MDACC has, for the first time, given their experience of TKI
{" U l- D9 V% r# `. _" mdiscontinuation. The doctors at MDACC look at 26 patients who- S: k/ k. F; Y+ q
discontinued therapy from 2003-2012 for various reasons. These reasons
0 Z) k: e& p) g# L2 d/ Zinclude long time in CMR, adverse side-effects, pregnancy and financial
% s, p! b5 S1 a& H1 sconstraints. Please note that 17 patients discontinued therapy in CMR* e/ s/ o1 B+ F* [, t
and the rest in MMR. Of the patients in CMR who discontinued therapy,
7 ?" k2 \3 f; X5 A' a47% had molecular relapse. Those in CMR who discontinued and had taken2 n7 P7 O8 _2 a& x# R+ }" }1 M
prior Interferon to a TKI, 50% relapsed. Also note that of these 26
5 x$ \; x& S* D1 X. \/ B& apatients, most had been treated with high dose Gleevec.
& G6 w! E- J5 D: W3 V) J8 Q" R% h" w3 m5 \; R- F8 u
"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17. n: r1 _( O# \) l8 c* u
(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.
% D$ e% h( _$ q( WThe median duration of CMR before TKI cessation was 62 mos, (0- 118). l- n. m, q2 e( v% Z- p: q
The median duration of total TKI therapy was 101 mos (3- 135)."
# i' _4 r' p1 x
$ V! _! o% t) f: }4 pTherefore, the median time in CMR before discontinuation was about 5
5 r/ t: W$ l* G% ~years. The median follow-up is only 11 months. The median time for
1 j( f+ f) M% U/ E0 \1 @& M- t1 v; wmolecular relapse of 8 patients who had been in CMR was 4 months and7 q1 ]/ p" V, N4 I
they relapsed with median PCR value of 0.01 on the International Scale.
" n8 c7 `# e# [& L2 @: ?
+ I# Q' v3 y3 ^4 J: _0 iOf the 7 patients who discontinued when in MMR, 4 remained in MMR at a7 u$ Y5 p/ z: W5 k
median follow-up of 21 months, 1 remained in CCR, 1 in active disease ]) {2 V: ~5 J2 f* ~$ L
and 1 transformed to accelerated phase off drugs. Therefore, from this
, K4 b( | x$ H$ zdata, scarce as it is, there is a risk of transformation to advanced
* d1 ~7 [# ]3 J) }disease if one discontinues drugs in MMR.8 e+ I6 j1 u$ j3 |/ v
6 B' g7 d3 u* M B k3 z! Z s
2 patients were PCRU (4.5 log machine) and these patients relapsed0 z0 A" B' w1 w/ F% o8 y
into MMR when drugs were discontinued. W) B2 e: h+ X9 ]/ t
' k" W4 N* `6 W% _! [9 `: ^Seven pts with relapse were treated again with TKI, 3 with nilotinib,6 q4 S" W6 T, y4 N2 c% }/ A
2 with dasatinib, and one each with imatinib and bosutinib (the latter: u: F4 l+ j4 W2 A
in AP). After a median of 13 months on therapy (range 4-52) all patients
% G7 V" ^4 f& Y! p6 |% i& nimproved their response, 5 with CMR and 2 MMR (including the pt that had% N+ ~7 T$ v. b" k% Z
transformed to AP). They do not say why all patients were not retreated
& q7 S$ H1 M* g7 ?with imatinib and had to take Nilotinib and Dasatinib. Also, note that
9 ~2 Y' g. ?8 V. ~one did not regain CMR at the 13th month mark though it is good news
2 K6 s% N7 `8 d7 ~that 5 did. It may take some time to regain CMR for some who have gone8 \) R3 ]- ~/ ?+ c! H
off drugs and relapsed. However, from our own list experiences, some
A+ r) [' v/ |* Bhad regained CMR fast when they retook the TKI.8 j9 Y: ~: y* @/ @ e% t
