Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study
The Lancet Haematology, 2024 August; 11(8):e593–605
Single center, real-world retrospective study of CAR-T cell therapy for relapsed/ refractory large B-cell lymphoma beyond second line: five-year results at the University Hospitals Leuven
Acta Clinica Belgica, 2024 September 18; 79(4):276–84
Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume
Blood, 2024 June 13; 143(24):2464–73
Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma
Journal of Hematology and Oncology, 2024 August 6; 17(1):61
Optimizing the post-CAR T monitoring period for axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel
Blood Advances, 2024 October 22; 8(20):5346–54
Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma
Annals of Oncology, 2024 November; 35(11):1039–47
Risk of second tumors and T-cell lymphoma after CAR T-cell therapy
The New England Journal of Medicine, 2024 June 13; 390(22):2047–60 and more.....
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EPCORITAMAB MONOTHERAPY IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA (EPCORE NHL-1):
A PHASE 2 COHORT OF A SINGLE-ARM, MULTICENTRE STUDY
The Lancet Haematology, 2024 August; 11(8):e593–605
AUTHORS: Linton KM, Vitolo U, Jurczak W, Lugtenburg PJ, Gyan E, Sureda A, Christensen JH, Hess B, Tilly H, Cordoba R, Lewis DJ, Okada C, Hutchings M, Clausen MR, Sancho JM, Cochrane T, Leppä S, Chamuleau ME, Gernhardt D, AltıntaŞ I, Liu Y, Ahmadi T, Dinh MH, Hoehn D, Favaro E, Elliott B, Thieblemont C, Vose JM
CENTRE FOR CORRESPONDENCE: The Christie NHS Foundation Trust, Manchester Cancer Research Centre, and Division of Cancer Sciences, University of Manchester, Manchester, UK
BACKGROUND & AIM: Patients with multiply relapsed or refractory follicular lymphoma have poor outcomes and currently there is no standard treatment. Epcoritamab is a CD3 × CD20 bispecific antibody that induces T-cell-mediated cytotoxicity against malignant B cells. In phase 1 of the EPCORE NHL-1 trial, epcoritamab had promising activity in patients with relapsed or refractory follicular lymphoma. The aim of this paper was to report on the primary analysis of patients with relapsed or refractory follicular lymphoma who received epcoritamab after at least two previous lines of therapy in phase 2 of the EPCORE NHL-1 trial.
METHOD: The EPCORE NHL-1 trial is being conducted at 88 sites across 15 countries. Phase 2 included a pivotal (dose-expansion) cohort and a cycle-1 optimisation cohort. Participants were aged ≥18 years and had relapsed or refractory, CD20+, follicular lymphoma (grade 1–3A) and an Eastern Cooperative Oncology Group performance status ≤2. All had received at least two previous lines of therapy. Patients received epcoritamab,
48 mg subcutaneously, in 28-day cycles: weekly in cycles 1–3, biweekly in cycles 4–9, then every 4 weeks until disease progression or unacceptable toxicity. Step-up dosing regimens were used to reduce the risk and severity of CRS, with an additional intermediate dose and other ameliorating treatments introduced in the cycle-1 optimisation cohort.
RESULTS: The pivotal cohort included 128 patients (median age 65 years, 38% female) and the median follow-up time was 17.4 months. The overall response rate was 82.0%, with 62.5% of patients having a complete response. The most common grade-3 or -4 treatment-emergent adverse event was neutropenia (25% of patients). Grade-1 or -2 CRS was reported in 65% of patients and 2% had grade-3 CRS. In addition, grade-1 or -2 ICANS was reported in 6%. The cycle-1 optimisation cohort included 86 patients (median age 64 years, 43% female) and the median follow-up time was 5.7 months. The overall response rate was 86.0%, with 64.0% of patients having a complete response. The incidence of CRS was 49%, all of which was grade 1 or 2. There were no cases of ICANS.
CONCLUSIONS: In patients with relapsed or refractory CD20+ follicular lymphoma, epcoritamab was associated with an overall response rate over 80%. Cycle-1 optimisation improved safety.
https://doi.org/10.1016/S2352-3026(24)00166-2
LISOCABTAGENE MARALEUCEL IN FOLLICULAR LYMPHOMA:
THE PHASE 2 TRANSCEND FL STUDY
Nature Medicine, 2024 August; 30(8):2199–207
AUTHORS: Morschhauser F, Dahiya S, Palomba ML, et al.
CENTRE FOR CORRESPONDENCE: Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Centre Hospitalier Universitaire de Lille, Lille, France
BACKGROUND & AIM: In patients with relapsed or refractory follicular lymphoma, third-line or later treatment with chimeric antigen receptor (CAR) T-cell therapies produces responses but the optimal timing of treatment is unclear. Moreover, little is known about the use of CAR T-cell therapy as second-line treatment for patients with high-risk disease, such as progression within 24 months of first-line immunochemotherapy. Lisocabtagene maraleucel (lisocel), an autologous, CD19-directed, 4-1BB CAR T-cell product, has produced deep and durable responses in patients with relapsed or refractory large B-cell lymphoma. The aim of this study was to evaluate the efficacy and safety of liso-cel in patients with relapsed or refractory follicular lymphoma, including those undergoing second-line treatment.
STUDY DESIGN: Open-label single-arm phase-2 clinical study.
METHOD: This study, the TRANSCEND FL study, included 130 adults with relapsed or refractory follicular lymphoma who had received at least one prior line of therapy. Some had disease progression within 24 months of diagnosis after treatment with an anti-CD20 antibody and an alkylating agent. Patients underwent leukapheresis for liso-cel production. Treatment consisted of
intravenous fludarabine and cyclophosphamide followed after 2–7 days by a single liso-cel infusion (target dose: 100 × 106 CAR+ T cells).
RESULTS: Of the 130 patients, 23 received liso-cel as second-line treatment and 107 received it as third line or later treatment. Of these, 124 patients (23 on secondline treatment, 101 on third line or later treatment) were evaluable for efficacy. The median duration of follow-up was 18.9 months. In patients undergoing thirdline or later treatment, the overall response rate (assessed by independent review committee) was 97% (95% confidence interval 92−99%) and the complete response rate was 94% (95% CI 88−98%). In patients undergoing second-line treatment, the overall response rate was 96% (95% CI 78−100%) and all responses were complete responses. Grade-3 or higher treatmentemergent adverse events were experienced by 97 patients and 32 had serious treatment-emergent events. The most common grade-3 or higher events were cytopenias. Cytokine release syndrome developed in 58% of patients (grade ≥3 in 1%) and 15% had neurological events (grade ≥3 in 2%).
