- |||||||||| Medical Crossfire (In-Person; Hybrid; Hilton Chicago, 720 S Michigan Avenue, Chicago, IL 60605, Continental Ballroom C (Lobby Level)) - Apr 26, 2024 - Abstract #ASCO2024ASCO_6945;
The experts will be challenged to defend their views with rapid-fire summaries of the latest clinical and real-world evidence. Learning Objectives Upon completion of this activity, participants will be able to: Analyze the unique MOA and safety/efficacy evidence supporting the use of CD38- and BCMA-targeting antibodies, GCPRD5-targeted agents, CAR-T therapy, and other innovative compounds across multiple myeloma treatment settings Develop personalized upfront and sequential treatment plans with innovative antibody and immunotherapy platforms, based on relevant prognostic information and safety considerations Address practical aspects of MM care when using antibody and immunotherapy platforms, including dosing, scheduling, patient referral to specialized care, education, counseling, and unique treatment-related toxicities Target Audience This educational activity is directed toward physicians, nurses, NPs/PAs, pharmacists, and other HCPs involved in the treatment of multiple myeloma.
- |||||||||| Review, Journal: Targeted therapy for multiple myeloma: an overview on CD138-based strategies. (Pubmed Central) - Apr 24, 2024
Here, our aim is to provide an overview of the most important aspects of MM disease and to investigate the molecular functions of CD138 in physiologic and malignant cell states. In addition, we will shed light on the CD138-based therapeutic approaches currently being tested in preclinical and/or clinical phases in MM and discuss their properties, mechanisms of action and clinical applications.
- |||||||||| Darzalex (daratumumab) / J&J, Tecvayli (teclistamab-cqyv) / Genmab, J&J, Talvey (talquetamab-tgvs) / J&J
Review, Journal: Targeting GPRC5D in multiple myeloma. (Pubmed Central) - Apr 12, 2024
Additionally, ongoing trials examining talquetamab in combination with agents like daratumumab and teclistamab are discussed. We offer insights into the potential utilization of various GPRC5D based therapies in the treatment paradigm for MM, either independently or in combination with established therapies.
- |||||||||| Darzalex (daratumumab) / J&J
Journal, Adverse events, Real-world evidence, Real-world: A real?world pharmacovigilance study of FDA adverse event reporting system events for daratumumab. (Pubmed Central) - Apr 11, 2024
The median onset time of daratumumab-related AEs was 11?days (interquartile range [IQR] 0-76?days), and most of the cases occurred within 30?days. Our study found potential new and unexpected AEs signals for daratumumab, suggesting prospective clinical studies are needed to confirm these results and illustrate their relationship.
- |||||||||| Darzalex (daratumumab) / J&J
Journal: Risk of new alloimmunization in patients on anti-CD38 treatment using tube LISS-IAT method. (Pubmed Central) - Apr 8, 2024
Our study found potential new and unexpected AEs signals for daratumumab, suggesting prospective clinical studies are needed to confirm these results and illustrate their relationship. Among study group there were no newly identified alloantibodies, meaning that the policy of transfusing them with matched RBCs and performing IAT/cross-matches in tube is a safe and effective policy according to the findings of this study.
- |||||||||| Ogsiveo (nirogacestat) / SpringWorks Therap, Blenrep (belantamab mafodotin-blmf) / GSK
Biomarker, Journal, IO biomarker: Soluble B-cell maturation antigen in lacrimal fluid as a potential biomarker and mediator of keratopathy in multiple myeloma. (Pubmed Central) - Apr 4, 2024
Based on the proposed mechanism, pinocytosis-induced keratopathy can be prevented by lowering the entry of sBCMA into the lacrimal fluid. Future therapeutic concepts may therefore consist of belantamab-free debulking therapy prior to belantamab consolidation and/or concomitant use of gamma-secretase inhibition as currently evaluated for belantamab and nirogacestat in ongoing studies.
