Epratucyn (epratuzumab)

The introduction of rituximab has improved the outcomes in CD20 positive cases. Other monoclonal antibodies, such as tafasitamab (anti-CD19), obinutuzumab (anti-CD20) and epratuzumab (anti-CD22) have been tested in trials (NCT05366218, NCT04920968, NCT00098839)...In contrast to ATP site inhibitors such as dasatinib and ponatinib, the novel first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor asciminib did not significantly impact ADCC in our settings. Our results suggest that asciminib should be considered in clinical trials.

P3, N=700, Completed, Charite University, Berlin, Germany | Active, not recruiting --> Completed

During consolidation, patients were randomized to receive the CD22-directed monoclonal antibody epratuzumab in addition to backbone chemotherapy... Both arm A and B were effective in this large multi-national trial. EFS and OS probabilities compare favorably to results recently published by other cooperative groups. In particular, the outcome of patients with early IEM relapse or with late BM relapse and MRD poor response is encouraging confirming the benefit of allo HSCT in these subgroups.

Other than that, a resistance mechanism to rituximab emerged by inducing a failure in the apoptosis mechanism...Here came the development of 90Y-ibritumomab tiuxetan and 131I-tositumomab. After it, humanized anti-CD20 emerged ofatumumab, IMMU106 (veltuzumab) in 2005, and ocrelizumab which are considered as second generation anti-CD20 and 3 generation anti-CD20 include AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutuzumab). Also multiple other agents emerged targeting different surface cell antigens like CD52 (alemtuzumab), CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab], Brentuximab vedotin), CD40 (SGN-40), and CD79b (Polatuzumab). Other agents include MAB targeting T-Cells like mogamulizumab, Denileukin Diftitox and BiTEs or bispecific T cell engagers like Mosunetuzumab, Glofitamab, and Epcoritamab...Another important aspect in immunotherapy is the half-lives of the medication which is an important factor that can influence the evaluation of the response. The MAB treatment showed important benefit in the treatment of iNHL and it continuously shows how rapidly it can develop to provide optimum care and benefit to patients with iNHL.

A variety of therapies targeting CD22 have been developed, including monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, chimeric antigen receptor T cells, and bispecific antibodies. Here, we review the biology of CD22 and key therapies targeting CD22 in lymphoid malignancies.

ADCT-602 is an antibody drug conjugate (ADC) composed of Emab-C220, an engineered version of the anti-CD22 humanized IgG1 antibody epratuzumab, site-specifically conjugated to SG3249, which includes the DNA minor groove crosslinking pyrrolobenzodiazepine (PBD) dimer SG3199 linked to the antibody via a protease-cleavable linker (Zammarchi et al, ASH 2016). Expression signatures and other features (MZL or DHT DLBCL histology), but not the expression levels of its target, were associated with different sensitivity to the ADC. Our data supports the clinical evaluation of ADCT-602 in patients with B-cell lymphoma in addition to B-ALL.

The most common immediately prior line of therapy included bendamustine and rituximab (BR, n=16); rituximab, cyclophosphamide, adriamycin, vincristine, prednisone (RCHOP, n=6); double-monoclonal antibody containing regimens(rituximab-galiximab; rituximab-epratuzumab (n=3)), radioimmunotherapy (n=3), and allogeneic bone marrow transplant (n=2). Additional follow-up is underway to determine if positive pts will eventually relapse. CONCLUSIONS These data are the first to demonstrate that a high proportion of FL pts in a prolonged clinical remission have undetectable DNA by sensitive next generation sequencing, without evidence of clinical progression, and are potentially cured of their disease.

In the more intensive re-induction British protocol (ALL-R3), Mitoxantrone and Idarubicin were compared, and it was observed that Mitoxantrone resulted in significant increases in both overall survival and progression-free survival rates due to the reduction of the relapse rate...Although the response rate was 44% in the phase 2 Clofarabine + Cyclophosphamide study performed in the previously intensively treated group, there was no benefit in the COG study containing Clofarabine + high dose Cytarabin (Ara-C) in the second or more recurrent ALL cases...The COG group demonstrated that the addition of Nelarabine to high-risk T-ALL treatment based on the BFM treatment scheme had an acceptable toxicity (mostly peripheral neuropathy) and observed an uneventful survival rate higher in the Nelarabine group...For example, liposomal vincristine has received FDA approval for the treatment of adult ALL. Some of the PEG binding molecules are already in use in daily practice (PEG-Asparaginase), while some have already been used in studies (PEGdoxorubicin)...Response rates increased to 73% with the addition of Bortezomib in children with precursor B (pB) cell ALL who had previously received intensive chemotherapy...The efficacy of Carfilzomib, a second generation proteosome inhibitor, is under investigation in phase 1-2 studies...In a phase 2 study in adult subjects, the combination of Decitabine and Vorinostat showed an acceptable toxicity and promising response rates, but the combination of these two drugs in a UK-ALL03-type re-induction in pediatric cases led to an unacceptable toxicity...Ruxolitinib studies are continuing in CRLF2, JAK/EPOR and JAK-STAT/MAPK subgroups and Dasatinib in ABL-class subgroup...mTOR inhibitors (Rapamycin, Evarolimus and Temsirolimus) are often used in combination with re-induction protocols for this pathway inhibition...The MEK inhibitor Selumetinib in this pathway has yielded active results in treatment in preclinical studies. The second-generation Flt3 inhibitor Quizartinib is being studied in patients with ALL. Since bcl-2 pathway prevents apoptosis, the efficacy of bcl-2 inhibitors, Navitoclax and Venetoclax, in ALL is being investigated...Palbociclib, CDK6 inhibitor, is used as monotherapy in KMT2A-r acute leukemia...Immunotherapy Antibody-based immunotherapy Blinatumomab: It is an antibody capable of binding to CD19 and CD3 and transmitting T-cell cytotoxicity to lymphoblasts presenting CD19...Denintuzumab mafodatin: It is a humanized CD19 antibody bound with monomethyl auristatin F (MMAF)...ADCT-402: It is a humanized anti-CD19 antibody conjugated with Pyrrolobenzodiazepine dimer cytotoxin...DT2219: It is a bispecific, recombinant, diphtheria toxin-based immunotoxin that recognizes CD19 and CD22-presenting cells...Inotuzumab ozogamicin: It is a novel monoclonal antibody against CD22 conjugated to the toxin Calicheamicin...Epratuzumab: It is a humanized monoclonal anti-CD22 antibody...Rituximab: It is a chimeric monoclonal CD20 antibody...Ofatumumab: It is a humanized anti-CD20 antibody...Obinutuzumab: It a type II humanized anti-CD20 monoclonal antibody...Etanercept (anti-TNF) and Tociluzumab (anti IL-6) can be used in the treatment of cytokine release syndrome. There are many marching studies on CAR-T cell therapy.