CONCLUSIONS: In patients with relapsed or refractory follicular lymphoma, including those with high-risk disease undergoing second-line treatment, lisocabtagene maraleucel was associated with high response rates. Adverse events were manageable.
https://doi.org/10.1038/s41591-024-02986-9
SINGLE CENTER, REAL-WORLD
RETROSPECTIVE STUDY OF CAR-T CELL THERAPY FOR RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA BEYOND SECOND LINE:
FIVE-YEAR RESULTS AT THE UNIVERSITY HOSPITALS LEUVEN
Acta Clinica Belgica, 2024 September 18; 79(4):276–84
AUTHORS: Brijs J, Van Ham J, Dubois B, Sinap F, Vergote V, Dierickx D, Vandenberghe P CENTRE: Department of Hematology, University Hospitals Leuven, Leuven, Belgium
BACKGROUND & AIM: Chimeric antigen receptor (CAR) T-cell therapy is a relatively new immunotherapy for relapsed or refractory large B-cell lymphoma (LBCL). In Belgium, the CAR T-cell products axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisacel) are both currently reimbursed for third or later lines of therapy in these patients. The aim of this study was to investigate the efficacy and safety of commercial CAR T-cell therapy as third-line or later treatment for patients with relapsed or refractory LBCL at a single institution.
STUDY DESIGN: Retrospective real-world cohort study.
METHOD: The study included 79 patients with relapsed or refractory LBCL who had previously received two lines of therapy. All underwent leukapheresis for CAR T-cell therapy at the University Hospitals Leuven between April 2019 and October 2023. Treatment responses were assessed by combined positron-emission and computed tomography 30, 60 (optional), 90, 180 and 360 days after CAR T-cell infusion and classified according to the 2014 Lugano criteria and assessment by treating physicians.
Overall survival after apheresis was also assessed in an intention-to-treat analysis.
RESULTS: Of the 79 patients, 11 (14%) did not progress to CAR T-cell infusion due to rapidly progressive disease or coronavirus disease 2019 (COVID-19). The median follow-up time after leukapheresis was 7.5 months in the 68 patients who underwent CAR T-cell infusion and 13.8 months in those who were still alive after infusion. The best overall response rate was 88% with axi-cel and 64% with tisa-cel (p=0.04). The corresponding complete response rates in the two treatment groups were 66% and 49%, respectively. The median duration of response was not reached for axi-cel and 9.8 months for tisa-cel. The 1-year progression-free and overall survival rates were 48% and 62%, respectively, with axicel and 30% and 43%, respectively, with tisa-cel. Any-grade CRS was reported in 97% and 82% of patients on axi-cel and tisa-cel, respectively, and any-grade ICANS was reported in 54% and 24% of patients on the two treatments, respectively. Nonrelapse mortality after infusion was 13%.
CONCLUSIONS: In patients with relapsed or refractory LBCL who had previously received two lines of treatment, CAR T-cell therapy was associated with high response rates and durable responses. Efficacy and toxicity tended to be higher with axicabtagene ciloleucel than tisagenlecleucel.
https://doi.org/10.1080/17843286.2024.2399365
AXICABTAGENE CILOLEUCEL VS STANDARD OF CARE IN SECOND-LINE LARGE B-CELL LYMPHOMA:
OUTCOMES BY METABOLIC TUMOR VOLUME
Blood, 2024 June 13; 143(24):2464–73
AUTHORS: Locke FL, Oluwole OO, Kuruvilla J, Thieblemont C, Morschhauser F, Salles G, Rowe SP, Vardhanabhuti S, Winters J, Filosto S, To C, Cheng P, Schupp M, Korn R, Kersten MJ CENTRE FOR CORRESPONDENCE: Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida, USA
BACKGROUND & AIM: The metabolic tumour volume (MTV), an indicator of tumour burden, is a promising prognostic indicator for patients with large B-cell lymphoma (LBCL). In those receiving antiCD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory LBCL after at least two lines of therapy, a high pretreatment MTV has been associated with poor clinical outcomes. The aim of this study was to determine whether whole body MTV at baseline is associated with clinical outcomes in patients with LBCL treated with CAR T-cell or standard therapy.
STUDY DESIGN: Analysis of data from the phase-3 ZUMA-7 study.
METHOD: The ZUMA-7 study included 359 adults with LBCL who had relapsed within 12 months of, or who were refractory to, first-line chemoimmunotherapy, 340 of whom had evaluable baseline MTV imaging measurements. Of the 340, 175 had been randomized to autologous anti-CD19 CAR T-cell therapy with axicabtagene ciloleucel (axi-cel), whereas 165 received standard care. Patients randomized to axi-cel underwent leukapheresis followed by lymphodepleting therapy prior to axi-cel infusion (target dose: 2 × 106 CAR T cells/kg). Standard care comprised 2–3 cycles of chemoimmunotherapy
followed by high-dose chemotherapy with autologous stem cell transplantation in patients who had a response. Outcomes in patients with a low MTV (i.e. less than or equal to the median value) and those with a high MTV (i.e. more than the median value) were compared. The median duration of follow-up was 24.9 months.
RESULTS: In the axi-cel arm, patients with a high MTV had shorter event-free survival compared to those with a low MTV. Similarly, in patients receiving standard care, event-free survival was shorter for a high versus a low MTV. In addition, progressionfree survival was also shorter for a high MTV in both axi-cel and standard-care arms. Patients with an ongoing response at data cut-off had a lower median MTV than those without. Among patients on axi-cel, those who experienced a grade-3 or higher neurological event or developed cytokine release syndrome had a higher median MTV than those who had grade-1 or -2 adverse events or no neurological event or cytokine release syndrome.
CONCLUSIONS: In patients with relapsed or refractory LBCL, a low baseline metabolic tumour volume was associated with longer event-free and progression-free survival compared with a high volume, whether patients were receiving CAR T-cell or standard therapy. In patients on CAR T-cell therapy, a high tumour volume was associated with more severe adverse events.
https://doi.org/10.1182/blood.2023021620
NOVEL PROGNOSTIC SCORING SYSTEMS FOR SEVERE CRS AND ICANS AFTER ANTI-CD19 CAR T CELLS IN LARGE B-CELL
LYMPHOMA
Journal of Hematology and Oncology, 2024 August 6; 17(1):61
AUTHORS: Sesques P, Kirkwood AA, Kwon M, et al.