- |||||||||| efbalropoendekin alfa (RG6323) / Roche
Preclinical, Journal, IO biomarker, Tumor cell: Efbalropendekin Alfa enhances human natural killer cell cytotoxicity against tumor cell lines in vitro. (Pubmed Central) - Mar 26, 2024
Because NK cells express CD38, XmAb24306 increases dara-mediated NK cell fratricide, but overall does not negatively impact the ADCC activity against a MM cell line likely due to increased NK cell activity of the surviving cells. These data show that XmAb24306 increases direct and ADCC-mediated human NK cell cytotoxicity in vitro.
- |||||||||| TNB-738 / TeneoFour, Inc, Ancora Biotech
Trial completion, Enrollment change, Trial completion date, Trial primary completion date: A Single and Multiple Dosing Study Targeting Biparatopic Antibody CD38 in Healthy Volunteers (clinicaltrials.gov) - Mar 21, 2024
P1, N=31, Completed,
It may be applicable to different antibody scaffolds for therapeutic conjugations, leading to novel targeted agents. Recruiting --> Completed | N=80 --> 31 | Trial completion date: Aug 2024 --> Jul 2023 | Trial primary completion date: Jan 2024 --> May 2023
- |||||||||| TE-1146 - T / E Pharma, Darzalex (daratumumab) / J&J
Journal: An Antibody-Drug Conjugate for Multiple Myeloma Prepared by Multi-Arm Linkers. (Pubmed Central) - Mar 13, 2024
TE-1146 precisely delivers lenalidomide to target CD38-overexpressing tumor cells. In contrast, lenalidomide without daratumumab cannot easily enter cells, whereas daratumumab without lenalidomide relies on Fc-dependent effector functions to kill tumor cells.
- |||||||||| Darzalex (daratumumab) / J&J
Treatment of Refractory Anti-NMDA Receptor Encephalitis with Daratumumab in Two Pediatric Patients (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_3546;
Second-line therapies (rituximab and cyclophosphamide) should be considered 2 weeks after first-line therapies with further escalation to an additional second-line medication or tocilizumab in refractory cases after 1-3 months. In this report, we describe two cases of pediatric anti-NMDAR encephalitis that responded to daratumumab, highlighting a potential therapeutic option to be explored in treatment-refractory cases.
- |||||||||| QL325 / Qilu Pharma
Preclinical development of QL325, a novel T cell engager targeting CLEC12A-positive AML (Section 3) - Mar 5, 2024 - Abstract #AACR2024AACR_9509;
In non-human primates, QL325 was tolerated up to 0.03 mg/kg for IV dosing and under 0.1 mg/kg for SC dosing, well above the predicted effective therapeutic dose. A phase 1 clinical trial is currently ongoing to determine the safety and early efficacy in patients with refractory or relapsed AML.
- |||||||||| XON7 / Xenothera
XON27, a novel and potent immunotherapy against hematologic malignancies (Section 6) - Mar 5, 2024 - Abstract #AACR2024AACR_5550;
Although many therapeutic advances have been made in the field of blood cancers, myeloma remains an incurable disease with a real need for new innovative therapies. XON27 represents a promising and selective immunotherapy which may provide an effective and safe treatment against refractory myeloma.
- |||||||||| Darzalex (daratumumab) / J&J, Tazverik (tazemetostat) / Eisai, Ipsen
KDM6A orchestrates NK cell response via CD38/48 regulation in multiple myeloma (Ballroom 6 B - Upper Level - Convention Center) - Mar 5, 2024 - Abstract #AACR2024AACR_3338;
Daratumumab (Dara), a first-in-class humanized monoclonal antibody targeting CD38, demonstrates notable efficacy in both newly diagnosed and relapsed/refractory multiple myeloma (MM) when administrated alone or in combination with other agents...KDM6A acts to oppose the EZH2/PRC2 complex by demethylating H3K27me3, and we found that Tazemetostat (Taze), an FDA-approved EZH2 inhibitor, increased the expression of CD38 and CD48, especially in KDM6A-KO cells...In summary, our findings illuminate the dual role of KDM6A in enhancing the efficacy of Dara in MM. Imitating KDM6A function using an FDA-approved inhibitor holds promise in overcoming Dara resistance and improving patient outcomes in MM.
