Abecma (idecabtagene vicleucel) / BMS, 2seventy bio - LARVOL DELTA

G-BA, IQWiG Find "No Proven" Added Benefit for Abecma (NAVLIN DAILY) - "The Joint Federal Health Committee (G-BA) has determined that Abecma (idecabtagene vicleucel) does not offer any proven additional benefit over patient-individualized standard therapies for adult R/R multiple myeloma patients who have undergone at least two prior therapies, including an immunomodulator, a proteasome inhibitor, and an anti-CD38 antibody, and who have shown disease progression. Abecma costs approximately EUR 400,000 per patient, not including hospitalization and post-treatment monitoring costs. Given the therapy's high cost and the lack of confirmed clinical advantages, G-BA has decided on an ultimate additional benefit rating of 'not proven'....The G-BA's assessment relied heavily on data from the KarMMa-3 clinical trial..."

Reimbursement • Multiple Myeloma

Safety assessment of anti-B cell maturation antigen chimeric antigen receptor T cell therapy: a real-world study based on the FDA adverse event reporting system database. (PubMed, Front Immunol) - "However, comprehensive real-world safety studies have been lacking for the newly marketed CAR-T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which target B cell maturation antigen, especially regarding the risk of secondary malignancies. This study provides a foundation for understanding the safety profile of CAR-T cell therapy, particularly in relation to the emergence of secondary malignancies. Such insights are helpful for clinical decision-making and the safe and effective utilization of these therapeutic agents."

Adverse events • CAR T-Cell Therapy • Journal • Real-world • Real-world evidence • Aplastic Anemia • Hematological Malignancies • Multiple Myeloma • Oncology

Idecabtagene-vicleucel in the treatment of multiple myeloma (SIE 2024) - "Sponsored by BRISTOL MYERS SQUIBB"

Hematological Malignancies • Multiple Myeloma • Oncology

Cytotoxic CD4+ T cells are major drivers of side effects and response after chimeric antigen receptor T cells against BCMA (IMW 2024) - "Cytotoxic CD4+ T cells play a significant role in the response and side effects following BCMA-directed CAR T cell therapy. This effect is more pronounced in Cilta-cel compared to Ide-cel."

Adverse events • CAR T-Cell Therapy • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • CD4 • CD8

A Comparison of Standard of Care Idecabtagene Vicleucel and Ciltacabtagene Autoleucel CAR T-cell Therapy in Relapsed or Refractory Multiple Myeloma (IMW 2024) - "Our results suggest a less favorable safety profile but higher efficacy and better survival for cilta-cel compared to ide-cel in the SOC setting. *DH, LP, DD, YL, KP, & SS contributed equally."

CAR T-Cell Therapy • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Real-world comparison of overall survival between BCMA - bispecific and CAR-T therapies in multiple myeloma (ESMO 2024) - "For relapsed/refractory MM, teclistamab and two CAR-T therapies, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), are approved by the FDA after four or more lines of therapy. This is the first report comparing survival in a real-world setting between BCMA CAR-Ts and bispecifics. We found that CAR-T improved survival over patients receiving only bispecifics. Older patients and those who did not receive transplants particularly had better OS with CAR-T."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology

CAR-T cell therapy in relapsed or refractory multiple myeloma and access in Turkey. (PubMed, Front Med (Lausanne)) - "Two anti-BCMA CAR-T products are available for treating relapsed or refractory MM: idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). However, there are key similarities and differences regarding these agents, unknowns regarding their comparative efficacy and toxicity, and mechanisms underlying resistance to these new immunotherapies. This review discusses CAR-T cell therapy in relapsed refractory MM, with a focus on efficacy, toxicities, and the evolving trajectories of these therapies in the USA, as well as access in Turkey."

CAR T-Cell Therapy • Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

The risk of secondary cancers from CAR-T therapies is similar to that of other standard therapies [Google translation] (ConSalud.es) - "Recently, alarm bells have been ringing that CAR-T therapies can cause second primary malignancies (SPM). However, a new systematic review and meta-analysis suggests that the frequency of SPM that arose in cancer survivors after treatment with CAR-T cell therapy was statistically comparable to the frequency of SPM after other standard-of-care therapies...Rejeski and team conducted a systematic review and meta-analysis of clinical trials in which adult patients with lymphoma or multiple myeloma received one of six currently approved CAR T-cell therapies: idecabtagene vicleucel...lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel...tisagenlecleucel...brexucabtagene autoleucel...or axicabtagene ciloleucel...After a median follow-up of 21.7 months, 5.8% of patients developed a PMS....Of the 326 SPMs identified in this analysis, hematologic malignancies, including myelodysplastic syndrome and acute myeloid leukemia , accounted for the largest proportion of SPMs, at 37%."

Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Updates on CAR T cell therapy in multiple myeloma. (PubMed, Biomark Res) - "Ide-cel and cilta-cel stand as the only two FDA-approved BCMA-targeted CAR T-cells for MM patients, a recognition achieved despite extensive preclinical and clinical research efforts in this domain. Consequently, ongoing CAR T-cell trials are diligently addressing these challenges and barriers. In this review, we provide an overview of the effectiveness of currently available CAR T-cell treatments for MM, explore the primary resistance mechanisms to these treatments, suggest strategies for improving long-lasting remissions, and investigate the potential for combination therapies involving CAR T-cells."

