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ASH 2014: Ibrutinib Demonstrates Clinical Activity in Relapsed or Refractory Multiple Myeloma

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Key Points

According to new data reported at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, ibrutinib demonstrated antitumor activity both as a single agent and in combination with dexamethasone in heavily pretreated patients with relapsed or relapsed/refractory multiple myeloma.

According to new data reported at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, ibrutinib (Imbruvica) demonstrated antitumor activity both as a single agent and in combination with dexamethasone in heavily pretreated patients with relapsed or relapsed/refractory multiple myeloma (Abstract 31).

Phase II Trial

The open-label, phase II dose-escalation trial evaluated potential ibrutinib dosing regimens either as a monotherapy or in combination with dexamethasone at 40 mg in the treatment of 69 heavily pretreated (relapsed or relapsed/refractory) patients. Efficacy and safety were assessed at 4-week intervals using the International Myeloma Working Group (IMWG) response criteria for efficacy results and Common Terminology Criteria for Adverse Events (CTCAE) to evaluate safety.

Heavily pretreated patients (median of 4.5 prior lines of therapy) who received ibrutinib 840 mg daily in combination with dexamethasone 40 mg weekly (n = 20) experienced the highest clinical benefit rate of 25%, including one partial response and four minor responses. An additional five patients (25%) showed sustained stable disease for more than four cycles. The combination treatment resulted in a median progression-free survival of 5.6 months.

As a result of this trend toward improved efficacy and manageable toxicities, investigators expanded the treatment group per protocol design. Twenty-three additional patients are currently enrolled in this cohort, and follow-up is ongoing. Based on these encouraging data, ibrutinib is currently being evaluated as a combination agent to treat relapsed/refractory multiple myeloma with agents such as carfilzomib.

Adverse Events

The safety profile of ibrutinib was tolerable, with similar adverse event rates across dosing cohorts. Across all cohorts, 57% of patients experienced grade 3 or greater adverse events. The most commonly reported nonhematologic adverse events of any grade were diarrhea (51%), fatigue (41%), nausea (35%), dizziness (25%), and muscle spasms (23%). Myelosuppression had an overall incidence of any grade anemia (29%), thrombocytopenia (23%), and neutropenia (7%), with 16%, 9%, and 4% being grade 3, respectively. There were no clinically meaningful differences among dose levels.

Thirty-three percent of patients experienced a treatment-emergent serious adverse event. At the time of data cutoff, four patients remained on treatment; the most common reason for treatment discontinuation in 47% was progressive disease.

The study was sponsored by Pharmacyclics. For full disclosures of the study authors, view the study abstract.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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