Tafasitamab for the treatment of relapsed or refractory diffuse large B-cell lymphoma

Abstract

Introduction: Patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) require further treatment options, especially in cases that cannot tolerate stem cell transplant or cytotoxic chemotherapy. CD19 has emerged as an attractive target in B-cell malignancy and is the subject of several therapeutic strategies. The anti-CD19, humanized, monoclonal antibody tafasitamab (MOR208) has an engineered, modified Fc region with increased affinity for Fcγ receptors, leading to increased cytotoxicity via natural killer cells and macrophages (antibody-dependent cellular cytotoxicity and antibody-dependent cell-mediated phagocytosis) in a promising approach. Areas covered: The development of tafasitamab is reviewed, together with the pharmacokinetics and clinical experience of tafasitamab in R/R DLBCL; clinical data have led to FDA approval and inclusion in NCCN treatment guidelines for tafasitamab in combination with lenalidomide in this indication. Expert opinion: Patients with R/R DLBCL who have failed rituximab-containing regimens may be resistant to CD20-directed therapies; therefore, therapies with an alternative mode of action are of great interest in this setting. Tafasitamab, an anti-CD19 monoclonal antibody, in combination with lenalidomide has demonstrated promising efficacy for patients with R/R DLBCL who are ineligible for autologous stem cell transplantation. This could provide an alternative approach to classical chemotherapy-based regimens in the relapsed setting.

Current and emerging monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies in treatment of lymphoma

“…Tafasitamab targets CD19 which is expressed on both immature and mature B cells. Tafasitamab has a modified Fc portion which enhances ADCC and ADP activity of effector cells against NHL tumor cells [ 26 , 27 ].…”

“…Future studies may also focus on combining tafasitamab with chemotherapy in the frontline treatment of DLBCL provided tolerabilty is confirmed in early studies [27] . In general, tafasitamab is well tolerated with the most common adverse events being cytopenias that were more profound when used in combination with lenalidomide [ 26 , 27 ].…”

Monoclonal Antibodies (mAbs) Approved for Cancer Treatment in the 2020s

“…Tafasitamab (also known as Monjuvi ® , tafasitamab-cxix, MOR208, and XmAb5574) is a humanized monoclonal antibody with great targeting ability and specificity towards CD19 developed by MorphoSys AG (26)(27)(28)(29)(30). CD19 is a surface antigen that is expressed from the early developmental stages of pro-B-cells until its downregulation at the final differentiation stage of B cells, in which they develop into antibody-secreting plasma cells (26).…”

Antibody‐Drug‐Conjugate Therapy for Hematological Cancers: Matching Cell Biology with Clinical Benefit

“…The recent FDA approval of Tafasitamab shows that an alternate approach is to focus on using ant-CD19 mAb to improve conscription on cytolytic NK cells. [149] CD19 wash also the target of the first CAR-T cells to receive FDA approval but here too, target biology, such as long-term modulation of expression may be raising hurdles, despite the initial clinical successes. Aside from the potentially hazardous toxicity profile and tremendous financial burden of the treatment process, not all patients respond to CAR-T cells and only a minority of these sustain a durable response, implying the existence of resistance mechanisms to CAR-T cell therapy.…”