Conference Coverage

Ibrutinib, palbociclib yield durable complete responses in pretreated mantle cell lymphoma

 

Key clinical point: Combination therapy with ibrutinib and palbociclib was generally well tolerated and induced complete responses in patients with pretreated mantle cell lymphoma.

Major finding: A total of 44% of patients had complete responses, and 67% remained alive and progression-free after a median of 11 months of follow-up. Severe rashes occurred at the highest dose studied (420 mg ibrutinib/100 mg palbociclib).

Data source: A phase I trial of 20 patients with previously treated mantle cell lymphoma.

Disclosures: The National Cancer Institute sponsored the study. Dr. Martin disclosed ties to Janssen, which makes ibrutinib, and to Celgene, Gilead, Novartis, Acerta, and Teva. Senior author John P. Leonard, MD, and one of 10 coinvestigators disclosed ties to several pharmaceutical companies.


 

AT ASH 2016

– A “mechanism-based” combination of ibrutinib and palbociclib was reasonably well tolerated and induced complete responses in 44% of patients with previously treated mantle cell lymphoma, Peter Martin, MD, reported at the annual meeting of the American Society of Hematology.

Single-agent ibrutinib (Imbruvica) has shown promise in mantle cell lymphoma, but treatment failure affects about half of patients within 1 year, Dr. Martin noted. The CDK4/6 inhibitor palbociclib (Ibrance) induces prolonged arrest early in the G1 phase of the cell cycle, which overcame ibrutinib resistance in mantle cell lymphoma cell lines in a prior study (Cancer Discov. 2014;4[9]:1022-35).

To test the maximum tolerated dose of combination therapy, Dr. Martin and his associates enrolled 20 adults with previously treated mantle cell lymphoma who were naive to ibrutinib and CD4/6 inhibitors. The patients had received a median of one and up to five prior lines of therapy, and six (30%) were refractory to their most recent therapy. They received ibrutinib daily and palbociclib on the first 21 days of each 28-day treatment cycle. Dosing began at one of five levels, ranging from 280 mg ibrutinib/75 mg palbociclib to 560 mg ibrutinib/125 mg palbociclib. Doses were escalated based on a standard phase I 3+3 design.

Among 18 patients evaluated, 12 (67%) responded to treatment, and 8 (44%) had a complete response. Median time to complete response was three cycles. The most common grade 1-2 adverse events were diarrhea, fatigue, rash, and bruising. Three patients (15%) developed dose-limiting toxicities. These included one case of grade 4 thrombocytopenia at 420 mg ibrutinib/100 mg palbociclib and two cases of grade 3 rash at 560 mg ibrutinib/125 mg palbociclib. The grade 3 rashes led to dose reductions, and six patients needed dose interruptions. Also, four patients stopped treatment because of disease progression, two did so because of elevated liver enzymes or prolonged cytopenia, and one did so to undergo allogeneic stem cell transplantation.

The National Cancer Institute sponsored the study. Dr. Martin disclosed ties to Janssen, which makes ibrutinib, and to Celgene, Gilead, Novartis, Acerta, and Teva. Senior author John P. Leonard, MD, and one of 10 coinvestigators disclosed ties to several pharmaceutical companies.

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