- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
CD19-Targeting CAR T-Cell Therapy in Transformed Waldenstr (SDCC - Ballroom 20AB) - Nov 3, 2023 - Abstract #ASH2023ASH_3298; P=N/A This study shows a high efficacy of anti-CD19 CAR T-cell therapy in R/R tWM with no unexpected toxicity. Longer follow-up is needed to confirm the long-term efficacy of CAR T-cells in tWM.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Chimeric Antigen Receptor (CAR (SDCC - Ballroom 20AB) - Nov 3, 2023 - Abstract #ASH2023ASH_3297; The high NRM rate of 9% at two years highlights the importance of continued follow-up in this at-risk population. The CIBMTR is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); N00014-21-1-2954 and N00014-23-1-2057 from the Office of Naval Research.
- |||||||||| Phenotypic Drug Response Profiling Identifies Asparaginase-Based Synergistic Combinations for Very High Risk Acute Lymphoblastic Leukaemia (Grand Hyatt - Grand Hall B) - Nov 3, 2023 - Abstract #ASH2023ASH_3029;
We validated combinations of ASNase with the 8 selected drugs plus 4 drugs used in induction therapy (prednisolone, dexamethasone, vincristine and daunorubicin) using a 4x4 drug matrix in 15 high-risk ALL PDX samples...Our results identify XPO1 inhibitors as a new class of drugs with promising anti-leukaemic activity in BCP-ALL. Co-culture based DRP shows promise in identifying alternative novel sensitive synergistic combinations ex-vivo with decreased toxicity for patients who have an inadequate response to standard therapy.
- |||||||||| Machine Learning-Based Time-Series Clustering Identifies Archetypal Trajectories of Hematotoxicity after CAR T-Cell Therapy (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2579;
CAR T-cell products were axi-cel, n= 101 (25%); brexu-cel, n = 24 (6%); cilta-cel, n = 21 (5%); liso-cel, n = 46 (11%); ide-cel, n = 25 (6%); tisa-cel, 12 (3%); and investigational CD19 or CD20 CAR T-cell products, n = 174 (43%). A logistic regression model using pre-LD ANC, platelet, Hb, LDH, CRP, and ferritin showed improved discrimination and sensitivity compared to CAR-HEMATOTOX in our training set, but both models had low specificity (poor ability to
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Risk Factors and Outcomes for Hematotoxicity Following Tisagenlecleucel for Pediatric B-Acute Lymphoblastic Leukemia (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2569; While there are similarities in risk factors with the CAR-HEMATOTOX score that has been validated in adults, in CAYA with B-ALL high disease burden pre-infusion and severe inflammation post-infusion were identified as the strongest risk factors for prolonged neutropenia. Identification of risk factors unique to the CAYA B-ALL population allows for tailored risk mitigation in higher risk patients and may help improve outcomes in CAYA at increased risk of prolonged severe neutropenia following tisagenlecleucel.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Blood-Brain Barrier and Neuronal Damage during Icans in Patients Treated with Anti-CD19 CAR-T Cells (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2564; Conclusion To sum up, our data confirm a correlation between severe ICANS and elevated NFL and G-FAP serum levels. Interestingly, these data also correlate with markers of endothelial activation, suggesting an active role of BBB impairment
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
18F-FDG PET/CT Imaging Biomarkers for CAR-T Cell Therapy Outcomes in Large-B-Cell Lymphoma (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2056; Our findings indicate that standard PET features (MTV and SUVmax) predict both toxicity and efficacy of CAR-T cell therapy, while also showing correlations with systemic inflammation. Additionally, we present, for the first time, the relevance of granular radiomic features in assessing the probability of treatment success.
