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Novel Therapies for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

ABSTRACT: The most common type of non-Hodgkin lymphoma in adults is diffuse large B-cell (DLBCL). There is a historical unmet need for more effective therapies in the 2nd and 3rd line setting. Emerging immunochemotherapies have shown activity in small studies of heavily pre-treated patients with prolonged remissions achieved in some patients. Anti-CD19 CAR (chimeric antigen receptor) T cells are potentially curative in the 3rd line and beyond setting and are under investigation in earlier lines of therapy. Antibody-drug conjugates (ADC's) such as polatuzumab vedotin targeting the pan-B-cell marker CD79b has proven effectiveness in multiply-relapsed DLBCL patients. Tafasitamab (MOR208) is an anti-CD19 monoclonal antibody producing prolonged remissions when combined with Lenalidomide (LEN) in patients who were not candidates for salvage chemotherapy or autologous stem cell transplant. Selinexor, an oral, small-molecule selective inhibitor of XPO1-mediated nuclear export (SINE), demonstrated prolonged activity against heavily-pretreated DLBCL without cumulative toxicity and is being investigated as part of an oral, chemotherapy-free regimen for relapsed aggressive lymphoma. This article reviews current strategies and novel therapies for relapsed/refractory DLBCL.

SUBMITTER: Harris LJ

PROVIDER: S-EPMC7698117 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Look at the Approved and Emerging Therapies.

Project description:Approximately 40% of patients with diffuse large B cell lymphoma (DLBCL) do not respond or develop relapsed disease after first-line chemoimmunotherapy. A minority of these patients can be cured with autologous hematopoietic stem cell transplantation (AHCT). Although chimeric antigen receptor (CAR) T cells have transformed the treatment paradigm of relapsed/refractory DLBCL, only 30-40% of patients achieve durable remissions. In addition, many patients with relapsed/refractory DLBCL are ineligible to receive treatment with CAR T cells due to comorbidities or logistical limitations. Since 2019, the following four non-CAR T-cell treatments have been approved in relapsed/refractory DLBCL: polatuzumab in combination with bendamustine and rituximab, selinexor, tafasitamab plus lenalidomide, and loncastuximab. In this article, I review the data behind these four approvals and discuss important considerations on their use in clinical practice. I also review emerging therapies that have shown promising early results in relapsed/refractory DLBCL including the bispecific antibodies, antibody-drug conjugates, Bruton tyrosine kinase inhibitors, BCL2 inhibitors, immune checkpoint inhibitors, and epigenetic modifiers.

| S-EPMC8708171 | biostudies-literature

Novel biologic therapies in relapsed or refractory diffuse large B cell lymphoma: CAR-T is not the only answer.

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| S-EPMC8728095 | biostudies-literature

Real World Outcomes in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma Receiving Palliative Intent Therapies.

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Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

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Developing New Strategies for Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

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Mutational Profile and Clonal Evolution of Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

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Decitabine combined with RDHAP regimen in relapsed/refractory diffuse large B cell lymphoma.

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