- |||||||||| Nplate (romiplostim) / Amgen
The (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4175;
Normalization of the platelet clearance rate before tapering may be indicative of reaching remission in individual cases. Although more research into the underlying mechanisms leading to immune modulation is needed, these observations can be useful to identify patients who may benefit from TPO-RA treatment and subsequent tapering.
- |||||||||| vevoctadekin (ST-067) / Simcha Therap
Preclinical Efficacy of Decoy-Resistant IL-18 in Hematological Malignancies (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3885;
P1, P1/2
Conclusion : These studies extend the efficacy of DR-18 therapy in hematologic malignancies and demonstrate the potential benefit of combining DR-18 with additional agents beyond anti-PD-1, including chemotherapy and T cell engagers. These findings strengthen the rationale for expanding the use of the Phase I human DR-18 cytokine (ST-067, NCT04787042 & NCT06492707) in combination therapies for patients with hematological tumors.
- |||||||||| ASTX295 / Otsuka
ASTX295 a Novel Potent MDM2 Antagonist Induces More Than One Mechanism of Programmed Cell Death (PCD) in Lymphoid Malignancies (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3881;
P1/2
Previous studies have shown in vitro activity in acute myeloid leukemia both alone and in combination with decitabine...Activity of ASTX295 was compared with AMG232 and Idasanutlin...ASTX295 in combination with the specific BCL2 inhibitor Venetoclax in the GRANTA519 cell line (CI value 0.2) and KARPAS384 (CI value 0.4) demonstrated strong synergy, despite as monotherapy resulting in <50% fall in viability...ASTX295 like other MDM2i showed synergy with BCL2i in DLBCL and MCL models. ASTX295 induced multiple forms of PCD; the precise form of non-caspase dependent PCD remains under investigation.
- |||||||||| Aucatzyl (obecabtagene autoleucel) / Autolus
Risk Factors Associated with Sub-Optimal Outcomes Following Obecabtagene autoleucel (obe-cel) for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL): What We Have Learned from the FELIX Trial (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3862;
P1/2
Pts received bridging therapy as appropriate and underwent lymphodepletion (LD; fludarabine, 4x30mg/m2; cyclophosphamide, 2x500mg/m2), followed by tumor burden-guided infusions on Days 1 and 10 to a target dose of 410x106 CAR T-cells...Baseline characteristics were generally similar across the two groups but a higher proportion of pts were male in the low-risk group vs the high-risk group (72% vs 47%), with increased rates of pre-treatment in low-risk pts vs high-risk pts : ?3 prior therapies (48% vs 32%); previous allo-stem cell transplant (allo-SCT; 56% vs 41%), and previous inotuzumab ozogamicin or blinatumomab (80% vs 51%)...Pts with high-risk HT scores had consistently worse outcomes than pts with low-risk HT scores. Further studies are warranted.
- |||||||||| CD22/CD19 CAR T / The First Affiliated Hospital of Soochow University
Safety and Efficacy of CD22/ CD19 CAR-T and Auto-HSCT (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3857;
P1/2
Further studies are warranted. Afterwards, autologous CAR T-cells targeting CD22 and CD19 (CAR-T 1, co-stimulatory molecule was 4-1BB and infusion dose was 5
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Outcomes of Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia Given Blinatumomab As Last Consolidation Treatment before Allogeneic Hematopoietic Cell Transplantation (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3389;
Twenty-six relapsed patients received Inotuzumab Ozogamicin (InO) as part of the reinduction strategy prior to blinatumomab...Patient transplanted from matched related (n=13) and unrelated donor (UD, n=33) received unmanipulated bone marrow or peripheral blood stem cells (PBSC) grafts with conventional cyclosporin-A and short-term MTX GvHD prophylaxis...Results obtained in CR1 support the incorporation of blinatumomab bridging in all subjects with a transplant indication after first-line therapy. For CR2/3 patients, sequential targeting of CD22 and CD19 with InO and blinatumomab before HCT offers excellent DFS probabilities.
- |||||||||| Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Still You Hesitate to Use Ino?: Inotuzumab Ozogamicin Optimized Post-Transplant Outcomes in R/R Ph-Negative B-ALL (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3380;
The standard chemotherapy (SC) group was defined to include patients who received neither InO nor blinatumomab (Blina)...All patients received SOS-specific treatment including defibrotide or recombinant human thrombomodulin...ConclusionOur results encourage the salvage chemotherapy with InO before allogeneic HCT especially in Ph-negative R/R B-ALL patients. Compared to SC, InO had a higher remission induction rate, better post-transplant prognosis, and controllable post-transplant SOS.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Short-Term Blinatumomab Prior to Allo-HSCT for High-Risk B-ALL (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3312;
In addition, short-term BiTE treatment pre-HSCT increase neither the risk of infections in the para-transplantation period(P=0.810), nor the incidences of cytomegalovirus (CMV)(P=0.823), Epstein-Barr virus (EBV)(P=0.800) infections post-HSCT. Conclusions : Short-term BiTE before BUCY conditioning regimen could improve the OS and EFS of high-risk B-ALL compared with BUCY regimen, and was likely to lower the incidence of aGVHD.
