Triple Therapy Combo Effective in Treating DLBCL Subtype, Data Suggest

People with the non-germinal center subtype of diffuse large B-cell lymphoma (non-GCB DLBCL) respond well to initial treatment with Rituxan (rituximab), Imbruvica (ibrutinib), and Revlimid (lenalidomide) — so well that chemotherapy, the standard of treatment, might not be necessary in some cases.

Results from the Smart Start Phase 2 clinical trial (NCT02636322) were recently shared at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago.

The presentation was titled, “Smart start: Final results of rituximab, lenalidomide, and ibrutinib lead in prior to combination with chemotherapy for patients with newly diagnosed diffuse large B-cell lymphoma.”

The non-GCB subtype accounts for 30-40% of DLBCL cases, and is known to be less responsive to chemotherapies than other subtypes of DLBCL, creating a need for other treatments.

The three treatments used in this trial are all aimed at inhibiting the growth of and/or killing immune cells, particularly B cells. Imbruvica is a small molecule that inhibits a protein B cells need to grow; Revlimid is another small molecule that interferes with immune cell growth by mechanisms that still aren’t clear; Rituxan is a monoclonal antibody that targets B cells so that other immune cells can kill them.

The investigator-initiated, single-arm, open-label Smart Start study included 60 adults (median age 64) who had been newly diagnosed with non-GCB DLBCL. They received treatment in eight 21-day cycles. The triple combo was given alone in the first two cycles; the remaining six cycles included these treatments in addition to standard-of-care chemotherapy.

The overall response rate — the number of patients achieving at least a 30% reduction in tumor burden, or complete tumor disappearance — after the first two cycles was measured as a primary outcome assessment.

Among the 52 patients evaluable for efficacy at the end of cycle 2, 44 (84.6%) achieved a response to treatment, including 20 (38.5%) with a complete response.

“The responses we’ve seen have been remarkable. More than 80 percent of our patients have responded and around 40 percent have had a complete response, showing no evidence of cancer, prior to receiving any chemotherapy,” Jason Westin, MD, a professor at The University of Texas MD Anderson Cancer Center and one of the researchers who ran the trial, said in a press release.

“All patients have gone on to receive standard chemotherapy in combination with these targeted treatments per the protocol, and, so far, we’ve had a 100 percent response rate,” he said.

Side effects were reported to be generally mild, with most of those reported being attributed to the chemotherapy, not the targeted treatment.

One patient in the trial died of a fungal infection, attributed to high doses of corticosteroids in addition to the treatment. Because of this, corticosteroids are not allowed for subsequent patients undergoing the treatment; there haven’t been any more of these infections.

Additional studies with more patients will be needed to confirm these results, but the initial data suggest that this type of targeted therapy could bolster — or in some cases render obsolete — the traditional chemotherapy that has been the mainstay of treatment for decades.

“Standard treatment for large-cell lymphoma has been largely stagnant for the better part of 40 years, despite many advances in our understanding of the disease and a host of new medications,” Westin said. “It’s exciting to see an idea that worked in the lab now beginning to yield results and show this is a potentially new way forward to fight this disease.”