MDACC has, for the first time, given their experience of TKI
* k ^- P% P1 w1 H, ~: @) H- bdiscontinuation. The doctors at MDACC look at 26 patients who
* ~4 T: w6 M. e6 T" G) cdiscontinued therapy from 2003-2012 for various reasons. These reasons
( _. H% k3 L# W+ I8 p4 qinclude long time in CMR, adverse side-effects, pregnancy and financial: G J% t8 Z4 |1 g0 d+ h
constraints. Please note that 17 patients discontinued therapy in CMR
0 L5 S5 R6 [( z6 w' O( Rand the rest in MMR. Of the patients in CMR who discontinued therapy,- y# ]# p! @) e* P5 B
47% had molecular relapse. Those in CMR who discontinued and had taken
9 K/ _: s. E* q( z' yprior Interferon to a TKI, 50% relapsed. Also note that of these 26
- T1 R( w8 U' T& kpatients, most had been treated with high dose Gleevec.% l5 r- P c e9 r: {9 R
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"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17
# G1 \5 T6 l W% q) Q' ]% J(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.
% n I8 }7 p( z8 }The median duration of CMR before TKI cessation was 62 mos, (0- 118).8 Y+ `9 h! D9 T" z2 i( W& S& W1 H+ T
The median duration of total TKI therapy was 101 mos (3- 135)."+ k# l$ v" k* @( I
, z: H9 Y. j1 f0 [Therefore, the median time in CMR before discontinuation was about 51 P: q1 R8 g: N: L
years. The median follow-up is only 11 months. The median time for
2 {. M) K$ C: D6 P1 omolecular relapse of 8 patients who had been in CMR was 4 months and
" `, f* s7 E' `. Zthey relapsed with median PCR value of 0.01 on the International Scale.& U& Q6 Y* p$ R- q' _& [0 U
: |- j4 c8 N5 @Of the 7 patients who discontinued when in MMR, 4 remained in MMR at a
, M3 q. @" l9 T! o. \median follow-up of 21 months, 1 remained in CCR, 1 in active disease
' Z6 j, ?& n+ j% V3 _, V8 x1 A' j3 }and 1 transformed to accelerated phase off drugs. Therefore, from this* \% m) G1 Z! j! V3 f* I
data, scarce as it is, there is a risk of transformation to advanced
3 m# [& b+ p3 _8 }% W7 Wdisease if one discontinues drugs in MMR.& y% M0 s) c/ M6 V
% ?$ F4 o' I0 ?& M( I6 V! |
2 patients were PCRU (4.5 log machine) and these patients relapsed
: O' z2 a: \- K# h# N' i- Iinto MMR when drugs were discontinued.
4 ~6 O n! {& c# W2 V2 ^: m
6 G( D- \$ {' }Seven pts with relapse were treated again with TKI, 3 with nilotinib,
+ `/ q) x7 @7 e$ q2 with dasatinib, and one each with imatinib and bosutinib (the latter4 }8 F, B+ L5 z% {' M' B, e4 H) N
in AP). After a median of 13 months on therapy (range 4-52) all patients
4 \# x/ Q2 E$ i5 u7 s1 |8 Iimproved their response, 5 with CMR and 2 MMR (including the pt that had# [; B( Q( H$ i% S7 W. i9 {, ?
transformed to AP). They do not say why all patients were not retreated& e+ B, J$ i) v3 H: u7 C
with imatinib and had to take Nilotinib and Dasatinib. Also, note that9 v( W3 u0 X; P, g& H
one did not regain CMR at the 13th month mark though it is good news$ G+ m' T. v2 @% s
that 5 did. It may take some time to regain CMR for some who have gone
- d" }+ R/ S& g) joff drugs and relapsed. However, from our own list experiences, some
. b3 v+ C2 K' `7 y9 k. Uhad regained CMR fast when they retook the TKI.
