CD19 antibody-drug conjugate therapy in DLBCL does not preclude subsequent responses to CD19-directed CAR T-cell therapy

Thapa, Bicky; Caimi, Paolo; Ardeshna, Kirit M.; Solh, Melhem; Carlo‐Stella, Carmelo; Kahl, Brad S.; Hamadani, Mehdi

doi:10.1182/bloodadvances.2020002587

Cited by 56 publications

(43 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following CAR T-cell therapy, 6 patients had CR, 5 of whom had ongoing CR at 6 months. Notably, the 4 patients with unknown CD19 expression status following ADC therapy achieved a CR with CAR T-cell therapy [10] .…”

Section: Discussionmentioning

confidence: 99%

Anti-CD19 CAR T-cell therapy remission despite prior anti-CD19 antibody Tafasitamab in relapsed/refractory DLBCL

Tabbara

Gaut

Oliai

et al. 2021

Leukemia Research Reports

View full text Add to dashboard Cite

Highlights Disease progression following anti-CD19 monoclonal antibody Tafasitamab treatment should not preclude subsequent anti-CD19 CART-cell therapy. Previous studies have demonstrated sequential anti-CD19 to be effective. Larger studies among R/R DLBCL patients across anti-CD19 modalities are needed to guide sequencing of therapies following initial anti-CD19 therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-CD19 CAR T-cell therapy remission despite prior anti-CD19 antibody Tafasitamab in relapsed/refractory DLBCL

Tabbara

Gaut

Oliai

et al. 2021

Leukemia Research Reports

View full text Add to dashboard Cite

show abstract

“…Baseline CD19 antigen expression does not appear to influence ORR or risk of subsequent CD19 − relapse. A recent study showed a comparable response to CD19 CAR T therapy in patients who had progressed on previous CD19‐ADC 67 . Majzner et al .…”

Section: Lymphomamentioning

confidence: 96%

The evolving role of allogeneic haematopoietic cell transplantation in the era of chimaeric antigen receptor T‐cell therapy

et al. 2021

View full text Add to dashboard Cite

Summary Chimaeric antigen receptor T‐cell (CAR T) therapy has revolutionized the management of many haematological malignancies. It is associated with impressive disease responses in relapsed or refractory high‐grade B‐cell non‐Hodgkin lymphoma (B‐NHL) and acute lymphoblastic leukaemia (B‐ALL) with durable remissions in a subset of patients. Historically, haematopoietic cell transplantation (HCT) has been the standard consolidation strategy for many of these patients who are now being treated with CAR T. Relapses are frequent after CD19 CAR T therapy in B‐ALL and consolidation with allogeneic HCT (allo‐HCT) may improve survival of patients with high‐risk disease. There appears to be a clear difference in B‐ALL outcomes between paediatric and adult patients, with the latter having a much higher risk of relapse after CAR T therapy. Late relapses are infrequent in patients with B‐NHL and consolidation with allo‐HCT may not be needed in patients who achieve a complete remission after CAR T therapy. Future registry‐based and prospective studies will hopefully provide the needed data in the future to risk‐stratify the recipients of CAR T therapy. Meanwhile, we provide guidance on patient selection and practical issues with performing allo‐HCT after CAR T therapy.

show abstract

“…53 Data for other CD19-targeted therapies have been more promising: in a study of 14 patients with DLBCL who received loncastuximab tesirine, CD19 positivity by immunohistochemistry was not affected by treatment, with CD19directed CAR-T therapy possible after a median 120 days from antibody-drug conjugate failure. 14 Extensive loss of CD19 expression has not been associated with tafasitamab in CLL cells. 18 Limited clinical data support the maintenance of CD19 expression following tafasitamab treatment, with one report of a CR to CAR-T therapy after participation in the L-MIND study.…”

Section: Open Questions For Cd19-directed Therapy In Dlbcl: Treatment Sequencing and Compatibility With Car-tmentioning

confidence: 98%

“…10 Several different approaches have been developed to exploit CD19 on B-cells in patients with R/R DLBCL over the past 5 years, including chimeric antigen receptor T-cell therapy (CAR-T), bispecific antibodies which localize T-cells to CD19, antibody-drug conjugates which deliver a cytotoxic payload to CD19-bearing cells and now tafasitamab in combination with lenalidomide. [11][12][13][14][15] Tafasitamab development, structure, mechanism of action (MOA) and early clinical data Initial attempts to exploit CD19 via murine antihuman CD19 monoclonal antibodies (mAbs), with or without linked toxins, were met with limited success, partly as a result of CD19 internalization following antibody binding and the development of human anti-murine antibodies during treatment. 10,16 The second generation of CD19-targeting antibodies utilized computational algorithms and high-throughput screening to design and select antibodies with specific engineered Fc variant regions to enhance immune effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The use of tafasitamab in diffuse large B-cell lymphoma

Düll

Topp²,

Salles

2021

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

Patients who relapse or are refractory after first-line therapy for diffuse large B-cell lymphoma (DLBCL) frequently have poor prognoses, especially when they are not candidates for autologous stem cell transplant (ASCT). Tafasitamab is a humanized monoclonal anti-CD19 antibody that has recently been approved by the FDA in combination with lenalidomide for the treatment of relapsed/refractory (R/R) DLBCL in patients who are not eligible for ASCT. Tafasitamab has an Fc region which has been modified to have an increased affinity for Fcγ receptors, to potentiate antibody-dependent cellular cytotoxicity and antibody-dependent cell-mediated phagocytosis. Here, we review the development, mode of action and clinical data for tafasitamab in combination with lenalidomide in R/R DLBCL, and discuss the various ways in which this novel antibody could be utilized in the treatment sequence to improve clinical outcomes for patients with DLBCL.

show abstract

CD19 antibody-drug conjugate therapy in DLBCL does not preclude subsequent responses to CD19-directed CAR T-cell therapy

Cited by 56 publications

References 10 publications

Anti-CD19 CAR T-cell therapy remission despite prior anti-CD19 antibody Tafasitamab in relapsed/refractory DLBCL

Anti-CD19 CAR T-cell therapy remission despite prior anti-CD19 antibody Tafasitamab in relapsed/refractory DLBCL

The evolving role of allogeneic haematopoietic cell transplantation in the era of chimaeric antigen receptor T‐cell therapy

The use of tafasitamab in diffuse large B-cell lymphoma

Contact Info

Product

Resources

About