| Lenalidomide [3], pomalidomide [4] |
Cereblon |
LEN/POM increase NK cell function and IL2 production and decrease angiogenesis |
Tafasitamab + lenalidomide in NGC DLBCL - CR 43%, PR 18%; pomalidomide and pembrolizumab in DLBCL - RR 50%, OS 14.7 months |
| Axicabtagene ciloleucel [4], tisagenlecleucel [7], lisocabtagene maraleucel [8] CAR therapy loncatuximab tesirine (ADC) [9], tafasitamab [10] (monoclonal Ab.) |
CD19 |
Is present during all phases of B cell development until terminal differentiation is needed for signal transduction |
Tafasitamab in combination with lenalidomide is approved for treatment of R/R DLBCL patients ineligible for ASCT. Loncastuximab tesirine is approved as a third line treatment in patients with R/R DLBCL - ORR 45.6%, CR 26.7%. Axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel - axi-cel 4-year OS 43%; tisa-cel 1-year OS 55.1%; liso-cel 57.9% - there is no evidence suggestive of difference in survival between these agents. |
| Blinatumumab (BiTE) [11] |
CD19, CD3 |
Bispecific antibody links CD3 of effector and CD19 of tumor cells |
Phase II trial in R/R DLBCL: ORR of 43% |
| Rituximab [5], ofatumumab [12], obinatuzumab [6] |
CD20 |
Needed for maturation and activation of B cells |
Rituximab is approved for treatment of R/R DLBCL in various settings. Ofatumumab and obinutuzumab (ORR 37%) are not FDA approved. |
| Mosenutuzumab [13], glofitamab [14], plomatamab [15], epcoritamab [16], odonextamab [17] (BiTE) |
CD20, CD3 |
Bispecific T cell engager Ab. |
Phase I trials in R/R DLBCL mosunetuzumab: ORR 87%; CR 71% |
| Inotuzumab ozogamycin [18] (ADC) |
CD22 |
Needed for B-cell receptor downstream signaling |
Inotuzumab ozogamicin in R/R DLBCL: OS 9.5 months, PFS 3.7 months |
| Brentuximabvedotin [19] (ADC) |
CD30 |
“co-stimulatory receptor” for T cells - cytolytic effect |
Is in phase I/II for R/R DLBCL with R/CHOP: ORR 44%; CR 17% |
| Polatuzumab vedotin [20] (ADC) |
CD79b |
ADC-designed to selectively payload |
FDA approved. Based on phase II trial (in combination deliver an ultra-toxic rituximab/bendamustine in R/R DLBCL: ORR 41.5%; CR 38.7% |
| Magrolimab [21] (monoclonal Ab.) |
CD47 |
Cancer cells overexpress CD47 mechanism to evade phagocytosis |
TTI-622-01 (NCT03530683) is a multi-center phase 1a/1b study ongoing with R/R DLBCL. Phase 2 study: ORR 40%; CR 33% |
| Check point inhibitors [22-25] |
9p24 |
Increased PDL1 expression from mutant 9p24 locus |
Nivolumab - phase II study in R/R DLBCL not eligible for ABMT (ORR 10%). Pembrolizumab in phase III trial in untreated DLBCL with R-CHOP (ORR 25%). Pembrolizumab in phase Ib in R/R primary med. B cell lymphoma |
