Category: Clinical Trials

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma, rising in incidence among older populations. The standard of care for the approximate one-third of DLBCL patients who do not achieve remission with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) is salvage high-dose chemotherapy followed by consolidative autologous stem cell transplant, which leads to long-term disease-free survival for only 10-20 percent of relapsed/refractory patients. Patients who relapse within a year of initial therapy, those who relapse after transplant, and those who are ineligible for transplant due to age or comorbidities face the most significant unmet treatment need.

With an eye toward improving therapeutic options and outcomes for this patient population, the Lymphoma Program team, led by Dr. Jia Ruan, collaborated with colleagues nationwide and contributed significantly to a study examining the maximum tolerated dose and preliminary safety and activity of a novel three-drug combination – ibrutinib plus lenalidomide and rituximab – in treatment of relapsed/refractory DLBCL. The team’s encouraging findings were published in the American Society of Hematology’s Blood journal.

The study population consisted of 45 transplant-ineligible DLBCL patients whose disease returned after at least one prior therapy. Patients received oral ibrutinib daily, intravenous rituximab on every first day of six 28-day cycles, and oral lenalidomide on the first 21 days of each cycle. The treatment was provided as continuous chronic therapy in an outpatient clinic setting for as long as patients could derive benefit.

Forty-four percent of patients responded to the triplet, and 28 percent achieved a complete response. The combination performed particularly well (ORR: 65%, CR: 41%) in patients with non-germinal center b cell (non-GCB) DLBCL, a molecular subtype based on disease cell of origin that is not typically associated with favorable prognosis. Common treatment side effects included gastrointestinal complications, fatigue, myelosuppression (reduced blood cell production), hypokalemia (low blood potassium), peripheral edema and skin rash. Side effects could be monitored and mitigated by dose adjustment in the outpatient setting.

“This novel treatment consists of two oral agents typically used to treat B-cell lymphoma, plus the anti-CD20 antibody rituximab, and can be easily administered in the clinic or patient’s home,” said Dr. Jia Ruan. “This effective low-intensity approach makes it very appealing to a broad range of R/R DLBCL patients in need of treatment.”