CD38-targeted antibody-drug conjugate 
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  • ||||||||||  Blenrep (belantamab mafodotin) / GSK
    Retrospective, single-center, real-world experience of belantamab mafodotin in relapsed/refractory multiple myeloma. (Available On Demand; 483) -  Apr 28, 2022 - Abstract #ASCO2022ASCO_4172;    
    Our current study in heavily pretreated RRMM pts, of whom the majority would have been ineligible for the DREAMM-2 study, demonstrates an ORR, PFS, and ocular AE profile with SOC belamaf therapy comparable to outcomes reported in the pivotal registration study. Future studies are needed to further define the optimal use and sequencing of belamaf in MM pts, particularly in context of other BCMA-targeting modalities.
  • ||||||||||  WITHDRAWN: CD38 AND LRG1 DRIVE DIFFUSE TYPE GASTRIC CANCER PROGRESSION VIA TUMOR STROMAL REMODELING. (28DE - San Diego Convention Center) -  Apr 25, 2022 - Abstract #DDW2022DDW_3816;    
    Conclusion Diffuse type gastric cancer forms tumor progression circuit with angiogenesis and fibrosis by expressingDGC tumors carrying mutations in Cdh1 and Tgfbr2 genes express high levels of CD38 and Lrg1, which contribute to tumor invasion by remodeling tumor microenvironment. Treatment targeting these genes could be an option for personalized medicine against DGCs carrying these gene mutations, suggesting the possibility that CD38 and CD105 are new therapeutic target of DGC.
  • ||||||||||  Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
    Review, Journal, IO biomarker:  Targeted inhibitors and antibody immunotherapies: Novel therapies for paediatric leukaemia and lymphoma. (Pubmed Central) -  Apr 22, 2022   
    Considering the number of oncology medicinal products available for adults and the rarity of paediatric cancers, prioritisation based on scientific evidence and medical need, as well as international collaboration, is critical. Herein, we review the current status of drug development for children with leukaemia and lymphoma, excluding cellular therapy despite its well-known significance.
  • ||||||||||  Review, Journal:  Novel therapies for immune thrombocytopenia. (Pubmed Central) -  Apr 21, 2022   
    This review will focus on these novel mechanisms for treating ITP and assess the status of treatments currently under development. Successful new treatments for ITP might also provide a pathway to treat other autoimmune disorders.
  • ||||||||||  Darzalex (daratumumab) / J&J, Carvykti (ciltacabtagene autoleucel) / J&J
    BCMA CAR-T AFTER ALLOGENEIC HCT INDUCES REMISSION IN REFRACTORY PLASMABLASTIC LYMPHOMA () -  Apr 20, 2022 - Abstract #ASPHO2022ASPHO_87;    
    P1b
    Once GVHD was quiescent with steroids and tacrolimus, the patient began fludarabine and cyclophosphamide conditioning with persistent disease... Our data support consideration of BCMA CAR-T for refractory PBL, which has high mortality, which was well-tolerated and induced a remission in this multiply refractory patient.
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Review, Journal:  Updates in the Management of Warm Autoimmune Hemolytic Anemia. (Pubmed Central) -  Apr 20, 2022   
    While splenectomy and a number of immunosuppressive therapies have been used in the setting of relapsed and refractory disease, the optimal choice and sequence of therapies is unknown, and clinical trials should be offered when available. Newer investigational targets include spleen tyrosine kinase inhibitors, monoclonal antibodies targeting CD38, Bruton's tyrosine kinase inhibitors, complement inhibitors, and antibodies against neonatal Fc receptors.
  • ||||||||||  STI-6129 / Sorrento
    Phase classification:  Study to Assess Anti-CD38 Antibody Drug Conjugate in Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) -  Apr 14, 2022   
    P1b/2a,  N=72, Recruiting, 
    Newer investigational targets include spleen tyrosine kinase inhibitors, monoclonal antibodies targeting CD38, Bruton's tyrosine kinase inhibitors, complement inhibitors, and antibodies against neonatal Fc receptors. Phase classification: P1 --> P1b/2a
  • ||||||||||  Darzalex IV (daratumumab) / J&J
    Journal:  Daratumumab in AL Amyloidosis: A Real-Life Experience of the "RTM" (Regional Tuscan Myeloma Network). (Pubmed Central) -  Mar 26, 2022   
    Patients were treated at relapsed/refractory disease stages (n = 29) with a median of one previous line of therapy or at diagnosis (n = 4). Daratumumab showed good efficacy, representing 60% of good hematological responses and 50% of organ responses in a real-life population of patients with an acceptable toxicity profile.