- |||||||||| Tecvayli (teclistamab) / Genmab, J&J
Review, Journal: Teclistamab-cqyv in multiple myeloma. (Pubmed Central) - Feb 19, 2024
Other clinical studies are currently ongoing to investigate the association of the bispecific antibody with novel drugs with encouraging preliminary results, especially in the setting of heavily pretreated patients. In this review, the authors will provide a comprehensive overview of the drug, including its mechanism of action, major clinical trials, and future perspectives.
- |||||||||| cyclophosphamide / Generic mfg.
HAPLOIDENTICAL ALLOGENEIC CELL TRANSPLANTATION IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (ePoster area) - Feb 14, 2024 - Abstract #EBMT2024EBMT_1623;
While the effect of natural killer cell alloreactivity in haploidentical allogeneic hematopoietic cell transplantation (alloHCT) applying post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis is considered a standard treatment option in several hematologic neoplasms, it is a controversial treatment option for patients with MM... Haploidentical alloHCT with individual pre-treatment approaches and conditioning regimens induces disease control in heavily pretreated thus selected patients with r/r MM.
- |||||||||| Vyndaqel (tafamidis meglumine) / Pfizer, Darzalex (daratumumab) / J&J
PUSHING THE BOUNDARIES OF HEART TRANSPLANT AL AND WT-ATTR AMYLOIDOSIS (Hall B4-5) - Jan 26, 2024 - Abstract #ACC2024ACC_1296;
Subsequently, he exhibited a favorable response to tafamidis therapy.Case 2 A 44-year-old woman initially presented with elevated calcium levels and multiple osseous lesions detected on imaging. AL and wt-ATTR amyloidosis have received wider recognition as advancements in imaging studies allow for more precise diagnosis and treatment extending the lifespan and quality of life for patients.
- |||||||||| Darzalex Faspro (daratumumab/hyaluronidase) / J&J
Journal: Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. (Pubmed Central) - Jan 25, 2024
P3
The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma. (Funded by the European Myeloma Network in collaboration with Janssen Research and Development; PERSEUS ClinicalTrials.gov number, NCT03710603; EudraCT number, 2018-002992-16.).
- |||||||||| Journal: How I Treat Multiple myeloma in the geriatric patient. (Pubmed Central) - Jan 19, 2024
Here we present 2 patient cases derived from clinical practice. We review current frailty scores and standards of care for elderly newly diagnosed patients with MM, including frail subgroups, and discuss ways to tailor treatment as well as treatment perspectives in this population.
- |||||||||| Darzalex Faspro (daratumumab/hyaluronidase) / J&J
Daratumumab for Antibody Mediated Rejection in Lung Transplant (Board #334; Poster Hall) - Jan 9, 2024 - Abstract #ISHLT2024ISHLT_1924;
Transbronchial biopsy confirmed A1 rejection, and the patient was treated for AMR and acute cellular rejection (ACR) with pulse steroids for 3 days and plasmapheresis followed by 2 doses of IVIG and rituximab...It was decided to treat her with daratumumab subcutaneous weekly for 8 weeks...Treatment with daratumumab was well tolerated and the patient continues to have stable allograft function.Summary Daratumumab is effective in treating AMR refractory to standard therapies in lung transplant. Subcutaneous administration is well tolerated without adverse events or infectious complications.
- |||||||||| Darzalex (daratumumab) / J&J
CD38 Antibody Daratumumab as an Add-On Rescue Therapy for AMR - First Report in Clinical Lung Transplantation (South Hall 1) - Jan 9, 2024 - Abstract #ISHLT2024ISHLT_470;
Among the desensitization group, mean MFI values of all three patients decreased to 50.6%, 48.0% and 29.7% of the baseline, none of these patients developed AMR.Conclusion Targeting CD38 represents a promising addition to the AMR treatment panel. Our findings encourage the conduction of future prospective studies to further elucidate the therapeutic potential of this novel treatment approach in LTx.
- |||||||||| Retrospective data, Journal, IO biomarker: Options at the time of relapse after anti-BCMA therapy. (Pubmed Central) - Dec 17, 2023
While current data are limited to retrospective studies and small prospective cohorts, the serial use of T-cell-engaging therapies looks particularly promising, especially as BCMA-directed therapies move up earlier in the myeloma treatment course and additional CARTs and BsAbs against alternative targets (eg, G protein-coupled receptor, family C, group 5, member D and Fc receptor-homolog 5) become available. Going forward, ongoing prospective studies, large real-world data sets, and better tools to interrogate antigen expression and immune cell fitness hopefully will provide further insight into how to best individualize therapy for this difficult-to-treat population.
