T-cell lymphomas comprise 10-15% of newly diagnosed lymphomas. While a number of therapies are available for patients (pts) with relapsed and refractory disease, there is still an unmet need for novel agents and approaches. Sorafenib is a multi-kinase inhibitor that is approved for clinical use in renal cell and hepatocellular carcinoma. Molecular targets of sorafenib include B-raf, PDGFR, and VEGF. Recent studies have demonstrated overexpression of PDGFR and VEGF in Peripheral T-cell Lymphoma (PTCL) and Cutaneous T-cell Lymphoma (CTCL).1 We report results of a pilot study of sorafenib in patients with relapsed T-cell lymphomas.
Twelve patients with refractory T-cell lymphomas including 2 PTCL (one pt relapsed after allogeneic transplant and one after autologous transplant), 1AITL, and 9 CTCL ( stages IB=1, IIB=3, III-2, IV=3) were treated with sorafenib at a starting dose of 400 mg twice daily. Median age was 69 (range: 38-85). Seventy-five percent were female; 25% presented with B symptoms. The clinical activity of the drug was assessed by determining response rate, progression free survival, and duration of response or stable disease.
Four patients (33%) had a CR (skin and/or nodes), including one with PTCL and one with AITL, 3 (25%) had a CR in the skin, including one Stage III CTCL and two with PTCL with skin involvement. In addition, 2 (17%) had a mixed response, including one Stage IIB and one Stage III CTCL. Two patients had SD, including one with Stage IIB and one with Stage IB CTCL. Dose reduction from the starting dose of 400 mg twice daily occurred in 66% (8) patients: dose reduced to 300 mg daily in 2 pts and 200 mg daily in 6 pts. Three patients discontinued the trial due to progressive disease (25%). Of the remaining pts, all but one had to discontinue the drug due to adverse effects. Skin toxicity from sorafenib occurred in 5 pts, including rash in 3 pts and fissuring and exfoliation of the palms and soles in 2 pts. The one pt with angioimmunoblastic T cell lymphoma had a clinical CR and was able to undergo an allogeneic stem cell transplant. Nine (69%) pts are still alive.
In this pilot study, Sorafenib demonstrated activity in pts with refractory T-cell lymphomas but dose modifications for skin toxicity occurred frequently, suggesting that a lower dose would be more tolerable. We plan to conduct a follow up study exploring lower doses of sorafenib and correlating clinical activity with tissue expression of ERK, PDGFR, and VEDGF.
1. Piccaluga PP, Agostinelli C, Zinzani PL, Baccarani M, Dalla Favera R, Pileri SA. Expression of platelet-derived growth factor receptor alpha in peripheral T-cell lymphoma not otherwise specified. The lancet oncology. Jun 2005;6(6):440.
Off Label Use: sorafenib in t cell nhl. Foss:celgene: Honoraria, Research Funding; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees; eisai: Membership on an entity’s Board of Directors or advisory committees; spectrum: Research Funding; merck: Research Funding; seattle genetics: Research Funding.
Asterisk with author names denotes non-ASH members.