MDACC has, for the first time, given their experience of TKI
9 t! J/ X2 t! x9 ^2 x+ Gdiscontinuation. The doctors at MDACC look at 26 patients who& m$ M0 X/ F, j; x
discontinued therapy from 2003-2012 for various reasons. These reasons- m/ R5 q" p6 g! }" }/ Z M; F
include long time in CMR, adverse side-effects, pregnancy and financial
- y8 ]' z$ J, g, d. s. Hconstraints. Please note that 17 patients discontinued therapy in CMR' Q4 K* C! m+ u1 J1 ^! e& c2 G
and the rest in MMR. Of the patients in CMR who discontinued therapy,
( [7 O5 `/ D, Q/ {+ }3 s! e47% had molecular relapse. Those in CMR who discontinued and had taken. ^6 F$ J! ?$ S0 S, c X, v4 K
prior Interferon to a TKI, 50% relapsed. Also note that of these 26* z6 e$ S: m" a, v, Y9 P- l; `
patients, most had been treated with high dose Gleevec.
# q* m7 \& h! j' P5 |8 H3 Z3 l
8 @0 C; r5 k% b7 p"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17
1 s' C# f7 ?9 H c$ k/ z3 T(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.& s4 N9 r4 e7 i1 |6 T& ]
The median duration of CMR before TKI cessation was 62 mos, (0- 118).
( F+ r; G7 E! e2 X) M* XThe median duration of total TKI therapy was 101 mos (3- 135)."* p2 R h S) G6 T: H5 u, n
9 J. \, v$ D1 T! I& F9 a5 h
Therefore, the median time in CMR before discontinuation was about 5
# p; F, ]1 }+ r/ [4 jyears. The median follow-up is only 11 months. The median time for
' N# |6 C% g& m; S+ z/ tmolecular relapse of 8 patients who had been in CMR was 4 months and
1 k* a- t& H. Q7 E0 e7 ~they relapsed with median PCR value of 0.01 on the International Scale.
M3 I3 A( r: U b
; u0 s( O/ R1 z I' g" g4 z; t% F1 AOf the 7 patients who discontinued when in MMR, 4 remained in MMR at a
8 l+ l& a7 q; Z* Y0 Y# Umedian follow-up of 21 months, 1 remained in CCR, 1 in active disease* q9 e; T D' T4 Q3 r) Z
and 1 transformed to accelerated phase off drugs. Therefore, from this; f- Q1 ], p3 M# p
data, scarce as it is, there is a risk of transformation to advanced
! y& b# ^! J; p, h8 r+ ~2 jdisease if one discontinues drugs in MMR.
4 s" [- _* E4 U. l# O5 o
! s: @. l) }. }6 P2 patients were PCRU (4.5 log machine) and these patients relapsed4 d8 o8 A9 `% j- Z$ f8 ] j% w
into MMR when drugs were discontinued.0 n5 B( ~- [ b
! q- x+ I" ]* G6 h: ]$ M6 ^Seven pts with relapse were treated again with TKI, 3 with nilotinib,& ^6 \8 m# [* [8 [* \6 l4 S
2 with dasatinib, and one each with imatinib and bosutinib (the latter5 [4 V0 {# H2 T* g% _
in AP). After a median of 13 months on therapy (range 4-52) all patients5 a$ f8 Q5 ]4 G3 S
improved their response, 5 with CMR and 2 MMR (including the pt that had
6 \1 S& \8 o: V/ M9 U, e! etransformed to AP). They do not say why all patients were not retreated5 {. I& {& |( \/ ~0 t( g) @
with imatinib and had to take Nilotinib and Dasatinib. Also, note that( L+ S5 q4 H/ [ V% s ?9 K% s
one did not regain CMR at the 13th month mark though it is good news$ P2 c9 {5 N( W3 ]8 N. H3 e
that 5 did. It may take some time to regain CMR for some who have gone3 Z1 \) J d @8 h+ k h
off drugs and relapsed. However, from our own list experiences, some
# l9 u: I1 ?6 R6 y3 e3 ^had regained CMR fast when they retook the TKI.& z# ]) G. i9 b+ U0 l
! O, C5 Y" \: D' ~
The doctors conclude that treatment discontinuation is experimental
: E- R6 S5 ^4 c: |; q e) z8 tand cannot be recommended at this stage as a standard procedure./ y3 \1 G7 Q' e2 [) J; c) o
4 U5 _; G/ K) b( O* [3 D2 X; z/ ^* M
Best Wishes,
& x" a" }( `/ P) k5 f1 C
/ B$ x3 d! Q- P2 o) wAnjana1 D& N' a, c; f/ {% J
