- |||||||||| imatinib / Generic mfg.
[VIRTUAL] Progress in Ph+/Ph-like Acute Lymphoblastic Leukemia (MEETING ROOM A) - May 14, 2021 - Abstract #ICLLM2021ICLLM_68;
Combination of kinase inhibitorsagainst multiple signaling pathways may provide an opportunityfor tolerable, highly effective therapy given in addition toestablished treatment regimens. Considering the heterogeneityof lesions observed and consequently small number of patients,design of trials to demonstrate efficacy are challenging, theimplications of which will be discussed.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
[VIRTUAL] FLOW-MRD in the Era of BITE & CART Therapies (MEETING ROOM B) - May 14, 2021 - Abstract #ICLLM2021ICLLM_22;
Two CD19-targeted approaches were recentlyapproved for clinical application: the CD3/CD19 bi-specific T-cellengager, blinatumomab; and CD19-directed chimeric antigenreceptor T-cells (CD19 CAR-T cells)...On the other hand, relative expansion of CD19-negative normal very early BCPs after CD19-targetting couldlead to false-positive MFC-MRD results. Taking into accountboth changes of leukemic and normal bone-marrow cellsunder selective pressure of T-cell engagers and CAR-T, we coulddevelop cytometric approach with specificity comparable withPCR-based or NGS-based techniques with only insignificantdifferences in sensitivity.Even in the era of targeted treatment, modern multicolorapproaches allows MFC to remain the most applicable techniquefor MRD-monitoring in ALL patients.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] T-CELL SUBSET COMPOSITION AND FUNCTIONALITY IN PATIENTS WITH WALDENSTRÖM’S MACROGLOBULINEMIA. () - May 13, 2021 - Abstract #EHA2021EHA_1563;
Furthermore, cytotoxic potential of the T-cells was assessed via engagement of blinatumomab (CD3xCD19 bi-specific T-cell engager), that re-directs T-cells via CD3 to kill CD19+ tumor cells...The qualitative and quantitative changes in the immune system seen in CLL are not found in WM; T-cell numbers, distribution and functionality seem mostly preserved even in pretreated patients with a high disease burden. These findings are encouraging for the application of T-cell targeted immune therapies in WM, especially for the management of relapsed/refractory WM.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] MYTCELL': A SMARTPHONE APPLICATION GUIDES MANAGEMENT OF CAR T-CELL & BITE RELATED TOXICITIES () - May 13, 2021 - Abstract #EHA2021EHA_1413;
Background The Bispecific T-cell engager (BiTE) Blinatumomab and the CD19-specific Chimeric Antigen Receptor (CAR) T-cell products Axicabtagene-Ciloleucel and Tisagenlecleucel are approved Immunotherapies for relapsed and refractory B-cell neoplasms...Besides, “myTcell” includes an overview of the key literature and most recent publications in the field of CAR T-cells and BiTEs. Conclusion “myTcell” has the potential to become a highly usable smartphone app supporting the application of T-cell recruiting immunotherapies and the education of health care professionals. Thus, “myTcell” can increase guideline adherence, accelerate the broader and safer application of CARs and BiTEs and ultimately improve patient outcomes.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis, Vyxeos (cytarabine/daunorubicin liposomal formulation) / Jazz, Nippon Shinyaku
[VIRTUAL] A SINGLE-ARM, OPEN-LABEL PHASE 2 PILOT STUDY OF VYXEOS (CPX-351) IN ADULTS WITH RELAPSED OR REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA. () - May 13, 2021 - Abstract #EHA2021EHA_872;
Prior blinatumomab, inotuzumab, CAR-T cell therapy, and allogeneic transplant were noted in 5, 2, 1, and 2 patients...Conclusion Vyxeos in high risk refractory adult ALL was overall well tolerated and active, with median OS of approximately 6mo. A second induction course or the addition of novel agents may further improve on remission rates and duration of response.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] BLINATUMOMAB FOR HLA LOSS RELAPSE AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION () - May 13, 2021 - Abstract #EHA2021EHA_869;
By redirecting lysis of CD19-positive lymphoblast who losing the incompatible HLA, blinatumomab is a potential strategy to eradicate malignant cells via restoring GVL effects. A randomized clinical trial assessing blinatumomab in patients with HLA loss relapse after HSCT is warranted.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
[VIRTUAL] INOTUZUMAB OZOGAMICIN IN RELAPSED OR REFRACTORY ACUTE LYMPHOBLASTIC LEUKAEMIA: A REAL-WORLD RETROSPECTIVE STUDY IN THE UK () - May 13, 2021 - Abstract #EHA2021EHA_867;