CAR T-Cell Therapy • Journal • Review • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

CAR-T therapy pulmonary adverse event profile: a pharmacovigilance study based on FAERS database (2017-2023). (PubMed, Front Pharmacol) - "Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs...This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers."

Adverse events • Journal • Oncology • Respiratory Diseases

Evaluation of Anti-CAR Linker mAbs for CAR T Monitoring after BiTEs/bsAbs and CAR T-Cell Pretreatment. (PubMed, Biomedicines) - "We found a highly specific and sensitive CAR detection using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel...Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel, or Ide-cel, respectively. Cilta-cel (containing a monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but are not universally applicable."

CAR T-Cell Therapy • Journal

Comparing the Differences in Adverse Events among Chimeric Antigen Receptor T-Cell Therapies: A Real-World Pharmacovigilance Study. (PubMed, Pharmaceuticals (Basel)) - "The BCMA-targeting drugs idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) were found to be associated with parkinsonism, which were not observed in CD19-targeting drugs. Tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel) exhibited cerebrovascular accident-related AEs, graft versus host disease, and abnormal coagulation indices...The number of positive signals for cardiopulmonary toxicity associated with drugs targeting CD-19 is greater. Clinicians should assess patients prior to medication and closely monitor their vital signs, mental status, and laboratory parameters during treatment."

Adverse events • CAR T-Cell Therapy • Journal • Real-world • Real-world evidence • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Graft versus Host Disease • Hematological Disorders • Hypotension • Immunology • Movement Disorders • Nephrology • Parkinson's Disease

Teclistamab Success in CAR-T Refractory Multiple Myeloma: A Case Presentation (SOHO 2024) - "Induction: 3 cycles of bortezomib/cyclophosphamide/ dexamethasone (VCD) and 22 radiotherapy sessions for cervical vertebral lesions...She went on to 3 cycles of carfilzomib/lenalidomide/dexamethasone (KRd). She underwent chemomobilization with cyclophosphamide 2500 mg/m2 d1 and etoposide (600 mg/m2 total) d1-3...Salvage therapy isatuximab/carfilzomib/melphalan/dexamethasone (Isa-KRd)...Interventions: Fludarabine/cyclophosphamide for lymphodepletion and ide-cel infused. She developed cytokine-release-syndrome (CRS), for which she received tocilizumab and 3 days of dexamethasone in ICU...She received subcutaneous denosumab 120 mg for bone disease... Prospective trials are needed to determine the optimal timing and use of teclistamab and other T-cell-redirecting therapies to increase the likelihood of cure for patients with myeloma."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • CD34

The Role of Maintenance Therapy in the Treatment of Newly Diagnosed Multiple Myeloma (SOHO 2024) - P1, P1/2, P2, P3 | "Introduction The concept of maintenance therapy to prolong progression-free survival (PFS) and overall survival (OS) after initial treatment for newly diagnosed multiple myeloma (NDMM) is not new-In 1975, Alexanian published results from a small study of extended melphalan and prednisone, carmustine and prednisone, or no maintenance therapy after an initial melphalan and prednisone induction therapy, actually finding a negative impact on PFS and OS with such an intervention.1 Similarly, a study of interferon administered thrice weekly after MP induction found a small but statistically insignificant PFS benefit (43 vs 35 months); however excessive toxicity forced dose reductions of IFN in 58% and discontinuation in 14%.2 Such trials underscore that a successful maintenance intervention requires an active drug or drug combination but also a reasonable side effect profile...The HOVON 65 trial was a randomized phase III trial that examined older induction..."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • CRBN • IKZF1

Bispecific T-Cell Engagers: Sequencing, BCMA, GPRC5D, and Resistance (SOHO 2024) - "Currently, both FDA-approved CAR T-cell therapies, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), target the B-cell maturation antigen (BCMA) receptor on the surface of MM cells, and two of the FDA-approved bispecific antibodies, teclistamab and elranatamab, also target BCMA...Early clinical results indicate relatively encouraging response rates from teclistamab and elranatamb post-CAR T-cell therapy,6,7 and one retrospective study suggests a relatively prolonged benefit from bispecific antibodies in general.8 However, another retrospective study indicates that PFS may be limited.9 Although antigen escape may not be central when other targets are chosen, as with talquetamab, other mechanisms, including immune exhaustion that may also occur with bispecific antibodies, anti-CAR antibodies, and alterations in the tumor microenvironment, can have a detrimental impact on later lines of therapy...Ultimately, to comprehensively answer the sequencing..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome in Relapsed and Refractory Multiple Myeloma Using the FAERS Database (SOHO 2024) - "The data were accessed on March 1, 2024, to analyze the incidence of IEC-HS associated with BCMA-targeting TCE, teclistamab, elranatamab, GPRC5D-targeting talquetamab, and 2 CAR T-cell products (idecabtagene vicleucel [ide-cel] and ciltacabtagene autoleucel [cilta-cel]). The incidence of IEC-HS is lower in MM TCE than CAR-T. While there were no reported cases of IEC-HS with newer therapies (talquetamab and elranatamab), longer follow-up is needed. CAR-T and TCE can result in fatal adverse events, including IEC-HS, with increased mortality secondary to infections."

