- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
A ROR1 specific CD3 bispecific T-cell Engager engineered for solid tumors with an expanded therapeutic window (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_1376;
In the context of JeKo1 CD19+/ROR1+ tumor targets, the 5A1 TCEs were 6-7.5 fold better decoupled compared to blinatumomab...The concentration of TCEs required for maximum IFNg release and killing of tumor cells registered in the pM range, as opposed to the supraphysiologic nM/uM range that was insufficient to induce more than 25% and 35% of IFNg release and cytotoxicity, respectively, on cells expressing <10,000 molecules of ROR1. Conclusions We hypothesize, that our ROR1 TCEs will provide a superior therapeutic index and safety profile associated with reduced risks of CRS and TLS, the capacity to dose higher, avoid continuous infusion and potentially mediate better efficacy in solid tumors.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Lunsumio (mosunetuzumab) / Roche, Biogen
EVOLVETM: a novel costimulatory T cell engager platform engineered for the treatment of immune suppressive tumors (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_1368;
We also demonstrate the modular nature of the EVOLVE platform across diverse tumor antigens including B7H4 (VTCN1), the B cell lymphoma antigen CD20 and a novel squamous tumor antigen ULBP2. Conclusions Our data highlight the broad applications of the EVOLVE platform to improve CD8 T cell-mediated anti-tumor immunity and suggest its potential as an emerging, first-in-category immunotherapeutic strategy to address unmet medical needs in oncology.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Opdivo (nivolumab) / Ono Pharma, BMS, Tecentriq (atezolizumab) / Roche
Partners for Bispecifics: combinatorial approaches to augment T-cell function and mitigate exhaustion (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_1209;
1-3 The CD19xCD3 BsAb blinatumomab was the first in class to be approved in the setting of R/R BCP-ALL with a response rate of 43%...Methods Healthy donor T cells were cocultured with CD19 + OCI-Ly1 cells and continuously stimulated with a CD19xCD3 BsAb alone or in combination with dasatinib (12.5 nM), lenalidomide (10 µg/ml), nivolumab (10 µg/ml) or atezolizumab (10 µg/ml) for 28 days...Albeit checkpoint inhibitors can boost T-cell responses, they could not ameliorate BsAb-induced T-cell exhaustion. Our data supports combinatorial approaches of BsAbs and small molecules to achieve durable T-cell responses in patients.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Clonal expansion of CD22 CAR T-cells following lentiviral vector integration in the PWWP3A gene (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_664;
P1
Background A 17-year-old female with multiply relapsed B-cell ALL following CD19 CAR T-cells and blinatumomab was treated with CD22 CAR T-cells ( NCT02315612 ) for marrow and extramedullary disease (EMD)...This trial was registered at clinicaltrials.gov as NCT02315612 . Download figure Open in new tab Download powerpoint Abstract 327 Figure 1 Frequency of T cells wherein the CAR is integrated in the PWWP3A gene and frequency of the TCRB clone post CD22 CAR T-cell infusion.
- |||||||||| onCARlytics (CF33-CD19) / Imugene, VAXinia (CF33-hNIS) / Imugene, Blincyto (blinatumomab) / Astellas, Amgen
Combination immunotherapy using a novel chimeric oncolytic virus to redirect CD19 bispecific T cell engagers to target solid tumors (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_642;
Results Tumors infected with CF33-CD19t along with blinatumomab show specific tumor cell killing in vitro and robust anti-tumor efficacy using in vivo human triple-negative breast cancer xenograft models. Conclusions Using this approach, we show that a clinically-approved CD19-directed BiTE can be combined with oncolytic viruses to activate and redirect endogenous anti-tumor immunity against solid tumors.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal: Considerations for design, manufacture, and delivery for effective and safe T-cell engager therapies. (Pubmed Central) - Oct 1, 2022
Since the approval of the CD19-targeted BiTE® (bispecific T-cell engager) molecule blinatumomab, multiple TCE molecules against different targets have been developed in several tumor types, with the approval of three additional TCE molecules in 2022...As clinical data from these molecules emerge, additional optimization of formats and manufacturability will be necessary. Ongoing efforts are focused on further improving TCE efficacy, safety, and convenience of administration.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
P2 data, Clinical Trial,Phase II, Journal, Combination therapy: ALL-424 Updated Results from the Phase II Study of Blinatumomab in Combination With Ponatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. (Pubmed Central) - Sep 29, 2022