At the time of InO treatment initiation, 3/19 (16%) patients had previously received blinatumomab, and 6/19 (32%) patients had undergone a prior haematopoietic stem-cell transplant (HSCT)...Conclusion In this sample of UK patients, InO was an effective treatment for patients with R/R B-cell ALL. Response rates, MRD negativity and safety profile were broadly consistent with the established profile of InO in the published phase 3 INO-VATE study.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] A PHASE II STUDY OF BLINATUMOMAB FOR THE TREATMENT OF MEASURABLE RESIDUAL DISEASE-POSITIVE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA () - May 13, 2021 - Abstract #EHA2021EHA_863;
Thirteen pts (42%) had Ph-positive ALL; 10 pts received concomitant ponatinib, 2 received dasatinib, and 1 received imatinib...The 3-year OS rates for pts with an MRD level of 0.01%>0.1% (n=10) and those >0.1% (n=21) were 72% and 60%, respectively. Conclusion Blinatumomab is well-tolerated and highly effective in eradicating MRD in pts with B-cell ALL who have persistent MRD or who experience MRD relapse.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] HETEROGENEITY OF TREATMENT RESPONSE DEFINITIONS IN REFRACTORY/RELAPSED ADULT ACUTE LYMPHOBLASTIC LEUKEMIA (R/R ALL): FINDINGS FROM A SYSTEMATIC LITERATURE REVIEW (SLR) OF CLINICAL TRIALS () - May 13, 2021 - Abstract #EHA2021EHA_862;
Inclusion criteria were applied to restrict to trials of licensed and recommended treatments for R/R aALL, i.e. blinatumomab, inotuzumab ozogamicin, tyrosine kinase inhibitors (imatinib, dasatinib, ponatinib), and chemotherapies (fludarabine-, cytarabine-, alkylator-containing regimens). Additionally, criteria were further applied to exclude clinical trials with no full-text publications that reported CR alone or both CR and CRi by search completion date...This suggests that treatment response outcome measures for historical control studies should be based on CR alone. Outcomes with comparable definitions across trials such as CR and standard efficacy measures such as overall survival are likely to provide more robust and clinically relevant cross-trial efficacy comparisons.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] FAVORABLE OUTCOMES AFTER NOVEL THERAPIES FOR RELAPSE/REFRACTORY PHILADELPHIA-LIKE ACUTE LYMPHOBLASTIC LEUKEMIA () - May 13, 2021 - Abstract #EHA2021EHA_847;
Several novel therapies such as blinatumomab (BLINA), inotuzumab (INO), CAR T cell therapy (CAR), and venetoclax-based regimens have shown promising activity in treatment of relapsed/refractory (r/r) B-cell ALL regardless of prior chemo-refractoriness or high-risk genetics; but the impact of Ph-like genotype on response to novel therapies in r/r ALL remains largely unknown...Eighteen patients (27%) received INO, 13 (19%) received CD19CAR and 4 (6%) were treated with venetoclax-navitoclax...Response rates to INO and CAR were high despite most patients in these treatment groups had prior treatment with BLINA. Integrating these novel therapies in the frontline setting could improve outcomes of Ph-like ALL and overcome their refractoriness to conventional chemotherapy.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis, Tecartus (brexucabtagene autoleucel) / Gilead
[VIRTUAL] PHASE 2 RESULTS OF THE ZUMA-3 STUDY EVALUATING KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA () - May 13, 2021 - Abstract #EHA2021EHA_471;
Median age was 40 years (range, 19–84); median bone marrow blasts at screening were 65% (range, 5–100); and 47% of patients had ≥3 prior therapies, with 45%, 22%, and 42% having previously received blinatumomab, inotuzumab ozogamicin, or allogeneic stem cell transplant, respectively...CAR T cells were undetectable by 9 months in ongoing responders. Conclusion After a median follow-up of 16.4 months, KTE-X19 demonstrated compelling clinical benefit in heavily pretreated adults with R/R B-ALL, with the median overall survival not yet reached for responding patients and a manageable safety profile.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] PRELIMINARY RESULTS OF THE GIMEMA LAL2317 SEQUENTIAL CHEMOTHERAPY-BLINATUMOMAB FRONT-LINE TRIAL FOR NEWLY DIAGNOSED ADULT PH-NEGATIVE B-LINEAGE ALL PATIENTS () - May 13, 2021 - Abstract #EHA2021EHA_468;