CENTRE FOR CORRESPONDENCE: Hematology Department, Hospices Civils de Lyon, Lyon, France
BACKGROUND & AIMS: Treatment with chimeric antigen receptor (CAR) T cells directed against the CD19 antigen can improve the prognosis of patients with relapsed or refractory large B-cell lymphoma (LBCL). However, this treatment can cause severe early toxicities, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can be lifethreatening. The aims of this study were to evaluate the incidence of CRS and ICANS in a large group of patients with LBCL treated with anti-CD19 CAR T-cell therapy in the real world and to develop prognostic scoring systems for these side effects.
STUDY DESIGN: Clinical study.
ENDPOINTS: Incidence of CRS and ICANS, predictive parameters.
METHOD: The incidence of CRS and ICANS was assessed in 925 patients with LBCL from the French DESCAR-T registry who received axicabtagene ciloleucel
Prognostic scoring systems for severe CRS or ICANS
CRS prognostic scoring system ICANS prognostic scoring system
(axi-cel; 62%) or tisagenlecleucel (tisa-cel; 38%) after at least two prior lines of therapy. Prognostic scoring systems for severe (i.e. grade-3 or higher) CRS and ICANS were developed using a training set (60% of patients) and an internal validation set (40% of patients). Predictive parameters were identified by multivariate analysis. The scoring systems were externally validated in an independent international cohort of patients.
RESULTS: Overall, 84.1% of the 925 patients experienced CRS of any grade (8.0% had severe CRS) and 40.5% experienced ICANS of any grade (12.1% had severe ICANS). Prognostic scoring systems for severe CRS and ICANS were constructed using the main risk factors identified by multivariate analysis (Table). The incidence of severe CRS was 5.9% in patients with a score ≤2 on the CRS prognostic scoring system (low risk) versus 19.8% with a score >2 (high risk). The incidence of severe ICANS was 2.6% in the low-risk category (i.e. score ≤2) versus 18.3% in the high-risk category (i.e. score >2). Consistent results were obtained in the external validation cohort.
CONCLUSION: Two novel prognostic scoring systems were developed that can identify patients with large B-cell lymphoma who have an increased risk of severe CRS or ICANS, respectively, after anti-CD19 CAR T-cell therapy.
https://doi.org/10.1186/s13045-024-01579-w
OUTCOMES OF SUBSEQUENT ANTI-LYMPHOMA THERAPIES AFTER SECOND-LINE AXICABTAGENE CILOLEUCEL OR STANDARD OF CARE IN ZUMA-7
Blood Advances, 2024 June 11; 8(11):2982–90
AUTHORS: Ghobadi A, Munoz J, Westin JR, Locke FL, Miklos DB, Rapoport AP, Perales MA, Reagan PM, McGuirk J, Jacobson CA, Kersten MJ, Avivi I, Peng A, Schupp M, To C, Oluwole OO CENTRE FOR CORRESPONDENCE: Washington University School of Medicine, St Louis, Missouri, USA
BACKGROUND & AIM: In the phase-3 ZUMA-7 trial, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel) was associated with longer survival than the standard of care as second-line treatment for adults with early, relapsed or refractory, large B-cell lymphoma (LBCL). Following these results, CAR T-cell therapy has been proposed as the new second-line standard of care for these patients. However, the optimal management of those who do not respond to, or experience disease progression during, second-line treatment is unknown. The aim of this study was to describe outcomes in patients from the ZUMA-7 trial who received subsequent anti-lymphoma therapy.
METHOD: In the ZUMA-7 trial, adults with relapsed or refractory LBCL were randomized 1:1 to axi-cel (n=180) or the standard of care (n=179), which comprised platinum-based chemoimmunotherapy followed by high-dose chemotherapy and autologous stem-cell transplantation (SCT) in those with a partial or complete response. Third-line anti-lymphoma therapy was given at the investigator’s discretion. Survival was assessed from the start of third-line therapy.
RESULTS: Of the 179 patients in the standard-of-care arm, 127 (71%) required third-line therapy: 68 received cellular immunotherapy and 59 received other thirdline therapies. The median progressionfree survival time in these two subgroups was 6.3 and 1.9 months, respectively, and the median overall survival time was 16.3 and 9.5 months, respectively. Of the 180 patients in the axi-cel arm, 84 (47%) required third-line therapy: eight received cellular immunotherapy and 60 received chemotherapy. The median progressionfree survival time in these two subgroups was 3.5 and 1.7 months, respectively, and the median overall survival time was not reached and 8.1 months, respectively. Of the 60 patients who received chemotherapy, 10 underwent SCT following salvage chemotherapy: both median progression-free survival (11.5 versus 1.6 months) and median overall survival (17.5 versus 7.2 months) were longer than in patients who did not undergo SCT. Of the eight patients in the axi-cel arm who received third-line cellular immunotherapy, six underwent any-line SCT and were alive at data cut-off.
CONCLUSIONS: In patients with relapsed or refractory LBCL who progressed after second-line axicabtagene ciloleucel or the standard of care, third-line cellular immunotherapy was associated with longer survival than third-line chemotherapy or other therapies. When possible, stem cell transplantation prolonged survival.
https://doi.org/10.1182/bloodadvances.2023011532
COMPARATIVE EFFECTIVENESS OF 6X R-CHOP21 VERSUS 6X RCHOP21 + 2 R FOR PATIENTS WITH ADVANCED-STAGE DIFFUSE
LARGE B-CELL LYMPHOMA
Blood Cancer Journal, 2024 September 12; 14(1):157
AUTHORS: Maas CH, van Klaveren D, Durmaz M, Visser O, Issa DE, Posthuma EF, Zijlstra JM, Chamuleau ME, Lugtenburg PJ, Kersten MJ, Dinmohamed AG CENTRE FOR CORRESPONDENCE: Department of Public Health, Erasmus University Medical Centre, Rotterdam, the Netherlands
BACKGROUND & AIM: The preferred first-line treatment for advanced, diffuse large B-cell lymphoma (DLBCL) is a combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone administered in six cycles over 21 days (i.e. 6x R-CHOP21) or 6x R-CHOP21 plus two additional rituximab doses (i.e. 6x R-CHOP21 + 2 R). Currently, the choice between these two regimens is often guided by an interim positron-emission tomography (PET) scan after two cycles of R-CHOP, with 6x R-CHOP21 + 2 R recommended for patients with positive interim PET findings. However, no randomised trial has compared 6x R-CHOP21 and 6x R-CHOP21 + 2 R in these patients. The aim of this study, therefore, was to compare survival outcomes in patients with advancedstage DLBCL who received 6x R-CHOP21 or 6x R-CHOP21 + 2 R at a time when treatment was not routinely guided by interim PET findings.
