MDACC has, for the first time, given their experience of TKI
6 ^2 J$ [* \& H/ K& Ndiscontinuation. The doctors at MDACC look at 26 patients who
: ^4 v& T7 i: P4 idiscontinued therapy from 2003-2012 for various reasons. These reasons2 d7 ~* H+ O4 K$ \: c0 I
include long time in CMR, adverse side-effects, pregnancy and financial
* M s4 a z% |4 ~( Cconstraints. Please note that 17 patients discontinued therapy in CMR' [' D0 I* w8 _! n. H$ m1 M: j
and the rest in MMR. Of the patients in CMR who discontinued therapy,- W6 ~5 d" i4 D8 H9 |
47% had molecular relapse. Those in CMR who discontinued and had taken
' e2 D. w: U7 q2 c7 Zprior Interferon to a TKI, 50% relapsed. Also note that of these 26
' l- y6 |1 z+ i# h; W% k ]5 epatients, most had been treated with high dose Gleevec./ X6 @ f6 t# M0 N
4 U% b1 G; r! @5 C0 g* y; V, c"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17
5 I! V9 ?& \$ [/ A(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.! \) p& j# P, L9 r) u1 i9 z- n& h
The median duration of CMR before TKI cessation was 62 mos, (0- 118). ]" B2 \- D& Z/ i1 \
The median duration of total TKI therapy was 101 mos (3- 135)."
/ K2 P4 W1 k/ v, Z
0 g( v# K4 _% x3 tTherefore, the median time in CMR before discontinuation was about 5, u" ^. h& D9 J8 ]; I
years. The median follow-up is only 11 months. The median time for$ M- Y$ v& C7 e T
molecular relapse of 8 patients who had been in CMR was 4 months and( M3 q6 w7 n7 S+ m8 D' d) S
they relapsed with median PCR value of 0.01 on the International Scale.( p/ Z+ j* m: m5 j
$ u6 M3 ` M: H1 w+ x, _
Of the 7 patients who discontinued when in MMR, 4 remained in MMR at a
7 A# @+ [4 W( ]median follow-up of 21 months, 1 remained in CCR, 1 in active disease
8 g2 r3 M- R3 E) L5 iand 1 transformed to accelerated phase off drugs. Therefore, from this
N6 I2 P- }/ L- y' ~8 {data, scarce as it is, there is a risk of transformation to advanced
. ?4 g! a3 h9 y8 }) C# ?) S9 kdisease if one discontinues drugs in MMR.
" p, f* \3 U# \8 Q; y) f) `
; n0 T' l: e+ K+ D. F9 k: e5 y4 k2 patients were PCRU (4.5 log machine) and these patients relapsed
( d; ~. ~' ?6 L& f1 Ainto MMR when drugs were discontinued.* j' H( @! z0 d+ X# [# l
8 W8 h: x8 [. aSeven pts with relapse were treated again with TKI, 3 with nilotinib,% y/ e! e6 ^) e; e1 q6 ?* {' i
2 with dasatinib, and one each with imatinib and bosutinib (the latter
3 Y- d: z; w9 ~3 |" ^( _$ Xin AP). After a median of 13 months on therapy (range 4-52) all patients
% W# T0 @! A4 v% m7 r2 X4 mimproved their response, 5 with CMR and 2 MMR (including the pt that had
7 Y4 R) W+ ?& \4 q1 e3 R: ltransformed to AP). They do not say why all patients were not retreated9 G9 N# H' Y q* m
with imatinib and had to take Nilotinib and Dasatinib. Also, note that- R3 H) g" S, {6 m; q3 i, _# T
one did not regain CMR at the 13th month mark though it is good news+ _) i; I" ~/ N' r. l- Y
that 5 did. It may take some time to regain CMR for some who have gone1 ^- T( ^! {# K& }- y2 y
off drugs and relapsed. However, from our own list experiences, some
' Q# ?2 g- d+ g) c( V$ Ohad regained CMR fast when they retook the TKI.
