In a study of 116 patients, the overall response rate (ORR) was 68 percent in elderly treatment-naive (TN) patients with an estimated 96 percent progression-free survival (PFS) rate at 26 months. In patients with RR CLL/SLL, including those with HR disease, the ORR was 71 percent with an estimated PFS at 26 months of 75 percent.
A second study in 40 patients with HR CLL treated with the combination of ibrutinib and rituximab therapy reported an ORR of 83 percent, with 38 of the 40 patients continuing on therapy without disease progression. Patients with HR disease have inferior responses to standard chemo-immunotherapy and shorter rates of PFS and OS.
These findings, from ongoing Phase 1b/2 and Phase 2 trials, were presented in a press briefing today at the 54th annual meeting of the
In describing the findings of the Phase 1b/2 ibrutinib monotherapy trial, lead investigator
In his presentation, Dr. Byrd noted that current therapies have a number of limitations in terms of how long they can be used in a patient and their tolerability, especially in elderly patients. "Further, virtually all patients relapse, and there are few salvage regimens that produce durable remissions," he pointed out.
The Phase 2 trial, evaluating ibrutinib in combination with rituximab, was led by
"We are very excited by the response rates we saw with ibrutinib-rituximab combination therapy, and believe they emphasize the need for rapid, further development of ibrutinib, especially for patients with high-risk CLL/SLL," said Dr. Burger.
Studies and Findings
Oral presentation 189, The Bruton's Tyrosine Kinase (BTK) inhibitor ibrutinib (PCI-32765) promotes high response rate, durable remissions, and is tolerable in treatment naive (TN) and relapsed or refractory (RR) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) patients including patients with high-risk (HR) disease: New and updated results of 116 patients in a phase Ib/II study
This presentation was based on findings from a Phase 1b/2, multi-center trial with 116 patients with TN (n=31), RR (n=61) or HR (n=24) CLL/SLL. Patients were treated with oral ibrutinib monotherapy, either 420 mg or 840 mg daily. Patients with RR disease had received at least two prior therapies; patients with HR disease had relapsed within two years following chemo-immunotherapy. The study objectives were to determine the ORR, PFS, overall safety (OS), safety of the two dosing regimens and pharmacokinetics/pharmacodynamics.
Responses were independent of high-risk clinical or genetic features, such as a deletion of part of chromosome 17 (del17p).
Most adverse events (AEs) were Grade 1 or 2 in severity, with the most common attributed to ibrutinib being diarrhea, fatigue, nausea and rash. Adverse hematologic events were relatively infrequent. In patients with cytopenia (low blood cell counts) at the beginning of the study, sustained improvements of platelet counts (78 percent) and hemoglobin (82 percent) were seen after treatment. There was no evidence of cumulative toxicity or long-term safety concerns.
Oral presentation 187, The BTK inhibitor ibrutinib (PCI-32765) in combination with rituximab is well tolerated and displays profound activity in high-risk chronic lymphocytic leukemia (CLL) patients
This presentation was based on findings from a Phase 2, single-center trial with 40 patients with HR CLL treated with 420 mg/day ibrutinib in combination with rituximab, a current standard CLL therapy. Patients with HR disease were previously treated and had one of the following characteristics: deletion of a part of chromosome 17 (del17p), which is associated with poorer treatment outcomes; a gene mutation called TP53; del11q, another partial chromosome deletion associated with poorer outcomes; or a short remission duration (less than three years) after first-line chemo-immunotherapy.
The results after a follow-up of three to six months are:
"We believe the updated findings from these two trials further affirm the possibilities of ibrutinib," said
About Ibrutinib
Ibrutinib was designed to specifically target and selectively inhibit an enzyme called Bruton's tyrosine kinase (BTK). BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel — regulating B-cell apoptosis, cell adhesion, and lymphocyte migration and homing. Data are consistent with a mechanistic model whereby ibrutinib blocks BCR signaling, which drives cells into apoptosis and/or disrupts cell migration and adherence to tumor-protective microenvironments.
The effectiveness of ibrutinib alone or in combination with other treatments is being studied in several B-cell malignancies, including CLL/SLL, relapsed/refractory mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma and multiple myeloma. A comprehensive late stage Phase 2 and 3 program is under way.
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Note: Data in this release correspond to ASH Abstracts 189 and 187.
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