STUDY DESIGN: National populationbased study.
ENDPOINTS: Event-free survival, overall survival.
METHOD: A search of the Netherlands Cancer Registry identified 1577 adults who were diagnosed with advancedstage DLBCL between 2014 and 2018: 672 (43%) completed treatment with 6x R-CHOP21, whereas 905 (57%) received
6x R-CHOP21 + 2 R. Propensity score matching was used to mitigate confounding by balancing characteristics across treatment groups.
RESULTS: In all patients, the median eventfree survival time was 4.44 years (interquartile range 3.84–5.32 years) and the median overall survival time was 4.44 years (IQR 3.84–5.29 years). At 5 years, there was no significant difference between patients treated with 6x RCHOP21 + 2 R and those receiving 6x R-CHOP21 in either event-free survival (hazard ratio 0.89, 95% confidence interval 0.72–1.09; p-value of weighted log-rank test=0.23) or overall survival (HR 0.93, 95% CI 0.73–1.18; p=0.53). However, in an exploratory analysis stratified by International Prognostic Index, patients with a high index score (i.e. 4–5) benefited more from 6x R-CHOP21 + 2 R than 6x R-CHOP21: the 5-year absolute risk difference was 16.8 percentage points (95% CI –0.4 to 34.1 percentage points) for eventfree survival and 12.1 percentage points (95% CI –5.4 to 29.6 percentage points) for overall survival.
CONCLUSIONS: Among all study patients with advanced-stage DLBCL, 5-year event-free and overall survival were comparable with 6x R-CHOP21 and 6x R-CHOP21 + 2 R at a time when interim PET guidance was not routine. However, high-risk patients tended to have better survival with 6x R-CHOP21 + 2 R.
https://doi.org/10.1038/s41408-024-01137-0
LOGISTICAL CHALLENGES OF CAR T-CELL THERAPY IN NON-HODGKIN LYMPHOMA: A SURVEY
OF HEALTHCARE PROFESSIONALS
Future Oncology, 2024 September 13; Epub ahead of print
AUTHORS: Sureda A, Adam SE, Yang S, Griffin E, Baker J, Johnston K, Navarro FR, Alhasani S, Chhibber A, Wang A, Mutebi A CENTRES: Institut Català d’Oncologia, Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, Barcelona, Spain; Broadstreet HEOR, Vancouver, Canada; Genmab US Inc, Plainsboro, New Jersey, USA; and Abbvie Inc, North Chicago, Illinois, USA
BACKGROUND & AIM: Chimeric antigen receptor (CAR) T-cell therapy is an option for patients with relapsed or refractory non-Hodgkin lymphoma (NHL). However, treatment is complex. The aim of this study was to investigate the logistical challenges faced by healthcare professionals, patients and care-givers during the CAR T-cell process.
STUDY DESIGN: Cross-sectional mixedmethods study.
ENDPOINT: Logistical challenges during CAR T-cell therapy.
METHOD: In the first phase of the study, 25 healthcare professionals in the United States and the United Kingdom with experience of CAR T-cell therapy for relapsed or refractory NHL participated in a semistructured interview designed to identify themes for a quantitative survey. In the second phase, 133 healthcare professionals completed an online quantitative survey about the logistical challenges encountered during each stage of the CAR T-cell process: (a) referral; (b) eligibility determination; (c) pre-infusion procedures (e.g. leukapheresis); (d) CAR T-cell infusion; (e) immediate post-infusion monitoring; and (f) long-term follow-up.
RESULTS: Four main themes emerged from the qualitative interviews: (a) time and administration issues; (b) access to
insurance; (c) travel and accommodation; and (d) caregiver support. More than 80% of respondents in the quantitative survey were physicians; they had referred a median of 15 patients for CAR T-cell therapy in the previous 24 months. For each stage of the CAR T-cell process, ≥60% of healthcare professionals identified at least two logistical challenges. The most common were: (a) long waiting times (e.g. for CAR T-cell manufacture or insurance or health authority approval); (b) limited hospital capacity; (c) the need for caregiver support; and (d) out-of-pocket expenses (e.g. for travel and accommodation at specialized centres and for loss of income). Out-of-pocket costs were a greater concern in the United States than in the United Kingdom, as was insurance coverage. More than half of healthcare professionals indicated that rapid disease progression while awaiting CAR T-cell infusion was a reason for not proceeding. Healthcare professionals estimated that the mean time between leukapheresis and infusion was 21 days, that patients spent a mean of 5 days before infusion and 12 days during and after infusion in nearby accommodation and that 67% of patients had support from an informal or unpaid caregiver during treatment.
CONCLUSIONS: Numerous logistical challenges associated with CAR T-cell therapy for relapsed or refractory NHL were identified. Streamlined processes and more convenient, alternative treatments are needed.
https://doi.org/10.1080/14796694.2024.2393566
OPTIMIZING THE POST-CAR T MONITORING PERIOD FOR AXICABTAGENE
MARALEUCEL
Blood Advances, 2024 October 22; 8(20):5346–54
AUTHORS: Ahmed N, Wesson W, Lutfi F, Porter DL, Bachanova V, Nastoupil LJ, Perales MA, Maziarz RT, Brower J, Shah GL, Chen AI, Oluwole OO, Schuster SJ, Bishop MR, McGuirk JP, Riedell PA
CENTRE FOR CORRESPONDENCE: Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA
BACKGROUND & AIMS: As CD19directed chimeric antigen receptor (CAR) T-cell therapies can lead to the life-threatening toxicities of cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS), patients in the United States are required to stay within 2 hours’ travel of their treatment centre for 4 weeks after CAR T-cell therapy for monitoring. This requirement is costly, burdensome and can be a barrier to patients and their families. The aims of this study were to investigate the onset and duration of CRS and ICANS in patients receiving CAR T-cell therapy and to identify causes of non-relapse death.
