Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc
Journal website https://www.thejh.org

Review

Volume 12, Number 4, August 2023, pages 145-160

Harnessing the Immune System: An Effective Way to Manage Diffuse Large B-Cell Lymphoma

Figures

Figure 1.
Figure 1. Immunological targets in DLBCL. DLBCL: diffuse large B-cell lymphoma.
Figure 2.
Figure 2. Effects of immunomodulatory agents.
Figure 3.
Figure 3. Monoclonal antibodies.
Figure 4.
Figure 4. Targeting macrophages with anti-CD47 antibody (magrolimab).
Figure 5.
Figure 5. Antibody-drug conjugate.
Figure 6.
Figure 6. CARs and tumor cell interaction. CARs: chimeric antigen receptor T cells.

Table

Table 1. Immune-Mediated Interventions in the Management of DLBCL
 
Therapeutic agentTargetFunctional characteristicsTherapeutic role in DLBCL
Lenalidomide [3], pomalidomide [4]CereblonLEN/POM increase NK cell function and IL2 production and decrease angiogenesisTafasitamab + 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.)CD19Is present during all phases of B cell development until terminal differentiation is needed for signal transductionTafasitamab 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, CD3Bispecific antibody links CD3 of effector and CD19 of tumor cellsPhase II trial in R/R DLBCL: ORR of 43%
Rituximab [5], ofatumumab [12], obinatuzumab [6]CD20Needed for maturation and activation of B cellsRituximab 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, CD3Bispecific T cell engager Ab.Phase I trials in R/R DLBCL mosunetuzumab: ORR 87%; CR 71%
Inotuzumab ozogamycin [18] (ADC)CD22Needed for B-cell receptor downstream signalingInotuzumab ozogamicin in R/R DLBCL: OS 9.5 months, PFS 3.7 months
Brentuximabvedotin [19] (ADC)CD30“co-stimulatory receptor” for T cells - cytolytic effectIs in phase I/II for R/R DLBCL with R/CHOP: ORR 44%; CR 17%
Polatuzumab vedotin [20] (ADC)CD79bADC-designed to selectively payloadFDA 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.)CD47Cancer cells overexpress CD47 mechanism to evade phagocytosisTTI-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]9p24Increased PDL1 expression from mutant 9p24 locusNivolumab - 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