8 r; ] y& Q& l
The doctors conclude that treatment discontinuation is experimental- a4 M8 }3 h& U; |; }8 I# V4 v
and cannot be recommended at this stage as a standard procedure.4 w; g; Y) M* h1 X
' t _4 l7 ]. A8 I9 i3 HBest Wishes,
" x6 R1 g$ c5 T- |" p2 t
( _9 [2 \* |' ~4 B: |2 uAnjana
" e" o( C! o; \8 x9 b; @
9 c9 \; \: _) @4 w: X: Z2 T% T7 r+ }3 i9 i9 Y( P
$ I% `# k+ S a+ N. @6 e- w! h$ P. d' Z" M: q* e
, l& |4 j* S5 H. [' U' T4 F2 H3 Y
" h0 V9 [9 Q. P+ Z, H" u m, L# Y/ e, ^& s# W% [
, c% ~ g; H; u1 Z+ h, D+ d; I# T( t$ D& v
% g V+ ^$ ]6 N& ]1 l3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor
: {9 j6 e9 ~+ Y& @& dTheray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single4 q. R" H' F1 Y! _7 Y
Institution Experience4 l% a% A' _% v5 O+ q
Program: Oral and Poster Abstracts2 @- Z( M0 {# E. I
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III: X/ b1 k- F$ g% v
/ x2 z9 O4 J$ b. \9 {- AMonday, December 10, 2012, 6:00 PM-8:00 PM$ `: ]) N& S" q' _% O
$ \' Y% \/ q0 V/ P. ^9 MHall B1-B2, Level 1, Building B (Georgia World Congress Center)$ _' v- w0 Q k7 V
6 A! R+ f( @* S yOhad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1," c; J: O- v2 R
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
& c) G9 k) N" @: sStefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,
# u$ E8 g( X+ r6 G q/ o6 dGautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.5 W0 A4 q `- p" H( a- C
Cortes, MD1
. o! w0 m) e# g2 a+ I
: f# X- f5 Z7 `- o1Department of Leukemia, The University of Texas MD Anderson Cancer
8 C. @- x @! h6 N( Y4 iCenter, Houston, TX- a& E* C0 ]- U) _% x
2Department of Leukemia, The University of Texas M.D. Anderson Cancer
, [5 ^1 j3 E9 i$ v% nCenter, Houston, TX. [ A8 ~5 O: p" i8 v
9 g/ w( ~% ]. y+ }$ I7 f
Introduction: Some recent studies have reported on the outcome of CML
' K2 W/ ^! l& \8 }! D5 kpts who discontinued thyrosin kinase inhibitors (TKI) after achieving' k5 m: r+ f! U0 p4 Z
sustained undetectable bcr-abl transcript level. Most patients who stop% W+ D' [4 V- y( u( p! ?! a1 L
TKI have experienced molecular relapse. Most patients respond after
6 c* n, N, q! X+ aresuming TKIs regaining undetectable bcr-abl transcript levels. These
6 P9 h" i# c$ ]. i7 i3 [series have prospectively planned treatment discontinuation and included
, [, i5 z7 U2 {! A) ]1 monly pts that have sustained complete molecular response (CMR) for at
; c3 C$ A! F, `least 2 yrs. However, in many instances pts may want to discontinue TKIs1 x1 }5 g3 i9 d5 @. a4 l
not in CMR. Various reasons may lead patients to discontinue TKI- r) @; o1 r) q4 d& d/ Z8 h/ S
treatment unexpectedly, among them severe adverse effects, pregnancy or
e2 c8 d: N, U. Heconomic constraints. This single institution experience reflects the: X0 d7 X+ h/ D# R% a2 k0 g* F
heterogeneous nature of pt-driven TKI discontinuation.
( S, Z. U/ y1 f* ?! Q- o% N3 |# U7 y/ v" f2 V) T. d
Aim: To characterize the outcome and profile of CML pts who chose to
+ Q+ P7 W- @8 J9 }6 Cdiscontinue TKI therapy in a single center regardless of their initial1 A9 e) {/ ^ ~; @' T$ S
response to TKI therapy.