STUDY DESIGN: Retrospective observational study.
ENDPOINTS: Incidence and timing of CRS and ICANS, causes of non-relapse death.
Incidence of any-grade CRS and ICANS after CAR T-cell therapy
METHOD: The study involved data from the Cell Therapy Consortium registry on 475 patients with relapsed or refractory, large B-cell lymphoma (LBCL) who underwent CAR T-cell therapy at nine United States’ centres between 2018 and 2023: 216 (45%) received axicabtagene ciloleucel (axi-cel), 158 (33%) received tisagenlecleucel (tisa-cel) and 101 (21%) received lisocabtagene maraleucel (liso-cel). The American Society of Transplantation and Cellular Therapeutics (ASTCT) consensus grading system was used to assess both CRS and ICANS. Cytopenia and infections were graded using National Cancer Institute Common Terminology Criteria (CTCAE) version 5.
RESULTS: The incidence of new-onset CRS and ICANS in the 14 days after CAR T-cell infusion is shown in the Table for axi-cel, tisa-cel and liso-cel. After 14 days, there was one case of ICANS (with tisa-cel) but no new cases of CRS. The main cause of non-relapse death in the early follow-up period was ICANS: the mortality rate associated with ICANS was 1.1% by day 28. After 28 days, most deaths were due to infection.
CONCLUSIONS: In patients who received CAR T-cell therapy for LBCL, new-onset CRS or ICANS seldom occurred more than 14 days after infusion. Most cases of nonrelapse death beyond day 28 were due to infection.
https://doi.org/10.1182/bloodadvances.2023012549
SAFETY AND EFFICACY OF ODRONEXTAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
Annals of Oncology, 2024 November; 35(11):1039–47
AUTHORS: Kim TM, Taszner M, Novelli S, Cho SG, Villasboas JC, Merli M, Jiménez-Ubieto A, Tessoulin B, Poon LM, Tucker D, Walewski J, Yi S, Song Y, Chong G, Bachy E, Guidez S, Alonso A, Jagadeesh D, Zhang W, Magnano L, Iskierka-JaŻdŻewska E, Tani M, Shen B, Uppala A, Zhu M, Shariff S, Brouwer-Visser J, Chaudhry A, Mohamed H, Ambati S, Luminari S, for the ELM-2 investigators
CENTRE FOR CORRESPONDENCE: Seoul National University Cancer Research Institute, Seoul, South Korea
BACKGROUND & AIM: Patients with follicular lymphoma who receive anti-CD20 monoclonal antibodies invariably relapse and outcomes worsen with each successive relapse. Consequently, new treatments are needed for patients with relapsed or refractory follicular lymphoma. Odronextamab is a human CD20 × CD3 bispecific antibody that engages cytotoxic T cells and malignant B cells, resulting in malignant cell death. In the ELM-1 phase-I study of heavily pretreated patients with B-cell non-Hodgkin lymphoma, odronextamab was associated with a high response rate in those with grade 1–3a follicular lymphoma. The aim of this paper was to report the primary analysis of the effects of odronextamab in patients with relapsed or refractory follicular lymphoma who took part in the ELM-2 phase-2 study.
STUDY DESIGN: Open-label phase-2 study.
ENDPOINTS: Objective response rate (primary endpoint), progression-free and overall survival time, adverse events.
METHOD: The study involved 128 patients (median age 61 years) who had relapsed or refractory follicular lymphoma after at least two lines of systemic therapy; 109 (85%) had advanced-stage disease (i.e. Ann Arbor stage III–IV) and 74% were refractory to anti-CD20 antibody treatment. All patients received odronextamab intravenously for four 21-day cycles, with step-up dosing
in cycle 1 to reduce the risk of cytokine release syndrome. Subsequently, odronextamab was administered at a maintenance dose of 160 mg every 2 weeks until disease progression or unacceptable toxicity. In patients who had a complete response lasting ≥9 months, dosing was reduced to 160 mg every 4 weeks. Treatment responses were assessed by independent central review using the Lugano criteria. The median follow-up time was 20.1 months.
RESULTS: Overall, 95% of patients completed cycle 1 and 85% completed ≥4 cycles. The objective response rate was 80.0% and the complete response rate was 73.4%. The median duration of a complete response was 25.1 months, the median progression-free survival time was 20.7 months and the median overall survival time was not reached. Treatment-emergent adverse events occurred in all patients: the most common any-grade events were cytokine release syndrome (56% of patients), neutropenia (39%) and pyrexia (38%) and the most common grade-3 or -4 events were neutropenia (32%), anaemia (12%) and a low neutrophil count (12%). Treatmentemergent adverse events led to treatment discontinuation in 16% of patients.
CONCLUSIONS: In patients with heavily pretreated, relapsed or refractory follicular lymphoma, odronextamab was associated with a complete response rate of 73.4%. Adverse events were generally manageable.
https://doi.org/10.1016/j.annonc.2024.08.2239
RISK OF SECOND TUMORS AND T-CELL LYMPHOMA AFTER CAR T-CELL THERAPY
The New England Journal of Medicine, 2024 June 13; 390(22):2047–60
AUTHORS: Hamilton MP, Sugio T, Noordenbos T, Shi S, Bulterys PL, Liu CL, Kang X, Olsen MN, Good Z, Dahiya S, Frank MJ, Sahaf B, Mackall CL, Gratzinger D, Diehn M, Alizadeh AA, Miklos DB
CENTRE FOR CORRESPONDENCE: Division of Oncology, Department of Medicine, Stanford University, Stanford, California, USA
BACKGROUND & AIMS: Secondary neoplasms have been reported to occur after chimeric antigen receptor (CAR) T-cell therapy. Of particular concern are secondary T-cell lymphomas, which may be associated with integration of the CAR T-cell viral vector into malignant lymphocytes. The aims of this study were to determine the incidence of secondary tumours in patients who receive adoptive cellular therapies and to characterize the molecular profile of a single case of a lethal T-cell lymphoma diagnosed after CAR T-cell therapy for diffuse large B-cell lymphoma (DLBCL).
STUDY DESIGN: Retrospective clinical study and case analysis.
ENDPOINTS: Secondary tumours, molecular characteristics of a secondary T-cell lymphoma.