6 P) e) P- h e$ t' d3 v' T9 ~& S/ q" u$ B
The doctors conclude that treatment discontinuation is experimental8 C4 `9 r2 s; |
and cannot be recommended at this stage as a standard procedure.+ N: t' I3 a) Q: N! }
9 ]2 ?- x. c- W' I/ pBest Wishes,
9 U' ]4 v7 p0 |4 t. K m
1 m2 r" U2 h0 I2 ]( KAnjana
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3 A0 V! ]; l- U- l( N
% X I1 X. ?' D/ E; E2 |) {$ M% }, w& x+ y1 n( p2 w. G* F
r/ S7 E: L" z; j3 L4 _2 L. |
0 f+ X0 g( f4 \5 ]
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7 s' ]$ Z3 H2 k0 o" @
; z7 S- z- n; N6 g% d( ?0 Y3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor
; Y2 {7 M% N3 `% k* B0 cTheray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single
" q6 s1 k8 k1 G/ L0 I9 \Institution Experience
( A, q1 F$ ^( f+ J$ b& t0 }Program: Oral and Poster Abstracts
9 {7 v& I/ E* |& i- K/ YSession: 632. Chronic Myeloid Leukemia - Therapy: Poster III( i* R, J: ]5 Y5 i: G/ e- u
( {+ k" R" M& q$ F0 w9 HMonday, December 10, 2012, 6:00 PM-8:00 PM
# n1 P6 |" z# c
; H/ a9 [# @% pHall B1-B2, Level 1, Building B (Georgia World Congress Center)$ q8 u s% M+ D' V
7 X ]# x" V9 q0 a1 p/ v0 jOhad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,4 Z. h2 o; s' }6 Y E5 g
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,2 |1 v" t8 L4 ]# ]
Stefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,* K( O3 H$ u2 J8 W4 T- e$ L
Gautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.5 m! o7 A: c0 r, o' C) Z$ K( d
Cortes, MD1; p6 j) K4 Q b# j }
& Q" O* i# Y c0 W2 `: T1Department of Leukemia, The University of Texas MD Anderson Cancer
3 L( `4 p! f; |3 ^# s8 K5 ^2 cCenter, Houston, TX
3 D( R* a V: O3 q; ^) f1 A2Department of Leukemia, The University of Texas M.D. Anderson Cancer1 {! o5 Y4 h8 e# e; e
Center, Houston, TX
% N. T$ C6 M$ t" H! k" x" C& V$ j; _8 o7 ]. J
Introduction: Some recent studies have reported on the outcome of CML# C7 t* V" y7 i: X
pts who discontinued thyrosin kinase inhibitors (TKI) after achieving
$ Q4 |0 t7 p* B9 ]2 H* |sustained undetectable bcr-abl transcript level. Most patients who stop
/ r. u% r. `: s! M6 S" gTKI have experienced molecular relapse. Most patients respond after
4 F$ ?9 F, @( T% v% E6 [* cresuming TKIs regaining undetectable bcr-abl transcript levels. These/ u1 j2 r' E, V. z( x* O5 h
series have prospectively planned treatment discontinuation and included
( D/ {3 T9 H+ Fonly pts that have sustained complete molecular response (CMR) for at
/ I- I1 L* E; W& mleast 2 yrs. However, in many instances pts may want to discontinue TKIs: X% \; x1 e, \+ d) T2 Z2 |
not in CMR. Various reasons may lead patients to discontinue TKI |5 h$ t7 Q; Z( t$ E
treatment unexpectedly, among them severe adverse effects, pregnancy or
2 c+ F2 h0 c6 x$ Seconomic constraints. This single institution experience reflects the
' o" s: o- U; J* G- O3 N4 c: i# M0 theterogeneous nature of pt-driven TKI discontinuation.2 i. N7 w2 Y( |( y6 P
( I- J1 Z2 K2 f$ G/ q% R" }; t
Aim: To characterize the outcome and profile of CML pts who chose to" X$ ^# ~* P8 Z0 J1 h! E) B
discontinue TKI therapy in a single center regardless of their initial
/ Y: X) o+ z. e* R9 ?1 Lresponse to TKI therapy.2 ~/ C# v% l0 t& z+ G- P: A% }
( H0 o3 w3 G( \! I0 s# r% p0 c: J
Methods:We retrospectively analyzed MDACC data on all patients with CML. x# z7 }& v8 J! J
that were treated with TKIs in our institution and discontinued therapy.3 S F3 h5 J( R( C0 L7 q7 m. _3 F
: |. |& z$ }$ N# rResults: A total of 26 patients with CML-CP managed at MDACC
0 f. t- P) N, x8 g* Ediscontinued TKI between 2003 and 2012. The total median follow up time
" ]3 i$ I: u. ]. a$ N2 _since diagnosis was more than 120 months (mos) (range, 45 mos to 304
( n& d4 b/ f7 y( `- xmos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
$ H& A) P5 A) [$ H; f5 _% mfemale. All pts had been diagnosed and treated in chronic phase.2 B% X% Z8 E" n) v8 z+ j- T% t