- |||||||||| Actionable Findings from an Unbiased Drug Screen for Novel Single Agent and Combination Therapies Against AML with Mecom Re-Arrangement (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1826;
This was consistent with previous reports that BET inhibitors (e.g., OTX015, mivebresib or ABBV-075 and JQ1) are effective against 3q26.2-r AML cell lines, patient-derived (PD) AML cells and PDX models...In follow-up experiments, XIAP/cIAPs inhibitors birinapant (10-1000 nM) or SM-164 (30-1000 nM), chosen based on the MIPE screen outcomes, induced significantly more dose-dependent apoptosis in 3q26.2-r versus the other AML cell lines...Treatment with the dual mTOR/PIK3CA inhibitor NVP-BGT226 (1-30 nM) or navitoclax or Bcl-xL-specific BH3 mimetic A-1155463 also exerted lethality and synergistically induced apoptosis with mivebresib in AML cells with inv3/t(3;3)...Co-treatment with birinapant and tegavivint also synergistically induced apoptosis in 3q26.2-r AML cells...Additionally, compared to each drug or vehicle control, co-treatment with birinapant and the BETi OTX015 (30 mg/kg/day, by oral gavage) was more effective in reducing AML burden in the xenograft model. These findings demonstrate promising preclinical activity of IAP protein inhibition against the cellular models of AML with inv3/t(3;3) with EVI1 overexpression, supporting the rationale to further evaluate in vivo efficacy of birinapant and/or BETi-based combinations against this AML sub-type.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Predictors of Cytokine Release Syndrome and Neurotoxicity in Patients with Large B-Cell Lymphoma and Their Impact on Survival (SDCC - Room 6B) - Nov 3, 2023 - Abstract #ASH2023ASH_1411; High LDH, older age and low performance score also influence the severity and onset of these outcomes. Additionally, patients who developed higher grades of CRS/ICANS and earlier onset ICANS had a higher mortality, stressing the need to develop novel strategies to mitigate the incidence and optimize management of these patients to improve their outcomes.
- |||||||||| Impact of Patient Selection and Management over Different Time Periods on the Outcome of Patients with Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy (Marriott Marquis - Pacific Ballroom) - Nov 3, 2023 - Abstract #ASH2023ASH_1299;
This retrospective analysis included all consecutive LBCL patients receiving CAR-T cell therapy (axicabtagene-ciloleucel [axi-cel] and tisagenlecleucel) in the third line setting from approval in 2019 to 2023 and reported in the Spanish Registry...The incidence of grade > or = 3 CRS and ICANS (ranging from 10% to 7% and 36% to 41%, respectively), the use of tocilizumab, corticosteroids, and anakinra as well as ICU admission rate and 12-month non-relapse mortality (2% vs 5%) remained stable across periods...The criteria for selecting patients for CAR T-cell therapy have evolved overtime towards a less aggressive disease profile and allowing less fit patients for therapy in recent times. Patients treated in the RP were more likely to respond to these therapies but this did not translate into prolonged survival or an improved safety profile.
- |||||||||| Lunsumio (mosunetuzumab) / Roche, Biogen
Cost Effectiveness of Mosunetuzumab and CAR-T Cell Therapy in Relapsed/Refractory Follicular Lymphoma (Marriott Marquis - Marriott Grand) - Nov 3, 2023 - Abstract #ASH2023ASH_1286; Patients treated in the RP were more likely to respond to these therapies but this did not translate into prolonged survival or an improved safety profile. Background: T cell engaging therapies including mosunetuzumab (mosun), a CD20/CD3 bispecific antibody, and two CAR-T cell products
- |||||||||| Jakafi (ruxolitinib) / Novartis, Incyte, CART123 / University of Pennsylvania
Cytokine Release Syndrome Results in Reduced AML Killing By CD123 CAR T Cells (SDCC - Room 6B) - Nov 3, 2023 - Abstract #ASH2023ASH_1241; Fludarabine and cyclophosphamide were used for lymphodepletion (LD)...Finally, we found that anti-apoptotic effects of cytokines can be prevented, and CART-123 killing of AML can be restored, via ruxolitinib blockade of JAK/STAT signaling in both in vitro and in vivo settings...This is in stark contrast to its role in lymphoid malignancies and underscores biological differences in myeloid versus lymphoid neoplasms. These results highlight a need to tailor therapy to limit cytokine effects on AML blasts to improve outcomes with AML-directed CAR T cell therapy.