METHOD: The occurrence of secondary tumours was investigated in 724 patients who received a total of 791 therapeutic cell infusions (96.6% with CAR T cells) at Stanford University Medical Center between 2016 and 2024. The development of a lethal secondary T-cell lymphoma 54 days after axicabtagene ciloleucel therapy for stage-IV DLBCL in one patient was investigated using a broad array of molecular, genetic, and cellular techniques, which assessed both lymphomas, CAR T cells and normal haematopoietic cells.
RESULTS: Overall, 25 second tumours were identified in the 724 patients during a median follow-up of 15 months: 14 were haematological tumours and 11 were solid tumours. The 3-year cumulative incidence of haematological second tumours was only 6.5%. In the patient who developed a lethal secondary T-cell lymphoma, the T-cell lymphoma was characterized by a CD3+CD4+CD8 immunophenotype, whereas the original DLBCL expressed CD19 and CD20. Molecular profiling revealed that the DLBCL harboured a chromosome 3q amplification and chromosome 7 deletion, whereas the T-cell lymphoma had distinct genetic features, including a chromosome 1q amplification and chromosome 6q deletion. Both tumours tested positive for Epstein-Barr virus and shared mutations in TET2 and DNMT3A, suggesting a common progenitor cell. There was no evidence of integration of the CAR T-cell viral vector. The development of the T-cell lymphoma appeared to be driven by other mechanisms, including Epstein-Barr virus activation.
CONCLUSIONS: The 3-year cumulative incidence of haematological second tumours in a large group of patients who received CAR T-cell therapy was 6.5%. There was only one secondary T-cell lymphoma among 724 patients; molecular analysis found no evidence that the engineered retroviral vector contributed to its development.
https://doi.org/10.1056/NEJMoa2401361
ECONOMIC EVALUATION OF ANTI-CD19 CAR T-CELL PATHWAY FOR LARGE B-CELL LYMPHOMAS IN THE REAL-LIFE SETTING:
THE EXPERIENCE OF AN ITALIAN HUB CENTER IN THE FIRST THREE YEARS OF ACTIVITY
Annals of Hematology, 2024 July; 103(7):2499–509
AUTHORS: Di Staso R, Casadei B, Gentilini M, Guadagnuolo S, Pellegrini C, Broccoli A, Gori D, Masetti R, Stefoni V, Bonifazi F, Zinzani PL, Argnani L
CENTRES: Dipartimento Di Scienze Mediche E Chirurgiche and Dipartimento Di Scienze Biomediche E Neuromotorie, Università Di Bologna, Bologna; and Istituto Di Ematologia Seràgnoli and Pediatric Oncology and Hematology, IRCCS Azienda Ospedaliero–Universitaria Di Bologna, Bologna, Italy
BACKGROUND & AIM: Chimeric antigen receptor (CAR) T-cell therapy is one of the most expensive cancer treatments. However, few publications have reported the full cost of treatment – most have reported costs only for infused patients, rather than for all patients who undergo leukapheresis with the intention of receiving CAR T-cell therapy. The aim of this study was to assess the cost of CAR T-cell therapies in patients with relapsed or refractory, large B cell lymphoma (LBCL) who were treated in a real-world setting.
STUDY DESIGN: Retrospective data analysis.
ENDPOINT: Treatment costs.
METHOD: The study included data on all 80 patients (median age 57.5 years) with aggressive, relapsed or refractory LBCL who underwent leukapheresis for CAR T-cell therapy at a single Italian centre between 2019 and 2022. Total costs and medical resource consumption for CAR T-cell therapy were calculated on an intention-to-treat basis. Costs were assessed from leukapheresis until the last available follow up or until the patient (whether infused with CAR T cells or not) left the CAR T-cell treatment pathway due to a decision to not infuse, death, progression or further antilymphoma therapy. The costs of personnel time, examinations, hospitalization, procedures and medications were included. The
median follow-up time in the intention-totreat population was 16 months.
RESULTS: Of the 80 patients, 59 received CAR T-cell infusions. Apart from the cost of the CAR T-cell products, the main costs in the CAR T-cell treatment pathway were for hospitalization (43.9% of additional costs), followed by the cost of patient examinations and procedures (26.3%) and the cost of other drugs needed (e.g. for bridging therapy and adverse event management; 25.4%). Overall, 63% of non-CAR T-cell medication costs were for the treatment of adverse events (both infections and other complications) that occurred within 30 days of CAR T-cell infusion. For the intentionto-treat population of 80 patients, the total pathway costs of time, examinations, transfusions, hospitalizations, apheresis and medications (excluding CAR T-cell products) that led to 59 patients receiving CAR T-cell infusions was €4,360,384, which corresponds to a cost of around €74,000 per infused patient.
CONCLUSIONS: For patients with relapsed or refractory LBCL, CAR T-cell therapy was associated with a cost (in addition to CAR T-cell products) of €74,000 for each patient who received an infusion. After exclusion of the cost of CAR T-cell products, the largest cost was for hospitalization and the main non-CAR T-cell medication costs were for treating adverse events.
https://doi.org/10.1007/s00277-024-05766-0
framıngham
Verkorte Productinformatie Yescarta®▼ ▼Dit geneesmiddel is onderworpen aan aanvullende monitoring.
