Crizotinib Produces Durable Responses in Small Study of Patients With Advanced, Chemoresistant ALK-Positive Lymphoma
In a brief communication in the Journal of the National Cancer Institute, Passerini et al described compassionate use experience with the ALK inhibitor crizotinib (Xalkori) in a group of patients with chemoresistant advanced ALK-positive lymphoma. Response was observed in 10 of 11 patients, and treatment was well tolerated.
Study Details
The study included 11 patients with refractory or relapsed ALK-positive lymphoma after at least one prior chemotherapy regimen, and measurable disease. Patients received crizotinib at 250 mg twice daily until disease progression. Patients ranged in age from 19 to 55 years and had stage IIB to IVB disease; nine patients had anaplastic large cell lymphoma, and two had diffuse large B-cell lymphoma. Ten patients had received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and nine had received three or more prior treatments.
Responses
The overall response rate was 10 of 11 (90.9%, 95% confidence interval [CI] = 58.7%–99.8%). At the latest follow-up, four patients remained in complete response at > 21, > 30, > 35, and > 40 months with ongoing continuous crizotinib treatment. Four patients, including two with anaplastic large cell lymphoma and both patients with diffuse large B-cell lymphoma, had disease progression at 1, 2, 2, and 2 months.
One patient achieved complete response on crizotinib, received an allogeneic bone marrow transplant, and remains in complete response. Another two patients treated before or after allogeneic bone marrow transplantation remain in complete response but have stopped crizotinib treatment. In two of the four patients with progression, the kinase domain of NPM/ALK could be amplified from peripheral blood samples obtained at the time of relapse, with deep sequencing showing presence of ALK mutations.
Two-year progression-free survival was 63.7% (95% CI = 30.8%–89.1%) and 2-year overall survival was 72.7% (95% CI = 39.1%–94.0%), with plateaus in both survival curves after the initial 2 months of follow-up.
Adverse Events
All crizotinib-related toxicities were grade 1 or 2 and included ocular flashes in 10 patients, peripheral edema in 3, skin rash in 1, and erectile dysfunction in 1. Laboratory abnormalities included neutropenia in two patients and thrombocytosis and elevated liver function tests in one patient each. No patient died from a treatment-related cause, and no treatment-related adverse events led to treatment discontinuation.
The investigators concluded, “Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK[-positive] lymphoma patients, with a benign safety profile.”
Carlo Gambacorti Passerini, MD, of University Milano-Bicocca, Monza, Italy, is the corresponding author for the Journal of the National Cancer Institute.
The work was supported by grants from Associazione Italiana Ricerca sul Cancro, Lombardy Region, Lombardy regional government, and Fondo Sociale Europeo “Dote ricercatori”.
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