Methods The trial was based on the same chemotherapy backbone of GIMEMA LAL1913 (EHA 2018, #919) with two blinatumomab cycles given sequentially after early consolidation cycle 3 (high-dose methotrexate and Ara-C) and late consolidation cycle 6, respectively...Conclusion This preliminary analysis highlights the efficacy of blinatumomab added to chemotherapy in increasing MRD negativity (<10-4) in CD19+ B-lineage Ph-ALL, with the primary study endpoint fully achieved. This effect appears to translate into a lower early relapse rate and appears detectable in all risk subsets.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] UPDATED RESULTS OF THE GIMEMA LAL2116, D-ALBA TRIAL, FOR NEWLY DIAGNOSED ADULTS WITH PH+ ALL () - May 13, 2021 - Abstract #EHA2021EHA_466;
29 continued treatment with a TKI: 21 with dasatinib (85% after receiving all the 5 cycles of blinatumomab), 3 switched to imatinib due to intolerance (all after 5 cycles of blinatumomab) and 5 switched to ponatinib for a molecular increase or medical decision (66% received all 5 cycles of blinatumomab)...Among the few relapses, we observed a rather high incidence of CNS involvement. In the upcoming trial for newly diagnosed adult Ph+ ALL, CNS prophylaxis will be increased.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] DYSREGULATION OF CHROMATIN MODIFIERS DRIVES LINEAGE SWITCH IN MLL-R ACUTE LEUKEMIA () - May 13, 2021 - Abstract #EHA2021EHA_459;
Interestingly, MLLr leukemias can convert from a lymphoid CD19+ to myeloid CD19-negative phenotype, leading to antigen escape and resistance to epitope-directed therapies such as CAR-T cell or BiTE (e.g. blinatumomab) approaches...Conclusion This study shows that lineage switch in MLLr ALL can occur at multiple levels and is associated with transcriptional reprogramming including altered splicing. We propose epigenomic and spliceosome regulators as targets for future investigations and potential therapeutic approaches.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal: Blockade of VLA4 sensitizes leukemic and myeloma tumor cells to CD3 redirection in the bone marrow microenvironment. (Pubmed Central) - May 11, 2021
Redirecting T cells to specifically kill malignant cells has been validated as an effective anti-cancer strategy in the clinic with the approval of blinatumomab for acute lymphoblastic leukemia...Finally, blocking the VLA4 adhesion pathway in combination with CD3 redirection reduced the stromal-mediated inhibition of cytotoxicity and T cell activation. Our results lend support to inhibiting VLA4 interactions along with administering CD3 redirection therapeutics as a novel combinatorial regimen for robust anti-cancer responses.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Blincyto (blinatumomab) / Astellas, Amgen, Rituxan (rituximab) / Roche
Trial initiation date, Combination therapy: NCI-2021-01791: Venetoclax, Dasatinib, Prednisone, Rituximab and Blinatumomab for the Treatment of Newly Diagnosed or Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia (clinicaltrials.gov) - May 10, 2021
P1, N=20, Not yet recruiting,
Active, not recruiting --> Completed Initiation date: May 2021 --> Aug 2021
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
[VIRTUAL] Bispecific Antibodies for the Treatment of Lymphomas: Promises and Challenges (Channel 1) - May 8, 2021 - Abstract #ICML2021ICML_24;
The recent demonstration that chimeric antigen receptor (CAR) modified T cells can achieve very durable remissions in some patients with relapsed or refractory B-cell lymphomas, as well as the potential efficacy of bispecific antibodies in CAR T cell failures, has rekindled interested in bispecific antibodies as a T cell-mediated therapeutic approach. We review the early results of phase 1 clinical trials of bispecific antibodies targeting CD20 on B cells and engaging T cells via CD3 in 1:1 or 2:1 CD20:CD3 Fab formats for treatment of relapsed or refractory B-cell lymphomas.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Enrollment open, Pre-transplantation: Pediatric-type Therapy With Pre-transplant Blinatumomab for HR Patients - Phase II Study (clinicaltrials.gov) - May 7, 2021
P2, N=110, Recruiting,
We review the early results of phase 1 clinical trials of bispecific antibodies targeting CD20 on B cells and engaging T cells via CD3 in 1:1 or 2:1 CD20:CD3 Fab formats for treatment of relapsed or refractory B-cell lymphomas. Not yet recruiting --> Recruiting
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Clinical, Review, Journal: Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas. (Pubmed Central) - May 6, 2021
