ATLANTA—The oral Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has an “unprecedented single agent overall response rate” in patients with relapsed or refractory mantle cell lymphoma (MCL), interim results of a global phase 2 study reported during the 54th American Society of Hematology Annual Meeting and Exposition.

Preliminary results reported at last year’s meeting showed ibrutinib achieved rapid nodal responses, including complete responses; the current data confirm “responses to ibrutinib increase with longer time on study treatment,” said Michael Wang, MD, of the Department of Lymphoma/Myeloma and Stem Cell Transplantation/Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.

The study enrolled 115 subjects with relapsed or refractory MCL between February 15, 2011 and March 21, 2012 at 18 sites, 9 in the US and 9 in the EU; 110 were evaluable for efficacy, 63 of whom were bortezomib-naïve and 47 who were previously exposed to at least 2 cycles of bortezomib. Data cut-off was September 21, 2012.

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Median age was 68 years (range, 40-84 years), median time since diagnosis was 42 months (range, 3-224 months), median number of prior treatments was 3 (range, 1-6 treatments), 13% had bulky disease (≥10 cm), 29% had received hyper CVAD, 10% had a prior stem cell transplant, 49% were deemed high risk by MIPI score at baseline assessment, and 45% had refractory disease.

Patients received ibrutinib 560mg/day in continuous 28-day cycles until disease progression.

“Bortezomib-naive and bortezomib-exposed cohorts were evaluated separately,” Dr. Wang reported, with tumor response assessed every 2 cycles according to the revised International Working Group for NHL criteria.

At a median follow-up of 9.2 months, best response was 65% in bortezomib-naïve patients (21% complete response [CR] and 44% partial response [PR]) and 72% in those previously exposed to bortezomib (23% CR and 49% PR); total best response was 68% (22% CR and 46% PR).

Time to CR ranged from 1.7 to 16.4 months (median, 5.5 months) and time to PR, 1.4 to 9.1 months (median, 1.9 months). Longer follow-up of the initial 51 subjects reported at ASH 2011 demonstrates the durability of responses, Dr. Wang noted, adding that median time on study treatment was 3.7 months and is now 14.7 months; best response was 69% and is now 75%; CR rate was 16% and is now 39%.

Median duration of response has not been reached; median progression-free survival (PFS) is 13.9 months.

Adverse events (AEs) occurring in >10% of 111 subjects were diarrhea, fatigue, upper respiratory tract infections, nausea, rash, dyspnea, and peripheral edema. Treatment-emergent infectious AEs grade ≥3 included pneumonia, cellulitis, sepsis and urinary tract infection. Treatment-emergent hemorrhagic AEs of all grades occurring in ≥2% of patients included contusion, epistaxis, petechiae, ecchymosis, hematuria, subdural hematoma, and purpura.

A pivotal study in patients with relapsed and refractory MCL treated with bortezomib is underway.