Vorinostat reduces graft-versus-host disease in stem cell transplant patients

jack1381818

December 3, 2013: r' _! Z2 q; m

) j* m' P' I& l/ J1 r1 b. f7 r
8 P& J. y! K! [/ Q0 \% l(dailyRx News) Stem cell transplants are potentially curative treatments for blood Cancer patients. But a common side effect of this procedure, called graft-versus-host disease, can be very serious, even deadly.+ G" ?  \) |, j2 U# Y. O0 b

  G/ g6 R: B- ^5 g4 l7 |# }
6 u9 C, P5 ?2 n- f1 ~! U4 w6 t& V* z, G7 f
A small trial showed that Zolinza (vorinostat) halved the incidence of graft-versus-host disease following stem cell transplants in patients with blood cancers.- p- h3 c  \1 N- u1 V. ^) W

& ~5 T# d% u( x- o2 XThis study found that when combined with other standard medications given with a transplant, Zolinza was safe for patients whose transplant used stem cells from close relatives.
) M% v; ]! F' C" c! M& F! {2 c% _" Z) O( p( H# ?. D* X8 W
This trial led by Sung Choi, MD, assistant professor of pediatrics at the University of Michigan Medical School, was designed to test the safety of Zolinza given to patients who had undergone a stem cell transplant to treat blood cancer.# P- U1 }& b  t. H0 G4 u$ g

9 r$ S" K  e! Q6 Y: H$ f, QIn a stem cell transplant, healthy cells are injected into the patient's body to replace damaged blood cells, such as those affected by cancer.
, Q0 U- G7 @, `5 |, q8 C; _8 A( T/ u) W3 b
Stem cells can come from the patient’s own blood or bone marrow. This is known as an autologous stem cell transplant. Stem cells can also come from donors, and these are called allogenic transplants.
- {5 M' Z5 H: o' V  C9 W8 Q+ k6 d8 ^7 f- k
Despite advances in the transplant procedure, graft-versus-host disease (GVHD) continues to be a serious complication that can be lethal.* G: q7 Z& r' F- Y, G' H% B" H; y
$ L; {. Z6 H1 [/ s( H: j
GVHD occurs when the newly transplanted donor cells start attacking the patient’s cells. The disease can be short-term (acute) or last for the rest of the patient’s life (chronic). Chronic GVHD can cause a host of problems ranging from vision changes to fatigue, muscle weakness and ongoing pain.
1 M! n, N' Q) Y& L; s  `
" T  U4 ~* B, K3 _/ a* G2 G2 u" O"Graft-versus-host disease is the most serious complication from transplant that limits our ability to offer it more broadly. Current prevention strategies have remained mostly unchanged over the past 20 years,” Dr. Choi explained in a statement.) U; h. W# H4 _& U, d# v& H

4 [* r* {) B: RIn this trial, Zolinza was given to 50 patients who had undergone a stem cell transplant that used cells from a close relative. The medication was given along with other standard medicines used with transplants, including fludarabine (brand names Fludara, Oforta), busulfan (Busulfex, Myleran), mycophenolate mofetil (Myfortic) and tacrolimus (Astagraf, Hecoria, Prograf, Protopic).
) r: @. Q7 k0 C6 E! D- M2 X! ?/ w. G3 |
Zolinza, an oral medication which is approved to treat T-cell lymphoma (a type of cancer that starts in white blood cells), was given for 21 days. Zolinza works by blocking histone deacetylases, enzymes that regulate various genes involved in the cancer process.
3 E6 q0 D# E+ g
& E; M9 B5 M- ?This research team found that 22 percent of patients who received Zolinza, combined with other standard medications, developed acute GVHD 100 days after the transplant, compared to 38-60 percent of transplant patients who typically develop acute GVHD.
  l, `% [3 z) J
5 U  K, g! |5 Z* H$ q3 R: t) a2 DParticipants were followed for a median of 26.3 months. After one year, 45 percent of the study members had developed moderate-to-severe chronic GVHD.
& _4 }3 P0 q. U8 C( Z+ W9 M) F8 d* ~/ Z2 S% N. p% T! ?+ c
One serious side effect related to Zolinza was high blood pressure. Other side effects were well-tolerated by the study members, the researchers learned.7 A% o) `, D8 I8 I( m4 ^
7 \/ j7 T7 X. O( H; O
"Vorinostat has a dual effect as an anti-cancer and an anti-inflammatory agent. That's what’s potentially great about using it to prevent graft-vs.-host, because it may also help prevent the Leukemia from returning," senior study author Pavan Reddy, MD, co-director of the hematologic malignancies and bone marrow transplant program at the U-M Comprehensive Cancer Center, said in a statement.
8 V9 p0 E1 p0 B% [! o
/ ]* q0 n# M. @6 t/ cFurther study is necessary to confirm these findings in other transplant settings. Trials are under way to evaluate if Zolinza can prevent GVHD in transplants involving an unrelated donor.) ^4 {/ U1 }# t- }) L& A8 B

, D4 m% P9 x1 p; m- e' `Results from this trial were published December 2 in The Lancet Oncology.
7 ]- G4 y1 J' R7 y- K  J2 a: E& I+ D
Merck, the manufacturer of Zolinza, supported this trial along with the Leukemia and Lymphoma Society, National Institutes of Health, St Baldrick’s Foundation and the Michigan Institute for Clinical and Health Research.
& o* z3 ?" R0 s# ?9 z. O! r( J, R* l* J# e5 d8 n; U9 _
No conflicts of interest were declared.8 P4 m6 O8 a: ^3 T

2 j# @0 n$ q* P& a5 D" L! `& e* a% ~
5 }8 X0 e! N4 w4 |( g& S# @# YConditions: 6 Y* z. ]1 n. T! M' @
Cancer Blood Cancer Hematology * g5 d$ K6 G0 S7 D0 z% Y: M8 P

) r2 g8 f3 U' ]) j% gMedications: % Q8 O$ `% @4 c  Z! |
Mustargen Prograf Protopic