8 J9 A7 {# ~; j- F: H7 G* x. d4 P4 u
# D" |3 | Y$ D3 D$ g2 Z+ z
( a5 D8 }& V9 m6 [
+ v7 _3 _; V. u4 y) {2 V# c o
* B# c6 z R) P9 q: l; I2 Z' |* e. E, b" S4 I3 G: o- @. j
3 \4 Q- U; Q" o$ ^
: O; Y U: _7 R0 D1 R Z3 L8 w) U. Q' |. S! X
3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor
* p8 ?) Y- n" ]8 g' n s: U; c' LTheray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single
; {$ u2 i4 j: F- h( \, K+ p zInstitution Experience1 w9 E: C/ c" W; f0 k
Program: Oral and Poster Abstracts, C5 l1 X& Q* N3 T, E7 s4 }
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III
% N! |4 J0 v$ D; F1 }
9 q; s' c+ P, w# R3 LMonday, December 10, 2012, 6:00 PM-8:00 PM2 S: n+ d9 U% P+ \* m2 `
! M& W* i* W5 c; e* i7 j
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)& k7 r1 A7 V, ^5 c% _3 V$ _
& y$ L' k: V( o$ P3 Y# m
Ohad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1," x! P/ C9 A' H3 r
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
0 e$ `% `) u0 Y) D$ l+ y3 NStefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,, L7 K8 g( m( _
Gautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.- ~8 v" d* \+ S. Q
Cortes, MD1
$ W$ L7 f/ l, L; a; j- [& r: A4 y! J
1Department of Leukemia, The University of Texas MD Anderson Cancer2 }+ p$ ]+ U8 n# u3 \
Center, Houston, TX
1 q- ?3 X: E3 o( b- u% ^2Department of Leukemia, The University of Texas M.D. Anderson Cancer
. }4 i! X$ F A/ T' O# JCenter, Houston, TX$ S1 y( b9 m: K4 A
9 S( s1 O- c: m$ I" P6 K3 }
Introduction: Some recent studies have reported on the outcome of CML: |6 v5 |3 H. D7 R$ R
pts who discontinued thyrosin kinase inhibitors (TKI) after achieving
! f5 ]; S) {$ x* u. z# T7 }' {7 qsustained undetectable bcr-abl transcript level. Most patients who stop# n1 B/ q. v9 w. P1 a6 E/ n1 x/ B) Z! u
TKI have experienced molecular relapse. Most patients respond after
( P/ S6 O: V- F6 X! x! f2 m+ Zresuming TKIs regaining undetectable bcr-abl transcript levels. These
E, ^7 K! `8 T* ~) Aseries have prospectively planned treatment discontinuation and included' u- @, L \- P# n- Y7 i# k
only pts that have sustained complete molecular response (CMR) for at! n7 R" }$ |9 V* e
least 2 yrs. However, in many instances pts may want to discontinue TKIs
f8 C" i" p- n9 tnot in CMR. Various reasons may lead patients to discontinue TKI* l5 d. H1 G' a# O i# g$ ?
treatment unexpectedly, among them severe adverse effects, pregnancy or. \5 ~; h' e/ q+ |$ w
economic constraints. This single institution experience reflects the' \- j( ]0 L+ E( `
heterogeneous nature of pt-driven TKI discontinuation.5 X, N ?5 M$ t+ r. r& I
+ X: q1 y3 i! y6 _
Aim: To characterize the outcome and profile of CML pts who chose to; U. o! Z4 E% x2 n
discontinue TKI therapy in a single center regardless of their initial) J2 X( ?$ S/ c- R
response to TKI therapy.
4 _0 b* V" A% m K: ^5 f4 J8 v) Y" B( t4 w
Methods:We retrospectively analyzed MDACC data on all patients with CML- ?! L- P+ B$ B. J; X/ \% Y1 R
that were treated with TKIs in our institution and discontinued therapy.
5 _/ A( ~& N. M" d* o( K
* i& o" j# T0 ^0 K# b* v- NResults: A total of 26 patients with CML-CP managed at MDACC
: a8 f' F" @* `1 ^9 hdiscontinued TKI between 2003 and 2012. The total median follow up time
) O' x# [! }! L+ j" ^: I Jsince diagnosis was more than 120 months (mos) (range, 45 mos to 304( m9 Z8 f& ~: q7 [& Q3 J0 r; m
mos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
. x. x4 ^5 o' v* c: E1 Dfemale. All pts had been diagnosed and treated in chronic phase.