Several bispecific antibodies have entered early phase clinical development since the approval of the CD19/CD3 bispecific antibody, blinatumomab, for relapsed/refractory acute lymphoblastic leukaemia...We will present the currently available data from clinical trials regarding response rates, progression free survival and outcomes across a range of non-Hodgkin lymphoma subtypes. Finally, we will discuss the key toxicities of bsAbs, their rates and management of these adverse events.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Blincyto (blinatumomab) / Astellas, Amgen, Rituxan (rituximab) / Roche
New P1 trial, Combination therapy: NCI-2021-01791: Venetoclax, Dasatinib, Prednisone, Rituximab and Blinatumomab for the Treatment of Newly Diagnosed or Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia (clinicaltrials.gov) - May 4, 2021
P1, N=20, Not yet recruiting,
- |||||||||| Removab (catumaxomab) / NeoPharm, Trion Pharma, Blincyto (blinatumomab) / Astellas, Amgen
[VIRTUAL] Engineering and Functional Characterization of Anti-PSMAxCD3 Bispecific Aptamers () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_435;
Engineered bispecific aptamers are thus able to recruit effector T lymphocytes to target cells to redirect their cytolytic machinery and eliminate a particular cell population. Based on these promising properties, PSMAxCD3 aptamers have been selected for further preclinical and clinical development as prostate cancer therapeutics.
- |||||||||| otelixizumab (ChAglyCD3) / GSK, teplizumab (PRV-031) / Provention Bio, Blincyto (blinatumomab) / Astellas, Amgen
[VIRTUAL] Functional Characterization of CD3-Specific DNA Aptamers () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_434;
More recently, bispecific therapies retargeting the cytotoxic activity of effector T cells by binding to CD3 to tumors expressing tumor-associated antigen have demonstrated striking activity in patients across different cancers (blinatumomab)...Preliminary in vivo biodistribution data will also be presented. All together these lead CD3 aptamers exhibit unique properties and qualify for further preclinical and clinical development of CD3-targeting therapeutics.
- |||||||||| NVG-111 / Novalgen
[VIRTUAL] NVG-111, a novel ROR1xCD3 bispecific antibody for non-Hodgkin lymphoma. () - Apr 28, 2021 - Abstract #ASCO2021ASCO_2286;
NVG-111 shows potent T-cell mediated lymphoma cell cytotoxicity in vitro at concentrations well below those associated with extensive cytokine release . NVG-111 is in an ongoing Phase 1/2 study and may present a novel option for adoptive immunotherapy in patients with non-Hodgkin lymphoma and potentially other cancers.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
[VIRTUAL] Phase 2 results of the ZUMA-3 study evaluating KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). () - Apr 28, 2021 - Abstract #ASCO2021ASCO_1204;
P1/2
Median age was 40 y (range, 19–84), median BM blasts at screening were 65% (range, 5–100), and 47% of pts had ≥3 prior therapies, with 45%, 22%, and 42% having previously received blinatumomab, inotuzumab ozogamicin, or allogeneic stem cell transplant (alloSCT), respectively . After a median follow-up of 16.4 mo, KTE-X19 demonstrated compelling clinical benefit in heavily pretreated adults with R/R B-ALL, with the median OS not yet reached for responding pts and a manageable safety profile.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, blinatumomab subcutaneous / Amgen
Enrollment closed: A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (clinicaltrials.gov) - Apr 28, 2021
P1b, N=65, Active, not recruiting,
The regimen results in high rates of CMR and durable responses, potentially obviating the need for chemotherapy and AHSCT in many patients, particularly when used as frontline therapy. Recruiting --> Active, not recruiting
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Clinical, Journal, IO biomarker: Pediatric acute lymphoblastic leukemia. (Pubmed Central) - Apr 28, 2021
The efficacy of cellular or humoral immunotherapy has been demonstrated with the success of chimeric antigen receptor T-cell therapy and the bispecific engager blinatumomab in treating advanced disease. This review describes key advances in our understanding of the biology of ALL and optimal approaches to risk-stratification and therapy, and it suggests key areas for basic and clinical research.
- |||||||||| Darzalex IV (daratumumab) / J&J
Review, Journal, IO biomarker: Precision medicine in acute lymphoblastic leukemia. (Pubmed Central) - Apr 28, 2021
BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell, KMT2A-rearranged, Ph-positive and TCF-HLF-positive ALL, that may respond to BCL-2 inhibitor venetoclax...For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.
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