New Directions in Relapsed/Refractory Diffuse Large B-cell Lymphoma

Kieron Dunleavy, MD

Even though diffuse large B-cell lymphoma (DLBCL) is often viewed as a single type of non-Hodgkin lymphoma, research has shown that the disease is actually heterogeneous, suggesting that patients with varying subtypes should receive different courses of treatment.

Kieron Dunleavy, MD, a staff clinician with the National Cancer Institute, presented the available research on these DLBCL subtypes at the 16th Annual International Congress on Hematologic Malignancies.

Dunleavy said that there are 3 key subtypes: germinal center B-cell like DLBCL (GCB), activated B-cell DLBCL (ABC), and primary mediastinal B-cell lymphoma (PMBL).

Knowing these subtypes can help researchers determine appropriate targets for both distinguishing among subtypes and treating the disease. For example, the B-cell lymphoma 6 (BCL6) protein is associated with follicular lymphoma, but research has shown a close association between the protein and GCB.

“BCL6 almost always appears in GCB DLBCL,” Dunleavy said.

Another protein, c-MYC, is closely associated with GCB. Dunleavy said that patients with lymphoma treated with R-CHOP (rituximab [Rituxan], cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) had a much worse prognosis if they were c-MYC—positive.

Based on early clinical trials, there is at least 1 therapeutic agent that appears to have had positive results on the ABC subtype. In a study (View Abstract) presented at the 2011 American Society of Hematology Annual Meeting, the Bruton’s tyrosine kinase inhibitor PCI-32765 was tested in 8 patients with relapsed or refractory ABC DLBCL. The results showed that 2 patients achieved complete response for 11+ and 5 months, respectively; 3 patients achieved stable disease for 4, 2, and 2 months, respectively; and 3 patients had progressive disease. The drug was generally well tolerated across the patient population.

“We've seen a wide range of activity with this drug,” Dunleavy said. “It’s certainly a promising agent.”

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