& g+ G. u5 o/ U1 h- |7 F6 V2 I2 H3 m8 Q& L# s! r
The doctors conclude that treatment discontinuation is experimental: l# z6 N) N3 f* R( m3 q
and cannot be recommended at this stage as a standard procedure.9 @6 X- E2 s( A! w+ ~$ p% B8 H
* ~' W4 y2 r& @3 W& z. k, h0 W1 ^! UBest Wishes,5 A! p6 [# \9 q0 Q) F: C: L
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Anjana1 I2 |% N* _3 B& `( s
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, e/ J4 E; c, V6 s+ p; q4 `3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor) r9 B6 c6 `0 W8 z
Theray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single
0 H% r# F" C) C) `1 E* pInstitution Experience
7 B5 S9 {, M, pProgram: Oral and Poster Abstracts
) `3 D' E, i/ V/ }2 P/ `Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III* e- h. k9 S/ d+ B( G j
5 h$ W$ b8 A e* e( D
Monday, December 10, 2012, 6:00 PM-8:00 PM
, l6 u0 `: V) J$ X S& D2 D u/ `" B& Z9 Q8 G/ D
Hall B1-B2, Level 1, Building B (Georgia World Congress Center). f0 J: X6 I; G' }% J
) y. K. R- L9 l6 M, \
Ohad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,
4 g$ c& [4 m |5 f* H4 f WElias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
8 i7 v3 z T; m& I" IStefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,) m- X2 K: {9 U& o
Gautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.
8 L& w" y( V" y& u& A, d. D5 zCortes, MD1
0 Q/ D7 p( U2 w3 U7 F, V& U; Z% p# z. [8 f' C
1Department of Leukemia, The University of Texas MD Anderson Cancer( J$ e1 P" e# A. O' t9 B' m; m
Center, Houston, TX$ E0 V; P1 h( a) O; ~7 W2 Y1 v
2Department of Leukemia, The University of Texas M.D. Anderson Cancer" G4 u* }" s! S5 L% k5 e7 w7 _
Center, Houston, TX/ y( d1 H5 r" _" i. l2 M1 k% z
! j1 |* f, }' m$ c7 ?Introduction: Some recent studies have reported on the outcome of CML
# X; v, O& X" m/ Vpts who discontinued thyrosin kinase inhibitors (TKI) after achieving
/ r1 n- D+ q4 L/ @sustained undetectable bcr-abl transcript level. Most patients who stop; U, P. N5 m1 g Y: c
TKI have experienced molecular relapse. Most patients respond after) e f; X( v" p6 _
resuming TKIs regaining undetectable bcr-abl transcript levels. These6 }1 h$ u& o1 I
series have prospectively planned treatment discontinuation and included% S9 J3 v9 L9 J" r" y/ `
only pts that have sustained complete molecular response (CMR) for at
2 j5 E$ Q* p& a* B, wleast 2 yrs. However, in many instances pts may want to discontinue TKIs
* N# [/ \. h$ a" snot in CMR. Various reasons may lead patients to discontinue TKI
8 L$ G% l8 ^0 i! Ltreatment unexpectedly, among them severe adverse effects, pregnancy or
1 _9 z0 S/ j' ^/ J ieconomic constraints. This single institution experience reflects the
Y7 i# I7 @: c- k: A2 x" |heterogeneous nature of pt-driven TKI discontinuation.% d# t# ]( u- X5 d1 l4 H
9 H; u0 ~6 p) |/ c$ K; B8 H# t
Aim: To characterize the outcome and profile of CML pts who chose to
0 K" b: G+ Z3 y" L. o3 Xdiscontinue TKI therapy in a single center regardless of their initial
0 O% H/ G. W3 \response to TKI therapy.: I( d* Q& _) O' o. G# N
! F0 s5 T" j( t# D
Methods:We retrospectively analyzed MDACC data on all patients with CML) ?2 R; i/ |3 S+ s# m) k
that were treated with TKIs in our institution and discontinued therapy.
