IMBRUVICA-rituximab combination well tolerated in patients with relapsed or refractory MCL

New IMBRUVICA^® (ibrutinib) Phase II data announced by Pharmacyclics, Inc. (NASDAQ: PCYC) today demonstrates its potential utility as a combination therapy when used with rituximab. Data suggest that the overall efficacy and safety profile of IMBRUVICA is well tolerated when combined with rituximab in patients with relapsed or refractory mantle cell lymphoma (MCL).

IMBRUVICA combination therapy resulted in an 88% overall response rate (ORR) in MCL patients with a complete response rate (CR) of 40%. These results were presented here at the 56th American Society of Hematology (ASH) Annual Meeting. IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

"The positive outcomes seen with IMBRUVICA in combination with rituximab reinforce our decision to pursue its full potential as a single-agent and in combination with other therapies, and underscores the potential IMBRUVICA may offer to patients living with hematologic malignancies," said Danelle James, M.D., M.S., Vice President, Clinical Development, Pharmacyclics. "We are committed to continuing to investigate IMBRUVICA to find the most appropriate options for patients."

Abstract 627: Ibrutinib and Rituximab are an Efficacious and Safe Combination in Relapsed Mantle Cell Lymphoma: Preliminary Results from a Phase II Clinical Trial

IMBRUVICA was combined with rituximab in a single-center, Phase II trial in 50 relapsed/refractory MCL patients. After a median follow-up of 11 months (range 4-16 months). In 34 evaluable patients with lower levels (< 50) of the Ki-67 protein, a known marker associated with cell growth, the ORR was 100% (56% CRs and 44% partial responses [PRs]). In 12 evaluable patients with higher Ki-67 (> 50%) protein levels, the ORR was 50% (8% CRs, 42% PRs).

"IMBRUVICA combination findings demonstrated the potential impact the therapy may have beyond its current use as a single agent, and it may be an important option for certain patients who previously have been more difficult to treat," said Michael Wang, M.D., from the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, Houston, TX, who discussed these findings in an oral presentation today.

The median duration of response (DOR) and progression-free survival (PFS) have not yet been reached.

Ten patients discontinued treatment during the study due to progressive MCL, all of whom had Ki-67 levels greater than 60% (range 50-100%). There were no deaths due to toxicity. Grade 1 hematologic toxicity events included anemia (30%) and thrombocytopenia (25%). The most common treatment-emergent, non-hematologic adverse events (occurring in >15% of patients treated with IMBRUVICA plus rituximab) included fatigue; diarrhea; myalgia and dyspnea. This combination has been well tolerated.

Abstract 1998: Addition of Rituximab Abrogates Ibrutinib-Induced Lymphocytosis and Promotes More Rapid Decrease in Absolute Lymphocyte Counts in Patients with Relapsed Chronic Lymphocytic Leukemia

Additionally, data from a multi-center, Phase Ib/II trial also suggest that when IMBRUVICA and rituximab are combined in patients with relapsed CLL, short-term lymphocytosis, which sometimes is associated with IMBRUVICA treatment, decreased and patients experienced faster clearing of leukemia cells from the bloodstream versus patients who received IMBRUVICA alone. These data were presented in a poster presentation on Saturday, December 6^th by Ekaterina Kim, M.S. from The University of Texas MD Anderson Cancer Center.

The median absolute lymphocyte count (ALC) during pre-treatment was similar in the IMBRUVICA single-agent and combination treatment arms (25 and 27.6 K/µl, respectively). In the IMBRUVICA single-agent arm, ALC levels rose immediately after treatment was started and began to stabilize. After four months of follow-up, patients in the combination therapy arm experienced a more rapid decrease in ALC levels, suggesting the combination decreased lymphocytosis over this period. Plasma levels of chemokines CCL3 and CCL4 are known to reflect the activation status of CLL cells. Concentration of both chemokines was significantly reduced after a week of treatment in both arms. Further analysis of the CCL3 and CCL4 patterns is still in progress.

No additional safety findings were reported.

Additional data on the combination of IMBRUVICA and rituximab previously were presented at the German Society for Haematology and Medical Oncology annual meeting in October 2014 and published in The Lancet Oncology in August 2014.