  • ||||||||||  Genetic evolution: Druggable MM therapeutics: Pathogenetic pathways ([VIRTUAL]) -  Mar 26, 2022 - Abstract #EMN2022EMN_26;    
    Another important target is the E3 ubiquitin ligase CRBN, and in fact, two CELMoDs (CRBN modulators), Iberdomide (CC-220) and CC-92480, have demonstrated activity (ORR 30-50%) and a favorable safety profile in heavily pretreated patients...Other approaches are also attractive such as myc inhibition or additional ways of activating the immune system. In this last field, two novel mechanisms hold significant promise: inhibition of the do not eat me signal with anti-CD47 MoAb such as Magrolimab, or the use of Modakafusp a CD38 MoAb with two IFN attenuated molecules that induces a anti-tumoral One important field of investigation is the search for biomarkers predicting sensitivity or resistance to a given agents, such as venetoclax in t(11;14) patients, Mcl-1 inhibitors in patients with 1q+, or RAS/RAF/MEK inhibitors for patients with activation of this pathway.
  • ||||||||||  STI-6129 / Sorrento
    Trial completion date, Trial primary completion date:  Study of the Safety and Efficacy of STI-6129 in Patients With Relapsed or Refractory Systemic AL Amyloidosis (clinicaltrials.gov) -  Mar 11, 2022   
    P1,  N=60, Recruiting, 
    Laboratories should have a strategy for alternative analyses in the event that the drugs interfere with assessment of the patient's paraprotein. Trial completion date: Dec 2021 --> Aug 2024 | Trial primary completion date: Dec 2021 --> Jun 2024
  • ||||||||||  Darzalex (daratumumab) / J&J
    Genome-wide CRISPR-cas9 screening identifies KDM6A as a modulator of CD38 expression in multiple myeloma: Therapeutic implications (E-Poster Website) -  Mar 9, 2022 - Abstract #AACR2022AACR_6829;    
    Daratumumab (Dara) is the first-in-class monoclonal antibody targeting CD38 which triggers both direct and immune mediated cytotoxicity in preclinical in vitro and in vivo models of multiple myeloma (MM) in the bone marrow (BM) milieu...Taken together, our studies demonstrate that KDM6A regulates H3K27me3 level on CD38 promotor area and CD38 expression in MM. Moreover, we validate that combination treatment with EZH2 inhibitor and Dara can overcome Dara resistance in preclinical MM models, providing the rationale for combination clinical trials to overcome Dara resistance and improve patient outcome.
  • ||||||||||  talquetamab (JNJ-64407564) / J&J
    A therapeutic antibody against G-protein-coupled receptor class 5 member D to treat multiple myeloma (E-Poster Website) -  Mar 9, 2022 - Abstract #AACR2022AACR_6752;    
    Compared to the GPRC5D antibody in clinical (JNJ-64407564), this antibody has a higher affinity to 293T cells overexpressing GPRC5D (EC50=1.9nM vs. 3nM), MM cell lines, and MM patient samples...At last, MM patient bone marrow samples cultured in vitro with this bispecific antibody increased cell death of the CD138+ population. In summary, the GPRC5D antibody could efficiently target Multiple myeloma tumor cells.
  • ||||||||||  Sarclisa (isatuximab-irfc) / Sanofi, K-NK004 / Sanofi
    CD38KO K-NK cells prevent NK cell fratricide effect and improve isatuximab-mediated cytotoxicity against multiple myeloma cells (Section 37) -  Mar 9, 2022 - Abstract #AACR2022AACR_6085;    
    Indeed, addition of SAR444245 was found to further enhance the cytotoxic activity of CD38KO K-NK cells against LP-1 MM cells when combined with Isatuximab, resulting in an overall superior and sustained cytotoxicity. These data suggest that deletion of CD38 mitigates NK cell fratricide and improves Isatuximab-mediated ADCC against MM cells, and provide evidence for the therapeutic potential of the triple combination CD38KO NK cells, Isatuximab and SAR444245 in the setting of MM.
  • ||||||||||  Combining dual CAR iPSC-derived immune cells with antibody for multi-antigen targeting to overcome clonal resistance in multiple myeloma (Section 36) -  Mar 9, 2022 - Abstract #AACR2022AACR_6069;    
    These combinations were further tested in vivo against a disseminated model of multiple myeloma where BCMA/MICA dual CAR-iNK cells demonstrated superior tumor control relative to single-CAR controls, and TGI was augmented with the addition of Daratumamab. These data highlight the applicability of a multi-targeted approach in MM patients, whereby MM dual-CAR NK and/or T cells maintain responsiveness to malignant cells that shed or downregulate tumor antigens to evade treatment.
