MDACC has, for the first time, given their experience of TKI
$ u7 \$ {9 |+ a# c8 d* cdiscontinuation. The doctors at MDACC look at 26 patients who
- u9 `7 N8 p; N, S/ H. `. Vdiscontinued therapy from 2003-2012 for various reasons. These reasons M7 @- i; c! G$ o; q7 Z& m
include long time in CMR, adverse side-effects, pregnancy and financial
& L# T# p. R+ E& I0 G& sconstraints. Please note that 17 patients discontinued therapy in CMR$ u8 d3 S) c) N3 W
and the rest in MMR. Of the patients in CMR who discontinued therapy,
4 _- P' ~% }0 C5 [: L- v- W6 o% F) Q47% had molecular relapse. Those in CMR who discontinued and had taken% V4 `% W1 z- E1 U Z2 ^
prior Interferon to a TKI, 50% relapsed. Also note that of these 26! m$ C9 x3 `" W- c' v6 ]
patients, most had been treated with high dose Gleevec.
- S1 O& b7 P7 v# @( }0 F) ~; Q2 _: K- s: l5 O3 k
"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17
. f6 a' }% `; w2 W1 H. l(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.
6 F* M4 r7 ?3 {$ Y9 R: k1 HThe median duration of CMR before TKI cessation was 62 mos, (0- 118).( @+ T: Y" c7 I$ }! `
The median duration of total TKI therapy was 101 mos (3- 135)."4 s9 W5 s. k& W+ v! r" w
, g* }5 P9 x0 {. V; iTherefore, the median time in CMR before discontinuation was about 5
- P0 s9 M- r, q0 Uyears. The median follow-up is only 11 months. The median time for
$ C) H) d$ U# s6 S2 h- H. L$ E2 Omolecular relapse of 8 patients who had been in CMR was 4 months and2 M0 _2 i8 O. Z( Z
they relapsed with median PCR value of 0.01 on the International Scale.2 Z- H% h. C5 D. l# j1 {, N7 {
$ j) \2 V& _' ^6 p! S' i e
Of the 7 patients who discontinued when in MMR, 4 remained in MMR at a
4 X0 c% c0 [5 Y2 L: hmedian follow-up of 21 months, 1 remained in CCR, 1 in active disease( ]- J5 _4 O# @, d' \
and 1 transformed to accelerated phase off drugs. Therefore, from this
! t+ F, T# o+ a& z; i/ Vdata, scarce as it is, there is a risk of transformation to advanced! ?9 r8 W; k9 V! K" @2 O3 i& H4 l
disease if one discontinues drugs in MMR.
% x2 W: U6 y! Z: a7 _# g+ Y
0 b0 I9 v0 F4 q2 patients were PCRU (4.5 log machine) and these patients relapsed
# v! h4 ~0 ^! C0 X. |1 Vinto MMR when drugs were discontinued.4 `9 N: J- `0 ~
% I8 z. {# k2 a5 J' o) E+ l% ]" iSeven pts with relapse were treated again with TKI, 3 with nilotinib,8 _* H/ G" `! s' X; `* y! I0 z# k; D
2 with dasatinib, and one each with imatinib and bosutinib (the latter
% v+ t, x& b0 \7 Jin AP). After a median of 13 months on therapy (range 4-52) all patients
4 w1 ?) p8 h7 [7 Kimproved their response, 5 with CMR and 2 MMR (including the pt that had# ^) `1 ^4 K( v2 b
transformed to AP). They do not say why all patients were not retreated- g+ W' E0 x- @* ~& m5 a
with imatinib and had to take Nilotinib and Dasatinib. Also, note that
4 S+ O) M Y: i& S- }3 Y- Cone did not regain CMR at the 13th month mark though it is good news7 p1 w+ C! w6 x7 y4 n. P
that 5 did. It may take some time to regain CMR for some who have gone0 U( f' m/ `0 C4 U4 h) L2 Z4 K
off drugs and relapsed. However, from our own list experiences, some+ N/ w9 T0 i. W1 }/ A
had regained CMR fast when they retook the TKI.4 Y/ v+ j8 ^! p% L
8 j+ S, m B6 ?( Y+ Q# S0 m
The doctors conclude that treatment discontinuation is experimental
7 t3 {6 s. y/ Q: y7 H" F0 `8 land cannot be recommended at this stage as a standard procedure.