The chemotherapy-free combination of blinatumomab and ponatinib demonstrated robust clinical activity in Ph-positive ALL, with high rates of CMR and durable remissions. This strategy will potentially obviate the need for chemotherapy and allo-SCT in many patients, particularly in the frontline setting.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Journal: EXABS-132-ALL Approach to Acute Lymphoblastic Leukemia in The Elderly. (Pubmed Central) - Sep 29, 2022
This strategy will potentially obviate the need for chemotherapy and allo-SCT in many patients, particularly in the frontline setting. No abstract available
- |||||||||| Bispecifi c Antibodies for Aggressive B-Cell Lymphoma () - Sep 22, 2022 - Abstract #SOHO2022SOHO_390;
P1, P1/2,
NCT03533283 and or mosunetuzumab, NCT03677154); and lenalidomide or the CElMoDs (NCT05169515, NCT05335018, NCT02568553)...Data from arm 1 of this study using fi rst-line epcoritamab+R-CHOP for high-risk DLBCL has demonstrated an overall response rate of 96%.2 A cohort of transplant-eligible R/R DLBCL patients who received salvage epcoritamab+R-DHAX/C with subsequent ASCT or epcoritamab monotherapy demonstrated OR and CR rates of 82.6% and 60.9%...Conclusion Clinical data indicate that BsAbs will earn a place in regular treatment of relapse aggressive lymphoma. There is broad development potential in earlier lines of therapy and as a salvage following CAR-T cell therapy.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
Approach to Philadelphia ChromosomePositive Acute Lymphoblastic Leukemia () - Sep 22, 2022 - Abstract #SOHO2022SOHO_376;
The combinations of BCR::ABL1 tyrosine kinase inhibitors (TKIs) with intensive chemotherapy, such as Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine) and other regimens, have signifi cantly improved outcomes.1 Thus, allogeneic stem cell transplantation (SCT) became an added value...The 5-year PFS rate was 81% with HyperCVAD plus ponatinib, 54% with Hyper-CVAD plus dasatinib, and 64% for Hyper-CVAD plus imatinib; and the respective 5-year OS rates were 84%, 62%, and 64%...The combination of ponatinib plus blinatumomab is highly effective (CMR rate 85%; 2-year OS rate 93%, with no relapses) and could overcome any poor-risk biology. However, longer follow-up is needed to confi rm these fi ndings.
- |||||||||| Approach to Acute Lymphoblastic Leukemia in The Elderly () - Sep 22, 2022 - Abstract #SOHO2022SOHO_375;
P3
At the time of relapse, some may respond to “TKI escalation” to a second-generation agent such as dasatinib (if initially treated with imatinib), or ponatinib.8-10 For older adults eligible for low-intensity chemotherapy, the European ALL Working Group (EWALL) studies of a TKI (dasatinib – EWALL-PH01; nilotinib – EWALLPH02) plus low-intensity chemotherapy for patients 55 years have shown encouraging OS, particularly in the latter EWALL-PH02 study where a signifi cant proportion of patients subsequently received an allogeneic hematopoietic stem cell transplant (alloHSCT).11,12 Ongoing investigation focuses on developing therapeutic schemes able to induce deeper and more durable remissions, with less toxicity...Other studies are investigating ponatinib plus blinatumomab for both induction and consolidation, ponatinib plus venetoclax, and dual TKI treatment with dasatinib and asciminib (combining an ATP binding site and an allosteric inhibitor of ABL).14-16 It is remarkable that the once-feared Philadelphia chromosome is a welcome result in the evaluation of an older adult with ALL...Inotuzumab ozogmacin has been a favored approach for inducing remissions in older adults with ALL given its effi cacy in setting of high disease burden.25 In contrast, blinatumomab appears to be more effective for minimal residual disease.26 The US SWOG 1318 study employed blinatumomab for both induction and consolidation and reported a CR rate of 66% which is notably lower than reported by the InO-based studies.27 Another promising agent is the BCL-2 inhibitor venetoclax, an agent with pre-clinical effi cacy as a single agent in lymphoid diseases including ALL.28,29 Venetoclax is being tested with mini-hyper-CVD in an ongoing phase 1/2 study.30 In the phase 1 portion of the study, among adults 60 years with newly diagnosed disease, 10 of the fi rst 11 patients treated achieved an MRD-negative remission allowing 9 patients to bridge to alloHSCT...Still, ALL remains a complex disease, with complicated treatment considerations particularly in individuals balancing ALL in the context of co-morbid conditions and frailty. Referral to academic centers for consideration of a clinical trial enrollment is strongly encouraged (see Table 1 for select clinical trials).