on non-Hodgkin lymphoma
SAMENSTELLING: Elke patiëntspecifieke infuuszak met Yescarta bevat axicabtagen-ciloleucel in een batchafhankelijke concentratie van autologe T-cellen die genetisch zijn gemodificeerd om een anti-CD19, chimere antigeenreceptor tot expressie te brengen (CAR-positieve levensvatbare T-cellen). Het geneesmiddel is verpakt in één infuuszak met in totaal een celdispersie voor infusie voor een doeldosis van 2 × 106 anti- CD19 CARpositieve levensvatbare T-cellen per kg lichaamsgewicht, met een maximum van 2 × 108 anti- CD19 CAR-positieve levensvatbare T-cellen, gesuspendeerd in een cryopreservatieve oplossing. INDICATIES: *Behandeling van volwassen patiënten met diffuus grootcellig B cellymfoom (DLBCL) en hooggradig B cellymfoom (HGBL) dat recidiveert binnen 12 maanden na voltooiing van, of dat refractair is voor eerstelijns chemoimmunotherapie; *Behandeling van volwassen patiënten met recidiverend of refractair diffuus grootcellig B-cellymfoom (DLBCL) en primair mediastinaal grootcellig B-cellymfoom (PMBCL), na twee of meer lijnen systemische therapie; *behandeling van volwassen patiënten met recidiverend of refractair folliculair lymfoom (FL) na drie of meer lijnen systemische therapie.. CONTRA-INDICATIES: Overgevoeligheid voor de werkzame stof of voor een van de hulpstoffen of voor gentamicine (een mogelijk residu). Overweeg de contra-indicaties voor lymfodepletie-chemotherapie. BIJZONDERE WAARSCHUWINGEN EN VOORZORGEN BIJ GEBRUIK: Algemeen: Uitsluitend bedoeld voor autoloog gebruik en mag in geen geval aan andere patiënten worden toegediend. Vóór de infusie moet worden gecontroleerd of de identiteit van de patiënt overeenkomt met de patiëntgegevens op de Yescarta-infuuszak en cassette. Yescarta mag niet worden toegediend als de informatie op de productetiketten niet overeenkomt met de identiteit van de patiënt. Waarschuwingen en voorzorgen bij lymfodepletie-chemotherapie moeten in overweging worden genomen. Redenen voor uitstel behandeling: Vanwege de risico’s die in verband worden gebracht met een behandeling met Yescarta, moet de infusie worden uitgesteld als de patiënt last krijgt van één van de volgende aandoeningen: *Onopgeloste ernstige bijwerkingen (met name pulmonaire bijwerkingen, cardiale bijwerkingen of hypotensie) met inbegrip van bijwerkingen van eerdere chemotherapieën; *Actieve, niet onder controle gebrachte infectie; *Actieve graft-versus-hostziekte (GVHD). In sommige gevallen kan de behandeling worden uitgesteld na toediening van een regime van lymfodepletie- chemotherapie. Als de infusie wordt uitgesteld tot later dan 2 weken nadat de patiënt lymfodepletie- chemotherapie heeft gehad, moet er opnieuw een regime met lymfodepletie- chemotherapie worden toegediend. Controle na infusie: patiënten moeten de eerste 7 dagen na infusie dagelijks gecontroleerd worden op tekenen en symptomen van mogelijk CRS, neurologische voorvallen en andere toxiciteiten. Artsen kunnen gedurende de eerste 7 dagen of bij de eerste tekenen of symptomen van CRS en/of neurologische voorvallen een ziekenhuisopname in overweging nemen. Als de eerste 7 dagen na infusie zijn verstreken, moet de patiënt worden gecontroleerd op basis van het inzicht van de arts Overdracht van een infectieus agens: Hoewel Yescarta op steriliteit en mycoplasma wordt getest bestaat er een risico op overdracht van infectieuze agentia. Beroepsbeoefenaren in de gezondheidszorg die Yescarta toedienen moeten patiënten na de behandeling daarom controleren op tekenen en symptomen van infectie en, zo nodig, op passende wijze behandelen. Serologische testen: Voer screening op HBV, HCV en hiv uit voordat er cellen worden afgenomen voor de vervaardiging van Yescarta. Bloed-, orgaan-, weefsel- en celdonatie: Doneer geen bloed, organen, weefsels en cellen voor transplantatie. Primair CZS-lymfoom: Er is geen ervaring van Yescarta bij patienten met primair CZS-lymfoom. Daarom zijn de voordelen/risico’s bij deze populatie niet vastgesteld. Cytokine-release-syndroom: Vrijwel alle patiënten hebben een zekere mate van CRS ervaren. Ernstige CRS, met inbegrip van levensbedreigende en fatale reacties, werd zeer vaak waargenomen met een tijd tot eerste symptomen van 1 tot 12 dagen in ZUMA-1 en ZUMA-7, en 1 tot 11 dagen in ZUMA-5. Zie SmPC. Neurologische bijwerkingen: Ernstige neurologische bijwerkingen, ook wel immuun-effectorcel-geassocieerd neurotoxiciteitssyndroom (ICANS, immune effector cell-associated neurotoxicity syndrome) genoemd, zijn zeer vaak waargenomen bij patiënten, en konden levensbedreigend of fataal zijn. Patiënten met een voorgeschiedenis van stoornissen van het centraal zenuwstelsel, zoals insulten of cerebrovasculaire ischemie, kunnen een verhoogd risico lopen. Zie SmPC. Infecties en febriele neutropenie: Bij patiënten met immunosuppressie zijn levensbedreigende en fatale opportunistische infecties gemeld, waaronder uitgezaaide schimmelinfecties. Controleer patiënten op tekenen en symptomen van infectie voorafgaand aan, tijdens en na infusie en dienovereenkomstig behandelen. Dien profylactische antimicrobiële middelen conform de standaardrichtlijnen van de instelling toe. Febriele neutropenie is waargenomen bij patiënten na infusie en deze aandoening kan gelijktijdig met CRS optreden. Stel bij febriele neutropenie vast of er sprake is van infectie en er moet overwogen worden die te behandelen met breedspectrumantibiotica, vocht en andere ondersteunende zorg zoals medisch geïndiceerd. Virale reactivering: Reactivering van HBV, die in sommige gevallen leidt tot fulminante hepatitis, leverfalen en overlijden, kan optreden bij patiënten die worden behandeld met geneesmiddelen die zijn gericht tegen B cellen. Bij immuungecompromitteerde patiënten met nieuw optredende of verergerende neurologische symptomen moet rekening worden gehouden met de mogelijkheid van progressieve multifocale leuko-encefalopathie en moeten passende diagnostische beoordelingen worden uitgevoerd. Andere levensbedreigende en fatale gevallen van virale reactivering met HHV-6 zijn