4 U0 I0 h8 K* R4 T' T- W* v$ m
Best Wishes,3 {8 S' l! l1 m: ^2 W3 f
* J3 v4 y6 V0 [2 A5 j- a
Anjana$ Y; ~; {6 n5 ?0 y" d; h
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H1 n) d/ S3 G4 a# U& U$ s! v
( i/ E/ A1 Z. d0 {9 n! v& ?# b$ v; f$ p/ _, [9 {9 i3 q
& J; Q4 q* P3 I! M, Y. g( G! c: b1 _5 z- l! @# u. a
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3 f' u: Z6 Y# K7 {5 j2 M8 {$ `" Z6 }* _/ q' g* v3 f
/ K& {% f6 k! m- ^8 I+ }% ~
3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor+ f# y4 ?! J: w' G) R! @9 E
Theray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single0 b% V4 I" }6 O/ k
Institution Experience
/ \+ B( r: o" ?Program: Oral and Poster Abstracts2 @+ P/ I+ V' C5 k) G3 n& z3 f' z
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III
5 f: _2 _% u9 A+ a; l1 s5 n
& H, I/ C9 a6 i4 XMonday, December 10, 2012, 6:00 PM-8:00 PM7 l* J5 G3 L1 h5 L
/ p1 u0 x/ D1 v, t% n. E) j
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)
% ]4 _/ r* P3 n" d' E- f
9 ], c( n) K% f/ O! h, _ \Ohad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,
: w0 [9 i" B0 L7 J) | k! DElias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,8 A# |% U" n; |1 v
Stefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,& h* v! m; G1 l( f% I1 \ g8 y2 n) R
Gautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.9 ?) ?1 s$ f W( k; H
Cortes, MD1
! A9 W: s$ Y0 ^, S
: c! h0 r; u! _1Department of Leukemia, The University of Texas MD Anderson Cancer
+ j7 z: \' c/ Z: e; s2 vCenter, Houston, TX+ i8 m; e8 w; R/ n i7 M
2Department of Leukemia, The University of Texas M.D. Anderson Cancer
" S" d' Y% b( W+ Z# T1 yCenter, Houston, TX
& G o( l' A& _7 i0 z0 |* `5 e5 E* }7 |( b% J
Introduction: Some recent studies have reported on the outcome of CML
7 B' }& `. [6 I# C' y Jpts who discontinued thyrosin kinase inhibitors (TKI) after achieving- x( w8 ~- U' W3 K/ H+ n
sustained undetectable bcr-abl transcript level. Most patients who stop
: R1 E! o1 c1 {( b5 \& K, i5 qTKI have experienced molecular relapse. Most patients respond after- K- F: v# x- ~' q
resuming TKIs regaining undetectable bcr-abl transcript levels. These% [- j6 W) j* n0 R. Q
series have prospectively planned treatment discontinuation and included* n' {6 e' `' j
only pts that have sustained complete molecular response (CMR) for at
% b3 J( t0 D4 y# E) W; _( R! L% |least 2 yrs. However, in many instances pts may want to discontinue TKIs) Y* F9 V* |* X4 N* m5 ~& R
not in CMR. Various reasons may lead patients to discontinue TKI
7 Z* M, f8 O+ H7 N' Otreatment unexpectedly, among them severe adverse effects, pregnancy or) ]# x' R: l. _( Q: f j, H
economic constraints. This single institution experience reflects the# k4 ?0 z1 G' z5 }, o
heterogeneous nature of pt-driven TKI discontinuation.- \& b n& j2 V- d G
5 d' [# T( |# s9 U# g3 n" Q
Aim: To characterize the outcome and profile of CML pts who chose to
% \7 L2 c! M2 A. \5 o. Odiscontinue TKI therapy in a single center regardless of their initial
+ ` \ T h0 n- y3 f8 J6 I! Vresponse to TKI therapy.5 v7 j) J5 h9 D& m
. J" d# }( k& F! E$ F lMethods:We retrospectively analyzed MDACC data on all patients with CML( D/ A# w+ F8 X
that were treated with TKIs in our institution and discontinued therapy.: e! B; X( c' ~* I
( S5 T8 V9 F8 P* Y
Results: A total of 26 patients with CML-CP managed at MDACC
2 a# ]) V4 [! \8 Z$ T8 pdiscontinued TKI between 2003 and 2012. The total median follow up time
/ O3 @; }0 r# P* R0 h! t4 y: bsince diagnosis was more than 120 months (mos) (range, 45 mos to 304
3 D& x @. ?. V2 |/ F! Kmos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were$ g; F4 ?: V* Z. \% E
female. All pts had been diagnosed and treated in chronic phase.
