AbbVie, a global biopharmaceutical company, announced encouraging efficacy and safety findings from two separate studies evaluating ibrutinib (Imbruvica) as a combination therapy in two of the most common types of non-Hodgkin's lymphoma (NHL): diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Imbruvica, a first-in-class Bruton's tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

In a phase 1b study of patients with relapsed/refractory (R/R) DLBCL, the investigational combination of ibrutinib, rituximab, and escalating doses of lenalidomide were tested. Preliminary efficacy results demonstrated the highest response rate was observed in patients with the worst prognosis subtype (non-GCB) and in patients with transformed disease. These data will be presented in an oral presentation at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA.

"Though standard therapy can cure over half of patients with diffuse large B-cell lymphoma (the most common form of aggressive lymphoma), patients with relapsed or refractory disease do overall poorly with only less than a quarter of patients efficiently salvaged with current strategies including stem cell transplantation," said Andre Goy, M.D., chairman and executive director at John Theurer Cancer Center at Hackensack University Medical Center in New Jersey and lead investigator of the study. "We are encouraged by these results in a heavily pretreated and refractory population and look forward to further evaluating the efficacy of ibrutinib combination therapy with rituximab and lenalidomide in the phase 2 portion of the study."

Separately at the meeting, data from a phase 2 multicenter study showed that the combination of ibrutinib and rituximab produced favorable response rates in patients with previously untreated FL. At a median time on study of 22 months, the overall response rate (ORR) was 85%, with 35% of patients achieving a complete response (CR).2 The data were presented in a poster presentation on December 3.

"We are highly encouraged by this longer-term data showing strong and durable responses that appear to improve with an extended treatment duration," said Nathan Fowler, M.D., Associate Professor, Department of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX and lead investigator of the study. "The results of the study to date suggest that the addition of ibrutinib to rituximab in the front-line follicular lymphoma setting provides enhanced outcomes over rituximab alone."

DLCBL is an aggressive B-cell lymphoma and the most common subtype of non-Hodgkin's lymphoma. Despite 50-60% of patients being cured with standard chemo-immunotherapy, patients who relapse have poor outcomes. FL is the most common subtype of indolent non-Hodgkin's lymphoma. It is often slow-growing, but is considered incurable in advanced stages. Over time, about one-third of FL cases advance to the fast-growing DLBCL.

"The response rates observed with ibrutinib combination therapy in treatment-naïve follicular lymphoma and relapsed/refractory diffuse large B-cell lymphoma show promise for patients with two different types of non-Hodgkin's lymphoma," said Darrin Beaupre, M.D., Ph.D., Head of Early Development and Immunotherapy at Pharmacyclics LLC, an AbbVie company. "We pioneered the development of BTK inhibition with ibrutinib, and we continue to progress our robust development program. Based on the encouraging phase 2 study results in FL, we are initiating a phase 3 study of the combination of ibrutinib and rituximab in the first-line setting."

Subjects with R/R DLBCL were treated with the investigational combination of ibrutinib 560 mg once daily, rituximab 375 mg/m2 on day one for six cycles and escalating doses of lenalidomide. Preliminary data for 45 patients showed responses on 15 mg, 20 mg, and 25 mg lenalidomide, with responses for patients with the non-GCB subtype (response-evaluable population) seen in more than half of the subjects. Patients with transformed disease also showed favorable responses. Overall, the treatment combination was tolerable. The most frequent Grade 3 or 4 adverse events (AEs) were neutropenia (38%), thrombocytopenia (11%), and maculopapular rash (11%). Based on safety data from this portion of the study, the phase 2 portion of the trial is being initiated.

Imbruvica is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton's tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells. Imbruvica blocks signals that tell malignant B cells to multiply and spread uncontrollably.

Imbruvica is approved to treat patients with CLL/SLL including patients with 17p deletion, patients with mantle cell lymphoma who have received at least one prior therapy and patients with Waldenström's macroglobulinemia. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

Imbruvica was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy designation pathway.

Imbruvica is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. Imbruvica has one of the most robust clinical oncology development programs for a single molecule in the industry with nearly 30 (n=27) company-sponsored trials underway, 14 of which are phase 3. In addition, there are more than 40 (n=44) investigator-sponsored trials taking place around the world. To date, more than 65,000 patients around the world have been treated with Imbruvica in clinical practice and clinical trials.