/ S" X$ r( E6 r! B
* }- b! s6 P4 o4 ]: D. \Methods:We retrospectively analyzed MDACC data on all patients with CML6 `# _7 M- a0 e0 I1 c! P1 e# o
that were treated with TKIs in our institution and discontinued therapy.( v/ J, A. u2 K& a
; j2 [% g' U$ \$ k% a6 j$ BResults: A total of 26 patients with CML-CP managed at MDACC
! Q# E/ J3 w/ M0 B+ D! z) r% Ediscontinued TKI between 2003 and 2012. The total median follow up time
: ^! U6 B) S# Isince diagnosis was more than 120 months (mos) (range, 45 mos to 304
6 f+ m! A4 e4 |5 Tmos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
1 f- d7 | f6 m2 f7 kfemale. All pts had been diagnosed and treated in chronic phase.0 ?6 ~( u0 [7 O+ {. m
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI" D% R o6 H. z. H0 k! ?! D
as initial therapy (4 received imatinib 400mg/day, 10 imatinib
& t5 ]- G, c9 z l. P" o' \# f600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with3 n" P( _% l5 [& H- Q& [0 \+ o
IFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN3 g, U. O O9 m0 ?( ]
failure. Pts treated frontline with TKI started therapy within a median
. |2 U$ D; F' N% J3 yof 0.8 mos from diagnosis (range 0 to 4) and those with previous
) m' _. S% m2 e. \/ b- _interferon (n=11) after a median of 60 mos from diagnosis (31 to 1649 Y) z: Y$ Q5 D0 _
mos). Before TKI discontinuation 21pts (81%) were receiving their first
7 V0 a9 G1 L- R6 w _9 c5 |TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete
9 B( S- i1 q, @' F) _& [cytogenetic response (CCyR) had been achieved in all 26 pts at a median, S. }$ z7 @' u3 J; j
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of
# R5 w' b) a7 G* s% b2 S+ H& b- N9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All' o" j' S- d( T$ j) h& n/ a- O* c
patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)4 t; e! @" u _! k- X* e# S5 L
had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
9 v. z( W w) x. S+ {median duration of CMR before TKI cessation was 62 mos, (0- 118). The
; z3 n5 g t# I% rmedian duration of total TKI therapy was 101 mos (3- 135).! ~, S$ h1 s3 `8 T, y2 } y
* [$ N% c7 C- w K2 b* C8 s" R- mFourteen pts (54%) discontinued TKI due to adverse events, 2 pts
' E5 X3 Z' M" p8 S) W6 l6 B udiscontinued to become pregnant, 5 decided to stop after long CMR, and 5
' J( G9 I6 C1 ?+ y, Bpts discontinued for financial reasons. After TKI discontinuation
2 X4 \7 f/ r$ R2 D i9 kpatients were followed for a median of 11 mos (5-131). Among pts with
7 L% ~' b! Q+ l0 A' YCMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a
7 c$ o; S3 q+ Q3 Y) K4 Umedian of 4 mos (1-11) from discontinuation with median transcript level
/ @& g' c% ?1 S P! R3 P; ~3 J7 {at relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF
7 r. s$ ^" C$ `' i8 Otherapy had CMR at time of TKI discontinuation, 50% of them relapsed.6 ^8 o' V; G# i/ N' r4 ^2 V4 \( k
Among 7 pts who discontinued therapy in MMR, after a median follow-up) n; d* e. K$ q
from discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
C0 |6 k J0 D! l) y' Vone has minor CyR and one CCyR without retreatment at last follow up
C, G6 w; R3 G" v4 g- i- R+ r2 T2 Dafter 78 and 105 months from TKI discontinuation, and one transformed to. l5 d: _7 i- m& Q! s
accelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
! m/ X5 W6 j W3 \# Mto MMR. Three pts had a transient molecular recurrence with spontaneous
+ D# v6 P: [8 h2 ~4 [) {re-gain of CMR. Seven pts with relapse were treated again with TKI, 3
* k' d! \7 c0 A$ {with nilotinib, 2 with dasatinib, and one each with imatinib and+ D- E; j1 u. H2 h8 t
bosutinib (the later in AP). After a median of 13 months on therapy
0 P' G2 A0 l9 x2 B(range 4-52) all patients improved their response, 5 with CMR and 2 MMR
' S5 _) u3 X' ~: [(including the pt that had transformed to AP). There were no deaths or
! Q& V( k% [8 L: _9 D. Vtransformations to blastic phase of CML. At last follow up 14 (54%) pts/ x% U% c- D( ]/ d2 {; ^
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
2 Y0 ~9 e/ V$ E- `6 G+ QPCyR.
7 U9 H- X2 W; k* \& z
4 W! {& f7 Z! }8 y" h3 }; GConclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular& a: g. B" u) C
relapse in nearly half of the pts who discontinue therapy in CMR. Some* t( i6 e4 ]" p
pts who discontinue in MMR may have sustained MMR. Treatment( t2 D( [) i4 F i4 q5 u( X0 [
discontinuation should be considered experimental and cannot be
, `! k" @ \6 frecommended to pts as a standard approach.3 C- W1 a. b! a: d& P, v
/ K8 U$ m+ S) i: R
Disclosures: Ravandi: BMS: Honoraria, Research Funding. |