Table 1.
Targeted cell surface molecules in treatment of NHL.
| Cell surface targets | Biological function | Targeted therapies | FDA approval status and indications in R/R DLBCL |
|---|---|---|---|
| CD19 | Co-receptor for the B-cell antigen receptor complex (BCR). It decreases the threshold for activation of downstream signaling pathways. | Tafasitamab (Mab) Loncastuximab tesirine, Coltuximab ravtansine (ADC) Axicabtagene ciloleucel, Tisagenlecleucel, Lisocabtagene maraleucel (CAR) |
Tafasitamab in combination with lenalidomide is approved for treatment of R/R DLBCL patients ineligible for ASCT. Approval was based on the phase 2 L-MIND trial (NCT02399085) Loncastuximab tesirine is approved as a third line treatment in patients with R/R DLBCL based on the phase 2 trial (NCT03589469). Axicabtagene ciloleucel, Tisagenlecleucel, Lisocabtagene maraleucel (CAR) are FDA approved for the treatment of R/R DLBCL after two prior lines of therapy Coltuximab ravtansine is not approved. It was tested in a phase 2 trial in patients with R/R DLBCL |
| CD20 | It promotes development, differentiation, and activation of B-lymphocytes. | Rituximab, Obinutuzumab, Ofatumumab (MAb) Ibritumomab tiuxetan, Iodine-131 tositumomab (radiolabeled mab) MT3724 (Engineered toxin body) |
Rituximab approved for treatment of R/R DLBCL in various settings. Iodine 131-tositumomab is approved for treatment of R/R transformed follicular lymphoma. MT3724 was tested in phase 1 trial. Phase 2 study is ongoing (NCT02361346) |
| CD19 X CD3 | Blinatumumab (BiTE) | Not FDA approved. Blinatumomab was tested in phase 2 trials in R/R DLBCL (NCT01741792). Most phase 3 trials in R/R DLBCL were held due to modest activity and presence of more promising immunotherapeutic agents | |
| CD20 X CD3 | Mosenutuzumab, Glofitamab, Plomatamab, Epcoritamab, Odonextamab(BiTE) | -Not FDA approved -BiTEs were tested in phase 1 trials in R/R DLBCL with promising results (NCT03075696) (NCT02500407) (NCT03671018) (NCT03625037) (NCT02290951) (NCT02924402) -Phase 2 trials are ongoing. -Phase 3 trials are ongoing (NCT04628494) (NCT04408638) (NCT05171647) |
|
| CD22 | It mediates B-cell interactions and localization in lymphoid tissues. It regulates BCR signaling. |
Epratuzumab (mAb) Pinatuzumab vedotin, Inotuzumab ozogamycin (ADC) |
-Not FDA approved -Epratuzumab has been tested in a phase 2 trial including patients with R/R DLBCL. Pinatuzumab vedotin (NCT01691898) and inotuzumab ozogamycin (NCT00867087) have been tested in phase 2 trials. Phase 3 trial of inotuzumab was discontinued. |
| CD30 | It activates NF-κB transcription | Brentuximab vedotin (ADC) | -Not FDA approved for R/R DLBCL but used occasionally off label when CD30 is expressed and especially in patients unfit for chemotherapy. -Brentuximab + lenalidomide + rituximab regimen is being compared against placebo + rituximab + lenalidomide in a phase 3 trial (ECHELON-3) of R/R DLBCL patients |
| CD79b | Along with CD79a, it initiates the signal transduction cascade activated by BCR which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. | polatuzumab vedotin (ADC) | Polatuzumab vedotin was approved in combination with bendamustine + rituximab for treatment of R/R DLBCL patients who are ineligible for ASCT and after two lines of therapy. Approval came based on initial results of the phase 2 trial (NCT02257567) |
| CD47 | Macrophage checkpoint that provides “do not eat me signal” | magrolimab (mab) | Not FDA approved. Studied in a phase 1 and 2 (NCT02953509) in patients with R/R DLBCL. Phase 2 studies (NCT03309878) are ongoing |