- |||||||||| Neupogen (filgrastim) / Kyowa Kirin, Amgen, Rituxan (rituximab) / Roche
TCR?/? Depleted Mobilized Pbscs without Calcineurin Inhibitors in Patients with Fanconi Anemia (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3308;
P2
T cells/kg recipient weight (n=4)...Analysis of gd T cell proportions at 6 months (16.2% vs 3.2%, p = 0.0106; TCRa/b PBSC vs. CD34 selection) indicated that TCRa/b depletion resulted in a lasting immune imprint, underpinning the differences in reconstitution between these two transplant methodologies. Conclusions : TCRa/b depleted PBSC transplantation without CNI results in excellent engraftment, minimal GVHD, few viral infections and excellent survival in FA patients with promising outcomes in those with hematologic malignancy, biallelic BRCA2 genotype and older age who historically often did poorly.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Efficacy and Safety of Donor Lymphocyte Infusion after Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3276;
We successfully added ponatinib to DLI in one patient with CML who became BCR-ABL fusion transcript positive after HSCT...One of them who suffered from relapsed JMML before HSCT received azacytidine in addition and another patient with pulmonary relapse of Ewing sarcoma before HSCT received zoledronic acid additionally...We administered sorafenib in addition to DLI in two patients with relapsed AML and achieved molecular remission in both cases...We increased the DLI doses gradually and observed a very low rate of GVHD. Therefore, we consider DLI as a safe and highly effective therapeutic option to enhance GVL effect and increase donor chimerism.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Ibrance (palbociclib) / Pfizer
Combination with Palbociclib Overcomes Venetoclax Resistance Mechanisms and Outperforms Single Agent Efficacy in Acute Myeloid Leukemia (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2708;
Introduction : Initial remission rates for acute myeloid leukemia (AML) patients treated with venetoclax (ven) plus azacytidine have been promising (Di Nardo et al, 2019), however, drug resistance and disease relapse continue to be a major hurdle mitigating long-term treatment and overall survival...Interestingly, loss of BAX led to enhanced sensitivity to palbo as well as abemaciclib, another FDA approved CDK4/6 inhibitor, indicating CDK4/6 inhibitors could be beneficial treatments for patients who have acquired ven resistance via BAX mutation...A greater understanding of the ven+palbo efficacy and mechanisms of resistance has helped to inform the subsets of patients who may benefit from treatment with ven+palbo as well as identify additional therapies that may boost efficacy and mitigate resistance. This study provides a promising therapeutic strategy for improving the long-term treatment and survival of AML patients and highlights novel potential drug repurposing : AXL inhibitors to treat AML patients harboring an IKZF1 mutation; CDK4/6 inhibitors for AML with BAX mutation.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Addition of Blinatumomab to Consolidation Therapy Among Older Newly Diagnosed Patients (pts) with BCR::ABL1 Negative B-Lineage Acute Lymphoblastic Leukemia (ALL) in the ECOG-ACRIN E1910 Randomized Phase III Trial (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2668;
In E1910, exposure to dexamethasone and pegasparagase was reduced for older pts (age >55 years)...Methods Details of the E1910 protocol remission induction (step 1), high dose methotrexate with pegaspargase intensification (step 2), blina randomization (step 3), and maintenance (step 4) or allogeneic hematopoietic stem cell transplant (HCT) were previously presented (Litzow, NEJM 2024)...Comparison of OS and RFS between treatment arms was conducted using the two-sided stratified log-rank test and Cox model with CD20 status, rituximab use, and whether pts intended to receive HCT or not as stratification factors...This is possibly due to sample size but may be due to biologic differences in the older adult population. Further studies are needed to definitively determine tolerance and benefit of blina addition to consolidation for older pts with ALL.