8 z8 l+ t( r0 Y' EInterferon was initial therapy in 11 pts (42%) and 15 pts received TKI0 O: K# l* y, d+ W
as initial therapy (4 received imatinib 400mg/day, 10 imatinib
( y0 A- ^) w/ `6 a600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with
+ B0 D# v1 a+ |( w2 w. C6 jIFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN
2 | }+ V3 _" E: k. n+ R* N( a7 rfailure. Pts treated frontline with TKI started therapy within a median
8 m, A g7 A, k) }. F+ |# D& `of 0.8 mos from diagnosis (range 0 to 4) and those with previous
, E/ b/ d# T+ ninterferon (n=11) after a median of 60 mos from diagnosis (31 to 164
. h& v5 c i) ?9 b9 Imos). Before TKI discontinuation 21pts (81%) were receiving their first( j; A( W' ]9 {( ^+ n
TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete
. J d, {6 u7 i0 ccytogenetic response (CCyR) had been achieved in all 26 pts at a median9 n0 i9 T' H: m \3 T( S4 X
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of
2 h8 |' r; R0 D7 i3 P+ ~9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All
) p9 E+ w1 u% S1 ~0 b) J9 @patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)
* X. r% h2 z1 p/ c8 @9 vhad undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The( T ~( y9 @2 S- a
median duration of CMR before TKI cessation was 62 mos, (0- 118). The* h7 v I6 j7 M7 d
median duration of total TKI therapy was 101 mos (3- 135).
( I4 }8 h% e* K9 e
3 |8 t: [! M( Z! MFourteen pts (54%) discontinued TKI due to adverse events, 2 pts
; a- P2 h7 l/ E) u, ddiscontinued to become pregnant, 5 decided to stop after long CMR, and 5- |1 h3 e4 {2 n1 w. u
pts discontinued for financial reasons. After TKI discontinuation5 n4 I" R, X8 @ I
patients were followed for a median of 11 mos (5-131). Among pts with
1 K# D+ Q4 _% Q, ?7 xCMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a
7 S" |6 {$ B6 g- S6 wmedian of 4 mos (1-11) from discontinuation with median transcript level# m1 e- q1 ~& r
at relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF" ^$ I; g$ ^8 i
therapy had CMR at time of TKI discontinuation, 50% of them relapsed.
8 Q* h) [+ B( F/ I7 ZAmong 7 pts who discontinued therapy in MMR, after a median follow-up: B4 j% q2 c* m
from discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
- u3 L2 G& |# S9 B6 d' E9 \, xone has minor CyR and one CCyR without retreatment at last follow up0 ^: i. _; E2 ?# x$ p- l1 C
after 78 and 105 months from TKI discontinuation, and one transformed to9 ^* Z9 X& x B% R5 W
accelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
( t% m# u' h6 i7 f8 ~- _6 `( j! {to MMR. Three pts had a transient molecular recurrence with spontaneous8 Q/ l" L2 q1 Z3 A. I
re-gain of CMR. Seven pts with relapse were treated again with TKI, 38 u# z2 p$ H$ h
with nilotinib, 2 with dasatinib, and one each with imatinib and9 p5 F; D2 ~$ X8 c! t' q
bosutinib (the later in AP). After a median of 13 months on therapy
* A- O5 v8 k' w/ b2 r7 n8 e(range 4-52) all patients improved their response, 5 with CMR and 2 MMR+ k) [% v; x8 E1 v' h) y) q
(including the pt that had transformed to AP). There were no deaths or
6 p0 l: I6 r' I# _6 N" g2 qtransformations to blastic phase of CML. At last follow up 14 (54%) pts1 g1 L- [! p$ l' K2 K! S. p1 t" f; Q
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
& k0 }: k$ w: \$ s& N8 ?# @7 oPCyR.
% y; l0 U9 Q3 r2 t: |7 M9 C7 z0 Y# W x& h+ M. Q0 F! e
Conclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular r( M E8 Z5 D5 k/ z4 E* t5 a
relapse in nearly half of the pts who discontinue therapy in CMR. Some1 W1 Z8 G3 g1 H
pts who discontinue in MMR may have sustained MMR. Treatment5 e1 O& u0 M( u- [* [
discontinuation should be considered experimental and cannot be# u# h8 t2 A5 p( f$ G8 i& e4 |0 w' }
recommended to pts as a standard approach., }! S- Y5 g2 S- k7 c
% C2 b9 P0 t! Y; d3 x6 MDisclosures: Ravandi: BMS: Honoraria, Research Funding. |