Dr. Witzig on Emerging Agents in Diffuse Large B-Cell Lymphoma

Thomas E. Witzig, MD
Published: Tuesday, Nov 08, 2016



Thomas E. Witzig, MD, hematologist-oncologist, Mayo Clinic, discusses some of the emerging agents being utilized in the treatment of patients with diffuse large B-cell lymphoma (DLBCL).

According to Witzig, patients with DLBCL have generally been recommended treatment with 6 cycles of R-CHOP. However, over the last decade or so, research has identified several different pathways in this disease, with 4 different drugs to target those pathways.

One drug, lenalidomide (Revlimid) is an immunomodulatory agent with activity in lymphoid malignancies occurring primarily through immune modulation and anti-proliferative effects. This agent has shown promise when combined with standard R-CHOP, says Witzig, and it is currently being investigated in a randomized international trial.

Ibrutinib (Imbruvica), a BTK inhibitor, has also been tested in phase I, II, and III trials. In a phase I/II clinical trial that involved 80 subjects with relapsed/refractory DLBCL, 37% of patients treated with ibrutinib achieved complete or partial responses.

Bortezomib (Velcade), a proteasome inhibitor, is another emerging targeted therapy in this setting. However, says Witzig, trials testing this drug have been negative thus far.

Everolimus (Afinitor), an mTOR pathway inhibitor, has been demonstrated to induce cell cycle arrest in preclinical studies in DLBCL. Moreover, it is synergistic with rituximab (Rituxan), and the combination of these 2 agents has shown encouraging results without increasing toxicity.


Thomas E. Witzig, MD, hematologist-oncologist, Mayo Clinic, discusses some of the emerging agents being utilized in the treatment of patients with diffuse large B-cell lymphoma (DLBCL).

According to Witzig, patients with DLBCL have generally been recommended treatment with 6 cycles of R-CHOP. However, over the last decade or so, research has identified several different pathways in this disease, with 4 different drugs to target those pathways.

One drug, lenalidomide (Revlimid) is an immunomodulatory agent with activity in lymphoid malignancies occurring primarily through immune modulation and anti-proliferative effects. This agent has shown promise when combined with standard R-CHOP, says Witzig, and it is currently being investigated in a randomized international trial.

Ibrutinib (Imbruvica), a BTK inhibitor, has also been tested in phase I, II, and III trials. In a phase I/II clinical trial that involved 80 subjects with relapsed/refractory DLBCL, 37% of patients treated with ibrutinib achieved complete or partial responses.

Bortezomib (Velcade), a proteasome inhibitor, is another emerging targeted therapy in this setting. However, says Witzig, trials testing this drug have been negative thus far.

Everolimus (Afinitor), an mTOR pathway inhibitor, has been demonstrated to induce cell cycle arrest in preclinical studies in DLBCL. Moreover, it is synergistic with rituximab (Rituxan), and the combination of these 2 agents has shown encouraging results without increasing toxicity.

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