  • ||||||||||  Darzalex (daratumumab) / J&J
    Novel multifunctional tetravalent CD38 NKp46 FLEX NKTM engagers actively target and kill multiple myeloma cells (Section 32) -  Mar 9, 2022 - Abstract #AACR2022AACR_5246;    
    In peripheral blood mononuclear cell hemato-toxicity studies depletion of monocytes and NK cells were observed with daratumumab but no depletion was observed with the CD38 NKp46 engager with the mutant Fc. These results suggest that the CD38 NKp46 engagers have a favorable NK cell engager profile for targeting CD38 expressing multiple myeloma that’s distinct from daratumumab.
  • ||||||||||  MT-5111 / Molecular Templates, MT-6402 / Molecular Templates, MT-0169 / Molecular Templates
    Engineered toxin bodies (ETBs) targeting Trop2 (Section 22) -  Mar 9, 2022 - Abstract #AACR2022AACR_2711;    
    AST enabled Trop2 targeted ETBs are capable of delivering viral antigens for multiple HLA types and inducing cytokine secretion and T-cell mediated killing in a co-culture assay of Trop2 target cells with antigen matched HLA type and antigen specific T-cells. These pre-clinical in vitro data suggest AST enabled Trop2 targeted ETBs have the potential to deplete Trop2 positive malignancies through multiple unique mechanisms of action.
  • ||||||||||  Darzalex IV (daratumumab) / J&J, Sarclisa (isatuximab-irfc) / Sanofi
    Clinical, Journal:  An evaluation of isatuximab, pomalidomide and dexamethasone for adult patients with relapsed and refractory multiple myeloma. (Pubmed Central) -  Mar 3, 2022   
    Isatuximab in combination with pomalidomide and dexamethasone offers a new treatment option for those patients with RRMM who are refractory to PIs and lenalidomide, a patient group with poor prognosis and unmet clinical need. The challenge of where it is best placed in the treatment algorithm remains, particularly with the increasing application of daratumumab particularly in the front- and second-line settings.
  • ||||||||||  Blenrep (belantamab mafodotin) / GSK
    Journal:  Belantamab Mafodotin-blmf: A Novel Antibody-Drug Conjugate for Treatment of Patients With Relapsed/Refractory Multiple Myeloma. (Pubmed Central) -  Feb 19, 2022   
    Belantamab mafodotin-blmf (Blenrep) is a first-in-class antibody-drug conjugate directed against B-cell maturation antigen (BCMA) that obtained U.S. Food and Drug Administration accelerated approval in August 2020 for patients with multiply relapsed/refractory MM. This article provides information on the mechanism of action, efficacy, safety, monitoring, and current place in therapy for belantamab mafodotin-blmf.
  • ||||||||||  Darzalex IV (daratumumab) / J&J
    How it started and where is it going - Development of VLA4 and CD38 Targeted Molecular Imaging Agents for Multiple Myeloma (Marriott Grand Ballroom: Section 5 (Marriott Marquis San Diego Marina)) -  Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_7348;    
    The CD38 targeted molecular imaging performed with daratumumab conjugates showed that fluorescent labelling did not affect the biologic activity of the native antibody and allowed for evaluation of the antibody conjugates on a whole-body and cellular level.Conclusions. Our results demonstrate the utility of plasma cell specific tracers for precision imaging and therapy of MM.
  • ||||||||||  Clinical, Review, Journal, HEOR, Real-world evidence:  Real-World Treatment of Patients With Relapsed/Refractory Myeloma. (Pubmed Central) -  Jan 26, 2022   
    Interestingly, RW observations may serve as proof of concept for designing novel clinical trials, as is the case with retreatment studies. In conclusion, clinical trial and RW data are complementary, and they should be considered to improve both clinical trial design and clinical practice.
  • ||||||||||  Clinical, Review, Journal:  The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies. (Pubmed Central) -  Jan 11, 2022   
    This comprehensive review addresses the fundamentals and controversies regarding RRMM, and discusses the main aspects of management and treatment. The basis for the clinical management of RRMM (complexity of clinical scenarios, key factors to consider before choosing an appropriate treatment, or when to treat), the arsenal of new drugs with no cross resistance with previously administered standard first line regimens (main phase 3 clinical trials), the future outlook including the usefulness of abandoned resources, together with the controversies surrounding the clinical management of RRMM patients will be reviewed in detail.