of acute GVHD and could help to define strategies of partial selective T cell depleted transplantation.

[Conservation and destruction of autologous and allogeneic cryopreserved cellular products: recommendations from the SFGM-TC]. / Modalités de conservation et de destruction des produits cellulaires cryopréservés : recommandations de la SFGM-TC.

Thousands of autologous and at less extent allogeneic hematopoietic stem cells (HSC) bags are cryopreserved in France. The majority of autologous HSC grafts are used within a year after collection. However, many bags are still unused and cryopreserved for many years. In France and on a European scale, the ever-growing number of cryopreserved bags represents a real economic health concern. Indeed, the cost of storage is about 100€ per bag and per year. In addition, quality and therapeutic value of these long-term cryopreserved grafts needs to be evaluated. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from its member centers across France. These workshops took place in September 2013 in Lille. In this article, we addressed the issue of the destruction of long-term cryopreserved grafts be them autologous or allogeneic and provide recommendations regarding their destruction.

[Utilisation of immunosuppressants in the prevention of a graft versus host reaction: report by the SFGM-TC]. / Immunosuppresseurs dans la prévention de la réaction du greffon contre l'hôte : rapport de la SFGM-TC.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here we report our recommendations regarding the use of immunosuppressive treatment in the prevention of graft versus host disease: report by the SFGM-TC.

[Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC]. / Autogreffe des cellules souches hématopoïétiques dans les maladies auto-immunes : recommandations de la SFGM-TC.

Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients.

[Impact of anti-HLA antibodies on outcomes of allogeneic stem cell transplantation: a report by the SFGM-TC]. / Impact des anticorps anti-HLA sur le devenir de l'allogreffe de cellules souches hématopoïétiques : un rapport par la SFGM-TC.

The role of anti-HLA antibodies in allogeneic stem cell transplantation setting is still unclear. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This article offers the recommendations of the group that considered the impact that have anti-HLA antibodies on outcomes in allogeneic stem cell transplantation.

[Managing late-effects after allogeneic stem cell transplantation in children: recommendations from the SFGM-TC]. / Prise en charge des séquelles après greffe de cellules souches hématopoïétiques chez l'enfant : recommandations de la SFGM-TC.

In this report, we address the issue of late-effects after allogeneic stem cell transplantation in children. In an effort to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille.

[Transfer of skills: implementing post-transplant follow-up care status for transplant nurses: a report by the SFGM-TC]. / Transfert de compétence : la mise en place d'un statut infirmier(ère) de greffe pour le suivi post-greffe : un rapport par la SFGM-TC.

The number of Hematopoietic Stem Cell Transplantations has globally taken off in the past decade. However, this increase in transplantation activity has put in the spotlight the need to create a special transplantation-skilled population of nurses. This type of specialisation allocated solely to this activity has not existed within the French nursing community until now. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) sets up its forth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here we report our results and recommendations regarding the implementation of a transplant nurse status for post-transplant follow-up care.

Quality controls on cord blood unit contiguous segments: recommendation of the SFGM-TC.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. Literature and intra-laboratories studies suggest that attached segment is representative of cord blood unit (CBU). Nevertheless, some discrepancies have been observed when analyzing large data registries. To address these issues, we have listed recommendations to increase the standardization of segment processing and quality control (QC), information on units of measurement and specifications and action to be taken in case of out of specifications QC results on segment.

[Allogeneic stem cell transplantation from an HLA-haploidentical related donor: SFGM-TC recommendations (Part 1)]. / Greffes de cellules souches hématopoïétiques à partir d'un donneur haplo-identique : recommandations de la SFGM-TC (première partie).

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part one of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.

[Allogeneic stem cell transplantation from an HLA-haploidentical related donor: SFGM-TC recommendations (part 2)]. / Greffes de cellules souches hématopoïétiques à partir d'un donneur haploidentique : recommandations de la SFGM-TC (deuxième partie).

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part two of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.

[Prophylactic, preemptive and curative use of donor lymphocyte infusion in patients undergoing allogeneic stem cell transplantation: guidelines of the SFGM-TC]. / Recommandations de la SFGM-TC concernant l'injection prophylactique, préemptive et curative des lymphocytes du donneur (DLI) après allogreffe de cellules souches hématopoïétiques.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here, we report our recommendations regarding the use of donor lymphocyte injection (DLI) in the prophylactic, pre-emptive and curative settings. This work has been limited to allogeneic stem cell transplantations from an HLA-matched (10/10) or -one antigen-mismatched (9/10) donor.

Allogeneic hematopoietic cell transplantation is equally effective in secondary acute lymphoblastic leukemia (ALL) compared to de-novo ALL-a report from the EBMT registry.

Secondary acute lymphoblastic leukemia (s-ALL) comprises up to 10% of ALL patients. However, data regarding s-ALL outcomes is limited. To answer what is the role of allogeneic hematopoietic cell transplantation (HCT) in s-ALL, a matched-pair analysis in a 1:2 ratio was conducted to compare outcomes between s-ALL and de novo ALL (dn-ALL) patients reported between 2000-2021 to the European Society for Blood and Marrow Transplantation registry. Among 9720 ALL patients, 351 (3.6%) were s-ALL, of which 80 were in first complete remission (CR1) with a known precedent primary diagnosis 58.8% solid tumor (ST), 41.2% hematological diseases (HD). The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between ST and HD patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL. To conclude, patients with s-ALL who received HCT in CR1 have comparable outcomes to patients with dn-ALL.

Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT.

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.

Artificial intelligence methods to estimate overall mortality and non-relapse mortality following allogeneic HCT in the modern era: an EBMT-TCWP study.

Allogeneic haematopoietic cell transplantation (alloHCT) has curative potential counterbalanced by its toxicity. Prognostic scores fail to include current era patients and alternative donors. We examined adult patients from the EBMT registry who underwent alloHCT between 2010 and 2019 for oncohaematological disease. Our primary objective was to develop a new prognostic score for overall mortality (OM), with a secondary objective of predicting non-relapse mortality (NRM) using the OM score. AI techniques were employed. The model for OM was trained, optimized, and validated using 70%, 15%, and 15% of the data set, respectively. The top models, "gradient boosting" for OM (AUC = 0.64) and "elasticnet" for NRM (AUC = 0.62), were selected. The analysis included 33,927 patients. In the final prognostic model, patients with the lowest score had a 2-year OM and NRM of 18 and 13%, respectively, while those with the highest score had a 2-year OM and NRM of 82 and 93%, respectively. The results were consistent in the subset of the haploidentical cohort (n = 4386). Our score effectively stratifies the risk of OM and NRM in the current era but do not significantly improve mortality prediction. Future prognostic scores can benefit from identifying biological or dynamic markers post alloHCT.