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI+ k" k, S6 H S7 X
as initial therapy (4 received imatinib 400mg/day, 10 imatinib
: C, u7 W/ i3 `+ N+ l, Y1 I5 o600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with0 G5 t, V, L4 S9 P5 t
IFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN
% {2 \+ _. ^9 p8 @failure. Pts treated frontline with TKI started therapy within a median
: p# c: E6 Y- `* l/ H. {! R0 b: ~of 0.8 mos from diagnosis (range 0 to 4) and those with previous
* u4 i6 E( p! i( ninterferon (n=11) after a median of 60 mos from diagnosis (31 to 1643 A$ i0 f) x. k
mos). Before TKI discontinuation 21pts (81%) were receiving their first5 p; Y" b+ i" I+ a
TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete
2 J% a5 X+ C& l2 q2 B. ocytogenetic response (CCyR) had been achieved in all 26 pts at a median$ R p1 f% K% i" ?+ C2 I
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of% n& M. e) A: C6 Z0 R( {
9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All
7 d, u& K2 a$ @3 Lpatients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)& V. B! r& ^% ^1 U
had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The0 s) i1 s$ x- _9 v7 x, q$ T) R
median duration of CMR before TKI cessation was 62 mos, (0- 118). The
/ O0 G! e0 `5 m umedian duration of total TKI therapy was 101 mos (3- 135).9 b9 [9 b, O7 z0 A
7 C: j0 I; ^8 m' Z! C. \
Fourteen pts (54%) discontinued TKI due to adverse events, 2 pts
) H5 R* { V6 Ndiscontinued to become pregnant, 5 decided to stop after long CMR, and 5
( G, p0 |) s [6 o2 a& U; g( Kpts discontinued for financial reasons. After TKI discontinuation
( Q8 ^- z6 \: L. b) f( wpatients were followed for a median of 11 mos (5-131). Among pts with
1 K! v }( p1 T9 c9 `CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a5 \5 a7 r/ k# N" q4 T! \
median of 4 mos (1-11) from discontinuation with median transcript level
& ?1 ~* L b5 L1 V( J6 Mat relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF
/ w0 l7 F$ T9 J" M" }1 X6 \% Otherapy had CMR at time of TKI discontinuation, 50% of them relapsed. k& J. H# }& p7 D3 C
Among 7 pts who discontinued therapy in MMR, after a median follow-up" D( e1 |, Q: U& J2 Q* |2 S
from discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
9 n' @ E* q/ ^" w, J/ A- \2 Eone has minor CyR and one CCyR without retreatment at last follow up
8 p0 E* p( n0 ?/ _ _0 o7 }after 78 and 105 months from TKI discontinuation, and one transformed to
! B8 W2 K, D) \4 v% O$ G0 B8 Daccelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
6 w6 ^. ]; O0 x" H( E$ O. \2 Vto MMR. Three pts had a transient molecular recurrence with spontaneous
# q) e* S0 d3 Dre-gain of CMR. Seven pts with relapse were treated again with TKI, 35 g, D* Y( ?9 D+ D8 P- J
with nilotinib, 2 with dasatinib, and one each with imatinib and j3 Q! Q2 T, ]5 K+ r) _
bosutinib (the later in AP). After a median of 13 months on therapy9 M% L0 B8 P. B5 U
(range 4-52) all patients improved their response, 5 with CMR and 2 MMR
% A: V) X% X/ A* T9 i(including the pt that had transformed to AP). There were no deaths or2 A4 @! V& N; F% W i
transformations to blastic phase of CML. At last follow up 14 (54%) pts
( P8 o& r# N" U+ B; F$ {; \were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
% V2 w; {; F( _7 f5 KPCyR.
9 j# z6 h" s- |7 ~' {
- u ~' D# A8 IConclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular
+ I+ T3 w X5 srelapse in nearly half of the pts who discontinue therapy in CMR. Some
! u( U, z; y% v- gpts who discontinue in MMR may have sustained MMR. Treatment! I+ a# V& A& K( ?
discontinuation should be considered experimental and cannot be9 F( N8 {4 U: a4 j) D
recommended to pts as a standard approach.; R- h$ ~! V1 t1 P$ X9 x2 {
* [& R5 Q6 `8 z* \. H/ N G
Disclosures: Ravandi: BMS: Honoraria, Research Funding. |