{# ~5 y6 s6 n x; ^2 e6 m9 }Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI. l& a, a% T6 w1 E
as initial therapy (4 received imatinib 400mg/day, 10 imatinib. B& e& l7 q0 n8 H) t d Q
600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with
: r( B, ?2 u; o" U, r" L* r5 \IFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN
5 ?/ f0 r! q% V5 b- S4 `failure. Pts treated frontline with TKI started therapy within a median3 j3 \ b8 C+ \, u9 S- B- T( Q9 x
of 0.8 mos from diagnosis (range 0 to 4) and those with previous
, r5 \: y- w7 \# `interferon (n=11) after a median of 60 mos from diagnosis (31 to 164- h. Z$ g5 E- l) C$ v" a0 P
mos). Before TKI discontinuation 21pts (81%) were receiving their first5 `- B6 W5 x2 N7 K5 M5 J
TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete7 W, e, t1 _8 F" s) ~
cytogenetic response (CCyR) had been achieved in all 26 pts at a median t; |& \9 G. t; K- a8 l+ q+ i
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of
" S2 R0 f6 ~- R: w) ~# C9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All7 G: N; ]8 v/ c, t
patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)7 b7 a. E7 A, [* w8 L2 O& m& X7 |
had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
; t9 i: w' Y3 N: qmedian duration of CMR before TKI cessation was 62 mos, (0- 118). The9 n$ q) c( m: S q, G0 W; J3 D3 f
median duration of total TKI therapy was 101 mos (3- 135).
5 X8 \4 P" k* r& p" \9 u$ e) D$ h: X3 C' U- k
Fourteen pts (54%) discontinued TKI due to adverse events, 2 pts0 g) P$ N% ~# A% W
discontinued to become pregnant, 5 decided to stop after long CMR, and 5) c3 I0 @+ o8 p. W0 \: I# h
pts discontinued for financial reasons. After TKI discontinuation
, C# [+ L0 R1 h8 [patients were followed for a median of 11 mos (5-131). Among pts with0 \% V' N7 b, H! Q" _3 H z& z
CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a
2 ]5 i% J3 [+ z7 W# X) Wmedian of 4 mos (1-11) from discontinuation with median transcript level
; X+ _7 g( O2 ]+ ~1 e+ o, ?at relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF
8 S$ X3 K$ x. e* x Btherapy had CMR at time of TKI discontinuation, 50% of them relapsed.4 K) K; H: o" S6 ?
Among 7 pts who discontinued therapy in MMR, after a median follow-up) U7 k, N6 o& S7 ]! L
from discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
1 y( i A2 {8 Aone has minor CyR and one CCyR without retreatment at last follow up
: ` V" v( L. o& o+ W ~- {after 78 and 105 months from TKI discontinuation, and one transformed to
0 R) q1 W! _- y: \. h" }0 ~6 P/ waccelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed, S) s6 U# j# u" j7 n8 x/ d! g
to MMR. Three pts had a transient molecular recurrence with spontaneous4 z5 J( H8 @% f4 H
re-gain of CMR. Seven pts with relapse were treated again with TKI, 3
6 E/ K$ w# d; W% ?) f9 v5 vwith nilotinib, 2 with dasatinib, and one each with imatinib and. r- c1 ?: I9 q2 `! ?/ d; U& I
bosutinib (the later in AP). After a median of 13 months on therapy
* r- }* V3 M- k# x( Y# v- {& r(range 4-52) all patients improved their response, 5 with CMR and 2 MMR
: i) O1 I$ g; [6 ^(including the pt that had transformed to AP). There were no deaths or
8 m& E6 {4 z# n1 }0 P) f' Btransformations to blastic phase of CML. At last follow up 14 (54%) pts- k+ h1 v. B F. t7 m
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and2 \( L0 ^. {# o5 E0 R+ `/ S" q, @
PCyR.
2 O% c" [2 o2 W1 s: ?7 L+ m0 V$ r
. n* ^$ d( F# \4 ZConclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular
. W4 o- M# ~; S. g: d* S% Qrelapse in nearly half of the pts who discontinue therapy in CMR. Some' S- @2 t8 t" ? c+ a; [/ n' y8 R
pts who discontinue in MMR may have sustained MMR. Treatment9 A+ H M7 v/ ~$ M) b
discontinuation should be considered experimental and cannot be( K: y* M7 Z* l. n' X! U
recommended to pts as a standard approach.
! ~. \, T4 W; U; |2 Q, \& M" Q4 G
4 L2 d9 x( m1 J1 ]6 V# o2 i: f% nDisclosures: Ravandi: BMS: Honoraria, Research Funding. |