gemeld. Langdurige cytopenieën: Van graad 3 of hoger traden zeer vaak op na infusie, waaronder trombocytopenie, neutropenie en anemie. Patiëntbloedceltellingen moeten na infusie met Yescarta worden gecontroleerd. Hypogammaglobulinemie: Is zeer vaak waargenomen bij patiënten. Controleer de immunoglobulineconcentraties na behandeling met Yescarta en behandel met voorzorgsmaatregelen tegen infecties, antibioticaprofylaxe en immunoglobulinesubstitutie, in geval van terugkerende infecties en volgens de standaard richtlijnen. Overgevoeligheidsreacties: Er kunnen allergische reacties optreden met de infusie van Yescarta. Ernstige allergische reacties kunnen optreden met inbegrip van anafylaxie, als gevolg van DMSO of resterend gentamicine in Yescarta. Secundaire maligniteiten waaronder die met oorsprong in de T-cellen: Secundaire maligniteiten kunnen zich ontwikkelen. Er is melding gemaakt van T-celmaligniteiten na behandeling van hematologische maligniteiten met een BCMA- of CD19gerichte CAR T-celtherapie, waaronder Yescarta. Ook zijn er meldingen over T-celmaligniteiten, met inbegrip van CAR-positieve maligniteiten, binnen een paar weken tot enkele jaren na de toepassing van een CD19- of BCMA-gerichte CAR T-celtherapie. Er zijn fatale uitkomsten geweest. Patiënten moeten levenslang op secundaire maligniteiten worden gecontroleerd. Wanneer zich een secundaire maligniteit van T-cel-origine voordoet, moet er contact worden opgenomen met het bedrijf voor instructies over het afnemen van patiëntenmonsters voor testen. Tumorlysissyndroom (TLS): Controleer tekenen en symptomen van TLS en behandel voorvallen overeenkomstig de standaardrichtlijnen. CD19 - negatieve ziekte: Er is beperkte ervaring met Yescarta bij patiënten die zijn blootgesteld aan eerdere tegen CD19 gerichte therapie. Yescarta wordt niet aanbevolen bij patiënten met gerecidiveerde CD19negatieve ziekte na eerdere anti-CD19-therapie. Er wordt verwacht dat patiënten worden ingeschreven in een register om een beter begrip van de veiligheid en werkzaamheid van Yescarta op de lange termijn te krijgen. Hulpstoffen: Dit geneesmiddel bevat 300 mg natrium per infuuszak, overeenkomend met 15% van de door de WHO aanbevolen maximale dagelijkse inname van 2 g natrium voor een volwassene. BIJWERKINGEN: Zeer vaak: Infecties met niet-gespecificeerde pathogenen, virusinfecties, bacteriële infecties, febriele neutropenie, neutropenie, lymfopenie, leukopenie, anemie, trombocytopenie, Cytokine-release-syndroom, immunoglobulines verlaagd, hyponatriëmie, hypofosfatemie, hyperurikemie, hyperglykemie, verminderde eetlust, delier, slapeloosheid, encefalopathie, tremor, hoofdpijn, duizeligheid, tachycardie, aritmie, hypotensie, hypertensie, hoesten, braken, diarree, constipatie, buikpijn, misselijkheid, transaminasen verhoogd, huiduitslag, functiestoornis motoriek, skeletspierstelselpijn, koorts, oedeem, vermoeidheid, rillingen. Vaak: Schimmelinfecties, coagulopathie, overgevoeligheid, hypokaliëmie, hypocalciëmie, hypoalbuminemie, uitdroging, gewicht verlaagd, angst, affectieve stoornis, ataxie, insulten waaronder status epilepticus, hemiparese, gelaatsparalyse, neuropathie perifeer, myoclonus, gezichtsvermogen afgenomen, hartstilstand, hartfalen, trombose, respiratoir falen, hypoxie, pleurale effusie, pulmonaal oedeem, dyspneu, neusontsteking, dysfagie, droge mond, hyperbilirubinemie, nierfunctie verminderd, infusie gerelateerde reacties, pijn. Soms: Hematofagocytaire lymfohistiocytose, quadriplegie, ruggenmergoedeem, myelitis, dyscalculie, rabdomyolyse, multiorgaandisfunctiesyndroom. Zelden: Secundaire maligniteit met oorsprong in de T-cellen. Zie SmPC. FARMACOTHERAPEUTISCHE GROEP: Andere antineoplastische middelen, antineoplastische cel- en gentherapie, ATC- code: L01XX70. AFLEVERSTATUS: U.R. PRIJS: Zie Z-index. VERGOEDING: Op verstrekking van dit geneesmiddel bestaat aanspraak voor de indicatie DLBCL en PMBCL, na twee of meer lijnen systemische therapie krachtens en onder de voorwaarden van de Nederlandse Zorgverzekeringswet en begeleidende uitvoeringswetgeving. VERGUNNING: EU/1/18/1299/001 REGISTRATIEHOUDER: Kite Pharma EU B.V., Hoofddorp LOKALE VERTEGENWOORDIGER: Gilead Sciences Netherlands B.V., Claude Debussylaan 22, 1082 MD Amsterdam DATUM: Deze tekst is het laatst herzien in september 2024. NL-CTH-2020-01-0023 v16.0. Voor de volledige productinformatie zie de geregistreerde Samenvatting van de Productkenmerken.
Eventvrije overleving2
Risicopatiënten
Maanden
ZUMA-7-studie:# YESCARTA® laat significant verschil zien in eventvrije overleving (EFS) versus tweedelijns standaardbehandeling* bij grootcellig B-cellymfoom R/R ≤ 12 maanden1
Standaardbehandeling
Yescarta heeft tevens een significante verbetering in overleving (OS) aangetoond: 55% van de patiënten in leven na 4 jaar.^2
Yescarta is, onder andere, geïndiceerd voor de behandeling van volwassen patiënten met diffuus grootcellig B-cellymfoom (DLBCL) en hooggradig B-cellymfoom (HGBL) dat recidiveert binnen 12 maanden na voltooiing van, of dat refractair is voor eerstelijns chemo-immunotherapie. 3
# De werkzaamheid en veiligheid van Yescarta bij volwassen patiënten met R/R grootcellig B-cellymfoom (LBCL) werden aangetoond in een gerandomiseerd, open-label multicentrisch fase 3-onderzoek: ZUMA-7 (N=359). 3
* Gedefinieerd als 2 tot 3 cycli standaard chemo-immunotherapie gevolgd door hooggedoseerde therapie en autologe stamceltransplantatie bij degenen met ziekterespons. 3
^ De geschatte totale overleving na 4 jaar was 54,6% (95% BI: 47,0 - 61,6) met Yescarta en 46,0% (95% BI, 38,4 - 53.2) met standaardbehandeling. 2
▼ Dit geneesmiddel is onderworpen aan aanvullende monitoring.
Verkorte productinformatie zie elders in deze uitgave.
Referenties: 1. Locke FL, Miklos DB, Jacobsen CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B- Cell Lymphoma. N Engl J Med 2022; 386:640-654. 2. Westin JR, Oluwole OO, Kersten MJ, et al. Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma. N Engl J Med 2023;389:148-57. 3. Yescarta SmPC, huidige versie.