Hematological Malignancies • Multiple Myeloma • Oncology

Efficacy and Safety of Idecabtagene Vicleucel (ide-cel) With Lenalidomide (R) Maintenance Versus R Maintenance Alone in Adult Patients With Newly Diagnosed Multiple Myeloma (NDMM) Who Have Suboptimal Response to Autologous Stem Cell Transplantation (ASCT): Phase 3 KarMMa-9 Trial (SOHO 2024) - P3 | "Other secondary endpoints are sustained MRD-negative CR for 12 months, MRD-negative CR rate, event-free survival, DOR, CR rate, time to progression, PFS2, safety, pharmacokinetics, and HRQoL. Acknowledgment: This trial is supported by 2seventybio and Celgene, a Bristol Myers Squibb Company."

Clinical • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

CART Should be Reserved for Late Relapse > 3 Lines (SOHO 2024) - "Earlier this year, the CARTITUDE-4 phase III trial results led to the approval of Cilta-Cel BCMA-directed CART for lenalidomide-refractory patients with 1 or more prior lines of therapy. The KarMMA-3 phase III trial also led to approval of Ide-Cel BCMA-directed CART for patients with 2 or more prior lines of therapy...The pros/cons of strategies will be presented in the context of disease biology and practical considerations including patient preferences. Discussion/Conclusions The presenter will make the case that CART should be reserved for late relapses given the efficacy and safety profile."

Hematological Malignancies • Multiple Myeloma • Oncology

Idecabtagene Vicleucel (Ide-Cel) Versus Standard Regimens (SRs) in Triple-Class–Exposed (TCE) Relapsed and Refractory Multiple Myeloma (RRMM): KarMMa-3 Sub-Analysis of Black Patients (SOHO 2024) - P3 | "Patients: Patients with RRMM, 2-4 prior treatment lines (including an immunomodulatory agent, proteasome inhibitor, and daratumumab), and refractory to last treatment were randomized 2:1 to ide-cel or SRs (DPd, DVd, IRd, Kd, EPd). Black patients in KarMMa-3 had numerically improved efficacy outcomes with ide-cel vs SR. Efficacy and safety were consistent with the overall population. Despite small sample size, these data show ide-cel offers clinical benefit to Black patients with TCE RRMM."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Iberdomide Versus Observation Off Therapy After Idecabtagene Vicleucel CAR-T for Multiple Myeloma (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Dec 2024 ➔ Aug 2024

Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology

Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. (PubMed, Blood) - P3 | "These results demonstrate the continued favorable benefit-risk profile of ide-cel in early-line and TCE RRMM. NCT03651128."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and efficacy of B cell maturation antigen-directed CAR T-cell therapy in patients with relapsed/refractory multiple myeloma and concurrent light chain amyloidosis. (PubMed, Eur J Haematol) - "CAR T-cell therapy led to rapid and deep responses with a median time to best response of 43 days and a hematologic very good partial response or better rate of 62.5%. Overall, we found that commercial CAR T-cell therapy was feasible, and effective in patients with RRMM and concurrent AL amyloidosis."

CAR T-Cell Therapy • Journal • Amyloidosis • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Nivolumab in Multiple Myeloma Patients After Idecabtagene Vicleucel (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Wake Forest University Health Sciences | Trial completion date: Aug 2027 ➔ Nov 2027 | Initiation date: Aug 2024 ➔ Nov 2024 | Trial primary completion date: Aug 2027 ➔ Nov 2027

Trial completion date • Trial initiation date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Chimeric antigen receptor T-cells: a review on current status and future directions for relapsed/refractory multiple myeloma. (PubMed, Front Oncol) - "The approval of the B-cell maturation antigen (BCMA)-directed CAR T, idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel) has resulted in a paradigm shift in the treatment of relapsed/refractory multiple myeloma. Herein, we provide a succinct overview of the development of CAR T-cells, manufacturing process, and associated toxicities/complications. In this review, we also recapitulate the existing literature pertaining MM CAR-T as well as emerging data from some of the ongoing clinical trials designed to mitigate the shortcomings of these agents, and improve the clinical efficacy of CAR T, especially in the relapsed/refractory setting."

CAR T-Cell Therapy • Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Comparative efficacy of ciltacabtagene autoleucel versus idecabtagene vicleucel in the treatment of patients with relapsed or refractory multiple myeloma previously treated with 2-4 prior lines of therapy: a matching-adjusted indirect comparison. (PubMed, Curr Med Res Opin) - "Cilta-cel was associated with a significant 49% reduction in risk of disease progression or death versus ide-cel (hazard ratio: 0.51 [95% confidence interval: 0.31, 0.84]; p = 0.0078). For patients with triple-class exposed RRMM treated with 2-4 prior lines of treatment, cilta-cel was found to provide superior clinical benefit over ide-cel in terms of response and progression-free survival."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology