Younger patient with lymphoma subtype live longer with ibrutinib added to therapy

The addition of ibrutinib to R-CHOP chemo-
therapy improved overall survival among
trial participants aged 60 and younger. –
Credit NCI

CANCER DIGEST – Nov. 6, 2021 – In a surprising result, researchers have found that adding ibrutinib (Imbruvica®), a targeted therapy, to chemotherapy can improve survival for young people with a type of the most common form of lymphoma, a new analysis in the Nov. 4, 2021 Cancer Cell shows.

The results stem from the PHOENIX clinical trial testing the combination of standard chemotherapy with the targeted therapy ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma comprising 40 percent of all lymphomas in the world.

Initially the data from that National Cancer Institute study seemed to show that the ibrutinib did not help patients live longer overall. Upon further analysis, however, the researchers examining biopsies from the patients’ tumors found that patients with a specific subtype of the disease known as MCD and N1 had an exceptional response to the treatment combination. All of those patients were surviving without disease three years after diagnosis.

“People thought the trial didn’t work,” Louis M. Staudt, M.D., Ph.D., chief of the Lymphoid Malignancies Branch in the Cancer for Cancer Research at NCI said in a press release. “But there was something interesting going on—if you just considered younger patients under the age of 60, they had a real benefit from ibrutinib, and we now understand why.”

Ibrutinib works by blocking a protein called, Bruton tyrosine kinase, that plays a role in the growth and survival of B cells, a type of white blood cell that makes antibodies. Patients with DLBCL have been successfully treated with a combination therapy known as R-CHOP that uses cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab. However, treatment success varies widely in patients so the researchers wanted to know why.

In a previous trial involving just relapsing patients who had been treated with R-CHOP the investigators found that treating these patients with ibrutinib alone caused tumor shrinkage in 37 percent of patients with one type of DLBCL but only 5 percent of those with a different subtype of the disease.

Based on that result the PHOENIX trial was designed to evaluate the effect of adding ibrutinib to R-CHOP therapy. Disappointingly, the overall results seem to show no effect on the entire patient group of 838 patients that included people over 60 years old.

It was only when they looked at just the younger patients did they find a significant improvement in survival. Further analysis revealed differences in response by genetic subtype of the disease with those with the MCD and N1 subtypes having the greatest improvement in survival.

“For years we have only had chemotherapy and rituximab to offer these patients,” Staudt said. “Now, we hope that adding ibrutinib to current therapy may give younger patients a better chance of surviving this aggressive cancer.”

Source: NCI press release