- |||||||||| Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Extended Follow-up of Dose-Adjusted EPOCH (DA-EPOCH) Plus Inotuzumab Ozogamicin (InO) in Adults with Relapsed/Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (B-ALL): A Safe and Effective Salvage Therapy (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2666;
P1
We have shown that DA-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) plus InO (DA-EPOCH-InO) elicits high response rates with a favorable safety profile in a phase I study in R/R B-ALL (Kopmar et al., JAMA Oncol, 2024)...All pts received ursodiol and anti-infective prophylaxis...With a median follow-up among survivors of 21.7 months (m), the median OS was 17.0 m, and the median EFS was 10.0 m. Among responders, 18 (67%) received consolidative imtx while in remission (i.e., HCT, CAR-T, or blinatumomab), with HCT used in 12 pts (44%)...It also allows administration of InO in an outpatient setting, an important practical consideration. Overall, these data support both the current use and further development (e.g., as frontline therapy) of this regimen for pts with B-ALL.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
CD19 CAR-T Therapy for Patients with Relapsed or Refractory Philadelphia Chromosome (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2658;
The median number of prior treatment lines was 6 (range 2-20), with 35 (43.8%) patients having been exposed to ?2 TKIs, 5 (6.2%) having received prior blinatumomab, and 17 (21.3%) having undergone prior allo-HSCT...In addition, CAR-T treatment bridging transplantation as consolidation therapy may suggest improved long-term survival. This analysis underscores the promise of CAR-T therapy as a viable treatment option for R/R Ph+ ALL.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Tecartus (brexucabtagene autoleucel) / Gilead, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
NGS MRD Negativity on Day 28 after Brexu Cel in Adults with R/R ALL Is Associated with Favorable Progression Free Survival (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2657;
Introduction : Brexucabtagene autoleucel (brexu cel) is a CD19-targeted chimeric antigen receptor (CAR) T cell therapy approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL)...No differences were observed with respect to sex, TP53 mutation status, prior inotuzumab (ino) or blinatumomab (blina) exposure, disease burden prior to CAR, or development of any cytokine release syndrome (CRS) or any neurotoxicity with brexu cel...Similar results have been obtained in pediatric ALL patietns ftreated with 41BB-based tisagenleucleucel (Pulsipher et al., Blood Cancer Discovery 2022). Longer follow-up is needed to validate the safety of omitting consolidative HCT in such pts, but these results encourage the potential for definitive therapy with brexu cel when D28 ClonoSeq NGS MRD is negative.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, navitoclax (ABT 263) / AbbVie
A Phase I/II Study of Mini-Hyper-CVD, Venetoclax and Navitoclax in Patients with Relapsed/Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2655;
Pts with CD20+ ALL also received up to 8 doses of rituximab...Among the 12 pts with B-cell ALL, all had received prior blinatumomab and 9 (75%) had received prior inotuzumab ozogamicin; among the 10 pts with T-cell ALL/LBL, 5 (50%) had received prior nelarabine...Notably, all 3 pts with R/R ETP ALL achieved CR. While response rate and survival appear better than historical expectations with chemotherapy alone in this population, these outcomes appear similar to those achieved with mini-hyper-CVD + venetoclax in a similar cohort of pts with R/R Ph- ALL (Short NJ et al Blood Adv 2023), questioning the benefit of adding a Bcl-xL inhibitor to this regimen.
- |||||||||| Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Phase II Study of Inotuzumab Ozogamicin for the Treatment of Measurable Residual Disease-Positive B-Cell Acute Lymphoblastic Leukemia: 3-Year Update (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2651;
1x10-6 when applicable All patients received ursodiol for hepatic sinusoidal obstruction syndrome (SOS) prophylaxis...Seventeen patients (57%) had received prior blinatumomab...SOS was seen in three patients : one pt with Ph-negative ALL developed SOS 2 weeks following transplant (recovered after defibrotide therapy), and two pts both with Ph-positive ALL on concurrent ponatinib (of whom one died). Conclusion : INO resulted in high survival and MRD negativity rates in most patients with B-cell ALL and persistent MRD or MRD recurrence, with a favorable safety profile.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Blincyto (blinatumomab) / Astellas, Amgen
Efficacy of Combination Blinatumomab and Ponatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) and Chronic Myeloid Leukemia in Lymphoid Blast Phase (CMLBP) in a Real World Setting (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2639;