- |||||||||| Journal: Heavy-chain antibody targeting of CD38 NAD hydrolase ectoenzyme to prevent fibrosis in multiple organs. (Pubmed Central) - Dec 17, 2023
Here we show that treatment of mice with a non-cytotoxic heavy-chain antibody that selectively inhibits CD38 ectoenzyme resulted in NAD boosting that was associated with significant protection from fibrosis in multiple organs. These findings suggest that targeted inhibition of CD38 ecto-enzymatic activity could be a potential pharmacological approach for SSc fibrosis
- |||||||||| Review, Journal, Adverse events: A safety review of recently approved and emerging drugs for patients with relapsed or refractory multiple myeloma. (Pubmed Central) - Nov 29, 2023
We searched the published literature using PubMed, plus congress abstracts, for the above list of drug names or classes and 'myeloma.' Optimal management of toxicities associated with these recently approved and emerging therapies will be critical in maximizing clinical benefit and aiding widespread adoption in routine clinical practice. We summarize current recommendations and guidelines and provide expert insights into supportive care requirements.
- |||||||||| Review, Journal: Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. (Pubmed Central) - Nov 18, 2023
This has been driven largely by the introduction of new classes of small molecules, such as proteasome blockers (e.g., bortezomib) and immunomodulators (e.g., lenalidomide), as well as by immunotherapeutic agents starting with the anti-CD38 monoclonal antibody daratumumab in 2015...These include the bispecifics teclistamab, talquetamab, and elranatamab, and the chimeric antigen receptor (CAR) T-cell products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel)...Included in the discussion are additional monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bi- and multitargeted mAbs, and CAR T-cells and emerging natural killer (NK) cells, including products intended for "off-the-shelf" (allogeneic) applications. Emphasis is placed on the benefits of each along with the challenges that need to be surmounted if MM is to be cured.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
Journal: slan+ monocytes kill cancer cells coated in therapeutic antibody by trogoptosis. (Pubmed Central) - Nov 3, 2023
We have shown that slan+ cells infiltrate lymphomas and elicit an antibody-dependent cellular cytotoxicity (ADCC) of neoplastic B cells mediated by the anti-CD20 therapeutic rituximab...The latter findings unveil a potentially relevant contribution by slan+ monocytes in mediating the therapeutic efficacy of anti-CD47 in clinical practice, which could be particularly important when NK cells are exhausted or deficient in number. Overall, our observations shed new light on the cytotoxic mechanisms exerted by slan+ monocytes in antibody-dependent tumor cell targeting and advance our knowledge on how to expand our therapeutic arsenal for cancer therapy.
- |||||||||| Darzalex (daratumumab) / J&J, FT538 / Fate Therap
Phase I Study of FT538 + Daratumumab for Treatment of r/r AML (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6299;
P1
We hypothesized that the addition of Dara to fludarabine and cyclophosphamide would enhance lymphodepletion and augment ADCC for CD38+ AML leading to better response rates when combined with FT538. FT538 in combination with daratumumab has been tolerated in a highly pre-treated cohort of patients with expected toxicities and a signal of efficacy.
- |||||||||| Darzalex (daratumumab) / J&J
Proteomic Analysis of Monoclonal Plasma Cells from Plasma Cell Dyscrasias (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6230;
Comparison of pre- and post-treatment samples showed distinct protein expression patterns according to therapeutic agents (daratumumab and carfilzomib). The current results may contribute to the understanding of differences between each plasma cell dyscrasias and mechanisms of resistance to therapeutic agents.
- |||||||||| WVT078 / Novartis
Initial Results from a Phase 1 Dose-Escalation Study of WVT078, a BCMA (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6205;
P1
Consequently, after validation with bigger pt numbers, this novel combination may well be a very attractive frontline option for this vulnerable and difficult-to-treat pt population. Introduction: WVT078, a potent anti
|