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Opdivo (nivolumab) / Ono Pharma, BMS, Yervoy (ipilimumab) / Ono Pharma, BMS
Review, Journal: Neurology of cancer immunotherapy. (Pubmed Central) - Sep 20, 2022
Referral to academic centers for consideration of a clinical trial enrollment is strongly encouraged (see Table 1 for select clinical trials). In this article, we describe the most frequently reported NAEs and aim to give neurologists a practical overview on how to deal with them.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal: Treatment of Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia-From Intensive Chemotherapy Combinations to Chemotherapy-Free Regimens: A Review. (Pubmed Central) - Sep 20, 2022
Second-generation TKIs combined with intensive or low-intensity chemotherapy resulted in higher CMR rates compared with imatinib-based regimens...To further improve the outcomes, the potent third-generation TKI ponatinib was added to chemotherapy...The recent chemotherapy-free combination of dasatinib and blinatumomab was safe and effective in patients with newly diagnosed Ph-positive ALL and resulted in an estimated 3-year OS rate of 80%; 50% of patients underwent allogeneic SCT...The promising results obtained with the chemotherapy-free regimens of blinatumomab plus TKIs question the role of allogeneic SCT in first remission. Patients with Ph-positive ALL who achieve early and deep molecular responses have excellent long-term outcomes and may not benefit from allogeneic SCT.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, AMG 562 / Amgen
Journal: T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals. (Pubmed Central) - Sep 14, 2022
In an in vitro model system, mimicking 28-day continuous infusion with the half-life-extended CD19xCD3 bispecific AMG 562, we identified hallmark features of exhaustion arising over time...Our data demonstrate the relevance of T-cell exhaustion in bispecific antibody therapy and highlight that T cells can be functionally and transcriptionally rejuvenated with TFIs. In view of the growing number of bispecific molecules being evaluated in clinical trials, our findings emphasize the need to consider and evaluate TFIs in application schedules to improve clinical outcomes.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal: Severe infections in recipients of cancer immunotherapy: what intensivists need to know. (Pubmed Central) - Sep 10, 2022
Moreover, we recommend that the wide use of these Mabs depends on designing further cost-effectiveness trials in this field. Chimeric antigen receptor T-cell therapy is associated with profound immunosuppression and the risks of bacterial, fungal and viral infections vary according to the time since infusion.Immune checkpoint blockers are associated with an overall favorable safety profile but associations of checkpoint blockers and corticosteroids and immunosuppressive drugs prescribed to treat immune-related adverse events are associated with increased risks of bacterial and fungal infections.The T-cell engaging bispecific therapy blinatumomab causes profound B-cell aplasia, hypogammaglobulinemia and neutropenia, but seems to be associated with fewer infectious adverse events compared with standard intensive chemotherapy.Lastly, intravesical administration of Bacillus Calmette-Guérin (BCG) can lead to disseminated BCGitis and severe sepsis requiring a specific antibiotherapy, often associated with corticosteroid treatment.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal, IO biomarker: CRLF2 Gene in B-cell Acute Lymphoblastic Leukemia. (Pubmed Central) - Sep 8, 2022
Blinatumomab is an available immunotherapy, and there are currently a few ongoing clinical trials to treat CRLF2 B-ALL. This review focuses on the role of CRLF2 in B-ALL and summarizes the literature regarding its molecular pathways, clinical significance, incidence rates across demographics, therapies, and areas of further research.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Trial completion date, Trial primary completion date: SWOG-S1318: Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia (clinicaltrials.gov) - Sep 7, 2022
P2, N=57, Active, not recruiting,
This review focuses on the role of CRLF2 in B-ALL and summarizes the literature regarding its molecular pathways, clinical significance, incidence rates across demographics, therapies, and areas of further research. Trial completion date: Jun 2023 --> Sep 2023 | Trial primary completion date: Jun 2023 --> Jun 2022
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal: Outcomes of Allogeneic Hematopoietic Cell Transplantation in Adults with Fusions Associated with Ph-like ALL. (Pubmed Central) - Sep 2, 2022