TKD mutations were seen in 5/8 (T315I (n=2), V299L, E292Q, and T315I+E255K); all but E292Q were associated with exposure to dasatinib...Among 11 responders, 4 had alloSCT, 2 moved to other therapy for symptomatic vascular disease (CAR, Bosutinib), and 5 proceed to mP; 3 relapsed on mP, all in the CNS...AlloSCT consolidation in responding patients did not appear to confer any OS benefit relative to mP. Finally, among those with sustained molecular remission of at least 2y, discontinuation of TKI may be feasible.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Blinatumomab with De-Escalated Chemotherapy for Infant KMT2A-Rearranged B-Cell Acute Lymphoblastic Leukemia (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2635;
Medium risk (MR) patients were all other patients and proceeded to a second cycle of blinatumomab, followed by delayed intensification with OCTADAD (dexamethasone, vincristine, daunorubicin, pegylated asparaginase, cyclophosphamide and cytarabine) and oral maintenance with removal of MARMA block (high dose cytarabine, high dose methotrexate, pegylated asparaginase)...For HR patients, there is a 96% reduction in cytarabine (from 26520 to 1050 mg/m2), a 66% reduction in pegylated asparaginase (from 3000 to 1000 iu/m2), and completely removes high dose methotrexate, cyclophosphamide and 6-mercaptopurine...Given most patients relapse within the first 18 months, our initial survival rates are encouraging. We plan to further reduce induction intensity by removing cytarabine and anthracycline for all patients and reducing induction to 15 days in patients who have achieved MRD <5% who are suitable to receive blinatumomab at this level of disease.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Chemotherapy Free Regimen of Inotuzumab Ozogamicin and Blinatumomab in Frontline Therapy of Older Patients with Philadelphia Negative B-Cell Acute Lymphoblastic Leukemia (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2618;
Treatment consisted of Dexamethasone intravenous (IV) 20 mg (Day) D1-D4 and vincristine 1 mg IV on D4 with fractionated InO 0.6 mg/m2 on D1 and 0.3 mg/m2 on D8, in Cycle (C) 1...CNS prophylaxis with alternating IT methotrexate and cytarabine was administered for 12 doses...All pts received ursodeoxycholic acid prophylaxis...11 pts (79%) received rituximab...Conclusion : A chemotherapy minimized combination of InO and Blina leads to promising response and survival outcomes in older pts with newly diagnosed B-ALL and appears tolerable. Longer follow up to assess safety, continued efficacy and incidence of secondary myeloid neoplasms is needed in this population.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Low Intensity Mini-Hypercvd (mHCVD), Inotuzumab Ozogamicin (Ino) with/without Blinatumomab (Blina) in Older Patients with Newly Diagnosed Philadelphia Negative B-Cell Acute Lymphoblastic Leukemia (B-ALL): 10 Years Update (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2617;
12 doses of intrathecal IT MTX /cytarabine were given for CNS prophylaxis; pts with CNS disease had IT hydrocortisone, MTX, and cytarabine 2/week till CNS clearance, then weekly x 4. 8 doses of rituximab 375mg/m2 were given on D1, 8 of C1-4 if CD20 was ?20% by flow cytometry (FCM)...Ursodeoxycholic acid was given to all pts...Maintenance was initially with vincristine 2mg D1, prednisolone 50mg daily D1-5, 6-mercaptopurine 50mg BID & MTX 10mg/m2 weekly (POMP) for 3 years...Conclusion : mHCVD-InO
- |||||||||| blinatumomab subcutaneous / Amgen
Single-Agent Subcutaneous Blinatumomab for Advanced B-Cell Acute Lymphoblastic Leukemia: Long-Term Follow-up from a Phase 1b Dose Expansion Cohort (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2616;
P1/2
8 doses of rituximab 375mg/m2 were given on D1, 8 of C1-4 if CD20 was ?20% by flow cytometry (FCM)...Ursodeoxycholic acid was given to all pts...Maintenance was initially with vincristine 2mg D1, prednisolone 50mg daily D1-5, 6-mercaptopurine 50mg BID & MTX 10mg/m2 weekly (POMP) for 3 years...Conclusion : mHCVD-InO Of these, 9 pts (33%) were primary refractory, 8 pts (30%) had relapsed after prior HSCT, 4 pts (15%) had relapsed after prior CD19 CAR T
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Updated Results from a Phase II Study Hyper-CVAD, with or without Inotuzumab Ozogamicin, and Sequential Blinatumomab in Patients with Newly Diagnosed B-Cell Acute Lymphoblastic Leukemia (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2615;
Pts with CD20+ disease (?1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2)...Beginning with pt #39, INO at a dose of 0.3 mg/m2 on day 1 and 8 was added to the 2 cycles of MTX/Ara-C (dose reduced to 500 mg/m2 of MTX and 1 g/m2 of Ara-C) and to 2 cycles of blinatumomab consolidation (4 total cycles with INO)...Conclusion In pts with newly diagnosed Ph-negative B-ALL, the addition of INO to the hyper-CVAD + blinatumomab appears to improve OS. To confirm these findings, this study now randomizes pts to hyper-CVAD + blinatumomab
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