S. Rives

Bio: S. Rives is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Medicine & Internal medicine. The author has an hindex of 2, co-authored 2 publications receiving 2046 citations.

Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

Abstract: Background In a single-center phase 1–2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) Methods We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months Results For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry The rates of event-f

Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial

Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In the primary analysis of the global phase II ELIANA trial (ClinicalTrials.gov identifier: NCT02435849), tisagenlecleucel provided an overall remission rate of 81% in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), with 59% of responders remaining relapse-free at 12 months. Here, we report an update on efficacy, safety, and patient-reported quality of life in 79 pediatric and young adult patients with R/R B-ALL following a median follow-up of 38.8 months. The overall remission rate was 82%. The median event-free survival was 24 months, and the median overall survival was not reached. Event-free survival was 44% (95% CI, 31 to 57) and overall survival was 63% (95% CI, 51 to 73) at 3 years overall (most events occur within the first 2 years). The estimated 3-year relapse-free survival with and without censoring for subsequent therapy was 52% (95% CI, 37 to 66) and 48% (95% CI, 34 to 60), respectively. No new or unexpected long-term adverse events were reported. Grade 3/4 adverse events were reported in 29% of patients > 1 year after infusion; grade 3/4 infection rate did not increase > 1 year after infusion. Patients reported improvements in quality of life up to 36 months after infusion. These findings demonstrate favorable long-term safety and suggest tisagenlecleucel as a curative treatment option for heavily pretreated pediatric and young adult patients with R/R B-ALL.

S112: tisagenlecleucel in pediatric and young adult patients (pts) with relapsed/refractory (r/r) b-cell acute lymphoblastic leukemia (b-all): final analyses from the eliana study

Abstract: Background: Pediatric and young adult pts with R/R B-ALL experience a treatment journey characterized by diminishing likelihood of cure and increasing morbidity. Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for use in pediatric and young adults with B-ALL and adults with B-cell lymphomas. Tisagenlecleucel provided high rates of remission (>80%) in children and young adults with R/R B-ALL in ELIANA, with 62% of responders remaining relapse-free at 24 mo (Grupp et al, Blood, 2018). Aims: Here, we report the final efficacy and safety analyses in pts followed up to 5.9 years post-tisagenlecleucel infusion. Methods: ELIANA (NCT02435849) was a pivotal, Phase II, open-label, multicenter, global study of tisagenlecleucel in pediatric and young adult pts with R/R B-ALL. Pts received a single infusion of tisagenlecleucel at 0.2-5.0×106 CAR+ viable T cells/kg body weight for pts ≤50 kg and 0.1-2.5×108 CAR+ viable T cells for pts >50 kg. Endpoints included overall remission rate (ORR) within 3 mo, relapse-free survival (RFS), duration of remission (DOR), overall survival (OS), persistence of B-cell aplasia, and short- and long-term safety events. Results:Results: As of September 24, 2021, 97 pts were enrolled and 79 pts (81%) received tisagenlecleucel. Median time from infusion to data cutoff was 5.5 y; 64 pts had ≥5 y of follow-up. At study entry, the median age was 11 y (range, 3-24). Pts were heavily pretreated with a median of 3 prior lines of therapy (range, 1-8) and 61% had a history of prior stem cell transplant (SCT). ORR (complete remission [CR] or CR with incomplete hematologic recovery within 3 mo after infusion) was 82% (95% CI, 72-90). Among pts in remission (CR/CRi), the 5y RFS rate was 49% (95% CI, 34-62), and the median RFS was not reached (Figure, 46.8 mo when censoring for SCT; n=15). The median time to B-cell recovery was 38.6 mo (95% CI, 23-not reached) and the probability of B-cell aplasia at 6 mo and 12 mo was 83% (95% CI, 71-91) and 71% (95% CI, 57-82), respectively. Pts with B-cell recovery (<6 mo, n=10; 6-12 mo, n=4; >12 mo, n=7) experienced a 2y cumulative incidence of relapse of 25.2% (with SCT treated as a competing risk). Among all pts, the 5y EFS and OS rates were 42% (95%CI, 29-54) and 55% (95% CI, 43-66), respectively. There were no significant differences in any efficacy endpoint between pediatric (<18 y; n=65) and young adult (≥18 y; n=14) pts. No new or unexpected AEs were reported during long-term follow-up. Among pts in remission, the most commonly reported grade ≥3 AEs occurring >1 y post-infusion were infection (20%) and cytopenias (6%). Ten (14%) pts in remission experienced long-term cytopenias persisting for >1 y; however, none of these pts experienced cytopenias persisting for >5 y (median 2 y; range, 1.1-5y). Eighty-two percent of pts received IVIG any time post-infusion. Image:Summary/Conclusion: This >5 y follow-up study demonstrates continued durable efficacy of tisagenlecleucel without late adverse effects in heavily pretreated pediatric and young adult pts with R/R B-ALL. Tisagenlecleucel continues to be a potentially curative treatment option for pediatric and young adult patients with R/R B-ALL.

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Abstract: Background Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. Methods We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. Results A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 ...

CAR T cell immunotherapy for human cancer

Abstract: Adoptive T cell transfer (ACT) is a new area of transfusion medicine involving the infusion of lymphocytes to mediate antitumor, antiviral, or anti-inflammatory effects. The field has rapidly advanced from a promising form of immuno-oncology in preclinical models to the recent commercial approvals of chimeric antigen receptor (CAR) T cells to treat leukemia and lymphoma. This Review describes opportunities and challenges for entering mainstream oncology that presently face the CAR T field, with a focus on the challenges that have emerged over the past several years.

Chimeric Antigen Receptor Therapy.

Abstract: Chimeric Antigen Receptor T Cells This review addresses T-cell engineering and synthetic immunity, with a focus on producing durable remissions in patients with treatment-refractory tumors. Toxic e...

Delivery technologies for cancer immunotherapy

Abstract: Immunotherapy has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing, with numerous treatments in clinical and preclinical development. However, a key challenge in the broad implementation of immunotherapies for cancer remains the controlled modulation of the immune system, as these therapeutics have serious adverse effects including autoimmunity and nonspecific inflammation. Understanding how to increase the response rates to various classes of immunotherapy is key to improving efficacy and controlling these adverse effects. Advanced biomaterials and drug delivery systems, such as nanoparticles and the use of T cells to deliver therapies, could effectively harness immunotherapies and improve their potency while reducing toxic side effects. Here, we discuss these research advances, as well as the opportunities and challenges for integrating delivery technologies into cancer immunotherapy, and we critically analyse the outlook for these emerging areas.