Compared with other non-Ph-like ALL (n = 71), patients with fusions associated with Ph-like ALL were more frequently Hispanic (P = .008), were less likely to carry high-risk cytogenetics (P < .001), and were more likely to receive blinatumomab prior to HCT (P = .019)...Relapse rate was associated with disease status (P=0.028) and conditioning regimen intensity (P=0.028). In conclusion, our data suggest that alloHCT consolidation results in similarly favorable survival outcomes in adult patients with Ph-like fusions and other high-risk B-cell ALL.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal, PD(L)-1 Biomarker, IO biomarker: A phase two study of high dose blinatumomab in Richter's syndrome. (Pubmed Central) - Aug 31, 2022
P2
The patient who achieved CR had the lowest levels of immune checkpoint expression. Simultaneous targeting with immune checkpoint blockade, especially PD1 inhibition, which has already demonstrated single-agent efficacy in RS, could achieve synergistic killing and enhance outcomes.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Journal: Mini-hyper CVD + CRIB (condensed rituximab, inotuzumab ozogamicin, and blinatumomab) for refractory pediatric B-acute lymphoblastic leukemia. (Pubmed Central) - Aug 30, 2022
This regimen was well tolerated, and he received his transplant and engrafted with no significant infections, toxicities, or sinusoidal obstruction syndrome. This is the first reported use of a condensed sequential immunotherapy/chemotherapy regimen in a pediatric leukemia patient.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal: Robust immune responses to SARS-CoV-2 in a pediatric patient with B-Cell ALL receiving tisagenlecleucel. (Pubmed Central) - Aug 27, 2022
The T-cell response was polyfunctional and predominantly CD4 restricted. This data has important implications for the understanding of SARS-CoV-2 immunity in patients with impaired immune systems and the potential application of SARS-CoV-2-specific T-cell therapeutics to treat patients with blood cancers who receive B cell depleting therapy.
- |||||||||| Monjuvi (tafasitamab) / MorphoSys, Xencor, Incyte, Specialised Therap, Blincyto (blinatumomab) / Astellas, Amgen, Zynlonta (loncastuximab tesirine) / Overland ADCT BioPharma, Mitsubishi Tanabe, SOBI
Review, Journal: Targeting CD19 for diffuse large B cell lymphoma in the era of CARs: Other modes of transportation. (Pubmed Central) - Aug 24, 2022
We explore the emerging evidence that CD19 expression is retained following exposure to these agents and that patients can be successfully re-challenged with anti-CD19 therapies of a different drug class upon disease relapse post-CAR T cells. Finally, we discuss how these drugs potentially fit into the most current treatment paradigm for DLBCL.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal: Feasibility of ovarian stimulation for fertility preservation during and after blinatumomab treatment for Ph-negative B-cell acute lymphoblastic leukemia. (Pubmed Central) - Aug 24, 2022
The first patient was a 30-year-old woman with relapsed Ph-B-ALL who received prednisolone (PSL) and cytoreductive chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone, followed by three courses of blinatumomab bridging to allo-HSCT...The second patient was a 26-year-old woman with newly diagnosed Ph-B-ALL who received PSL, one course of conventional chemotherapy, and one course of high-dose methotrexate and cytarabine followed by two courses of blinatumomab bridging to allo-HSCT...Use of a 2-week rest period enabled ovarian stimulation and oocyte retrieval to be performed without delaying treatment. Blinatumomab may be an option for preserving fertility while maintaining treatment intensity.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Journal: Multicenter comparison of first salvage chemotherapy versus novel therapy regimens in adult relapsed/refractory acute lymphoblastic leukemia. (Pubmed Central) - Aug 24, 2022
However, this study has several limitations including younger age, increased CNS involvement, and higher blast percentage in the chemotherapy arm and potential confounders, including selection of treatment sequence as 43 patients (55.8%) ultimately received both chemotherapy and novel therapy. Therefore, a larger, prospective, randomized study with adequate chemotherapy comparators and availability of novel agents upon relapse is warranted to confirm these results.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal: Blinatumomab as bridging therapy in paediatric B-cell acute lymphoblastic leukaemia complicated by invasive fungal disease. (Pubmed Central) - Aug 24, 2022
Blinatumomab, a bispecific T-cell engager targeting cells expressing CD19, has shown promise for treatment of relapsed/refractory B-cell acute lymphoblastic leukaemia (B-ALL) and is associated with reduced toxicity compared to conventional chemotherapy. With close monitoring of minimal residual disease, we demonstrate that children with B-ALL can receive repeated cycles of bridging blinatumomab whilst conventional chemotherapy is withheld during treatment and recovery from IFD.
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