8 t; u8 `( t) @$ G2 u' P0 ?1 J6 `& m% y0 O, v- j
Results: A total of 26 patients with CML-CP managed at MDACC
: y7 S& k! W0 ~- d, t4 a7 Ediscontinued TKI between 2003 and 2012. The total median follow up time
8 C I7 S* p$ x/ e9 qsince diagnosis was more than 120 months (mos) (range, 45 mos to 304
3 s: r" v8 K1 ]3 V# }mos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
" m3 N& r) L$ z" }: B) Nfemale. All pts had been diagnosed and treated in chronic phase., E) y9 n9 Y. G$ p
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI
/ s" O& Q6 K) ?% D7 das initial therapy (4 received imatinib 400mg/day, 10 imatinib
8 t5 w8 b0 b% }( b1 z/ h600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with
/ x# O! I, s3 LIFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN
4 q9 B7 d6 ], t5 E1 U' E9 w0 }+ Ifailure. Pts treated frontline with TKI started therapy within a median" A- W' K, p4 J" F5 L
of 0.8 mos from diagnosis (range 0 to 4) and those with previous7 s {( \3 V$ i+ l
interferon (n=11) after a median of 60 mos from diagnosis (31 to 164% l6 G7 l" n3 `8 Y$ c! y) x/ m
mos). Before TKI discontinuation 21pts (81%) were receiving their first
7 f% n: {( W# w/ R6 C- ]" ]) NTKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete
u6 b3 @% e# K/ T- _cytogenetic response (CCyR) had been achieved in all 26 pts at a median7 s. X" j4 }8 B; P+ G$ u/ H6 K( H
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of+ G4 e# R* T3 C" c! F2 F( A: ^( E
9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All! J* G: q1 D( h5 O6 M
patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)
) C x* G% I2 b( m1 shad undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
- z6 O& c T$ O, F8 mmedian duration of CMR before TKI cessation was 62 mos, (0- 118). The+ @, a4 ]( R+ f9 d% P8 {
median duration of total TKI therapy was 101 mos (3- 135).) n# F2 B7 X9 s3 s p& K: P8 I
6 d: h3 B6 q v0 s8 dFourteen pts (54%) discontinued TKI due to adverse events, 2 pts
0 J4 I& E0 K# C* L3 Ndiscontinued to become pregnant, 5 decided to stop after long CMR, and 5; I3 F4 Z4 G( Q0 z
pts discontinued for financial reasons. After TKI discontinuation
h2 I2 }& B$ t9 X6 V, Hpatients were followed for a median of 11 mos (5-131). Among pts with
/ x# H) A8 m" S0 n+ H5 j7 j" ^CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a, U* c8 O. ?' A
median of 4 mos (1-11) from discontinuation with median transcript level/ l6 k) @% X- D, G$ s9 v6 f& ]7 [
at relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF
: j2 M6 W; D7 R( S# N% Ntherapy had CMR at time of TKI discontinuation, 50% of them relapsed.
- ^: g3 Q3 \. z& D) b9 \Among 7 pts who discontinued therapy in MMR, after a median follow-up
4 P4 ]8 i* R9 Zfrom discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,2 C. I) F' _) p k) z# |+ D/ L
one has minor CyR and one CCyR without retreatment at last follow up
3 c( \ @0 B$ k' @- Gafter 78 and 105 months from TKI discontinuation, and one transformed to
" v/ x. _# U1 d& \9 faccelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
7 a4 C6 b8 a, K) z, @' S; E( W# [to MMR. Three pts had a transient molecular recurrence with spontaneous V: N2 r8 i4 n' O" ]- J
re-gain of CMR. Seven pts with relapse were treated again with TKI, 3
2 l1 _+ ^1 G: m2 mwith nilotinib, 2 with dasatinib, and one each with imatinib and1 X6 {. Q* E. V; c" _
bosutinib (the later in AP). After a median of 13 months on therapy9 c$ d: R [7 Y5 O
(range 4-52) all patients improved their response, 5 with CMR and 2 MMR: M @) t/ e4 G) W5 L/ o5 R
(including the pt that had transformed to AP). There were no deaths or
# E* c) R& k- xtransformations to blastic phase of CML. At last follow up 14 (54%) pts4 B. E# I& r) A3 S- v% V
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
; [" ^; J, Z: x/ B+ B& m: TPCyR.6 f/ T, [% h6 H. N1 |9 I
" w/ c9 v; g' ^& ]. UConclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular! {7 d" y! e( k$ D+ o; D/ o
relapse in nearly half of the pts who discontinue therapy in CMR. Some3 T3 l$ s' e" U! @4 |; O/ a. p
pts who discontinue in MMR may have sustained MMR. Treatment
Q8 x: N2 Y( r; c. Ddiscontinuation should be considered experimental and cannot be
' l, c4 K' p3 Z" R) R5 O4 Erecommended to pts as a standard approach.
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* a! B$ E, k) i- f, P. ]. J7 n1 A- `Disclosures: Ravandi: BMS: Honoraria, Research Funding. |