- |||||||||| Targeting Mitochondrial Apoptotic Priming State to Personalize Therapy for Relapsed Acute Myeloid Leukemia (SDCC - Ballroom 20CD) - Nov 3, 2023 - Abstract #ASH2023ASH_947;
Overall, we demonstrate that acquired resistance to targeted therapy in AML is accompanied by common mechanism of reduction in mitochondrial priming along with drug-specific resistance mechanisms. Further, we find that, even in the context of a multiply-resistant PDX model, DBP can still identify therapeutic vulnerabilities that can be efficaciously exploited in vivo .
- |||||||||| TmMSTN-01 / Gilead
Enrollment closed, Enrollment change, CAR T-Cell Therapy: CAR T Cells in Mesothelin Expressing Cancers (clinicaltrials.gov) - Nov 2, 2023 P1, N=65, Active, not recruiting, Further, we find that, even in the context of a multiply-resistant PDX model, DBP can still identify therapeutic vulnerabilities that can be efficaciously exploited in vivo . Recruiting --> Active, not recruiting | N=27 --> 65
- |||||||||| Enrollment change: DC Vaccine in Pancreatic Cancer (clinicaltrials.gov) - Nov 2, 2023
P1, N=29, Active, not recruiting, Recruiting --> Active, not recruiting | N=27 --> 65 N=12 --> 29
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Journal, CAR T-Cell Therapy: Current and future perspectives on CAR-T cell therapy to adult malignant lymphoma (Pubmed Central) - Oct 29, 2023 To optimize CAR-T therapy under the best conditions, the treatment strategy must be decided with the referring institution in terms of T-cell fitness and tumor volume. Therefore, institutional collaboration to monitor long-term adverse events after CAR-T therapy is important.
- |||||||||| Enrollment closed: DC Vaccine in Pancreatic Cancer (clinicaltrials.gov) - Oct 27, 2023
P1, N=12, Active, not recruiting, Therefore, institutional collaboration to monitor long-term adverse events after CAR-T therapy is important. Recruiting --> Active, not recruiting
- |||||||||| Trial completion date, Trial primary completion date: DC Vaccine in Pancreatic Cancer (clinicaltrials.gov) - Oct 11, 2023
P1, N=12, Recruiting, This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious ?DC1-based strategies for patients with CRC. Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Tecartus (brexucabtagene autoleucel) / Gilead, Yescarta (axicabtagene ciloleucel) / Gilead
Journal, CAR T-Cell Therapy: Clinical Implications and Dynamics of Clonal Hematopoiesis in Anti-CD19 CAR T-cell Treated Patients. (Pubmed Central) - Oct 6, 2023 Lastly, sequential analysis showed a modest VAF increase of 1.3% and acquisition of novel mutations within 100 days postinfusion. CH was frequent in large B-cell lymphoma/ALL patients receiving CAR T-cells but did not affect toxicity nor treatment response or outcome.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis
Journal, CAR T-Cell Therapy: Outcomes of Bridging and Salvage Radiotherapy in Relapsed or Refractory Mantle Cell Lymphoma Patients Undergoing CD19-Targeted CAR T-Cell Therapy. (Pubmed Central) - Oct 3, 2023 As no studies exclusively focusing on CAR T-cell therapy and bridging or salvage RT have been published among relapsed/refractory MCL patients, our early experience underlines that using RT as a bridging and salvage approach is associated with excellent in-field control and limited toxicity in the peri-CAR T setting. Low-dose RT for MCL appears to be very effective in this highly refractory population and warrants further investigation.
|