MDACC has, for the first time, given their experience of TKI
: j$ R% e& {& B5 H" k M9 R4 wdiscontinuation. The doctors at MDACC look at 26 patients who4 H k# y/ D/ G( }
discontinued therapy from 2003-2012 for various reasons. These reasons) m1 L& h/ y$ A5 j
include long time in CMR, adverse side-effects, pregnancy and financial
" T; X+ v1 L& m1 J: dconstraints. Please note that 17 patients discontinued therapy in CMR
( |) |( u! p: N. o2 Zand the rest in MMR. Of the patients in CMR who discontinued therapy,
4 ^% Q* B1 U& G; x& f/ x& t3 K& o47% had molecular relapse. Those in CMR who discontinued and had taken
' |, o# M9 X" f6 `1 f/ O) \prior Interferon to a TKI, 50% relapsed. Also note that of these 26
& f0 m# ~) Q6 f4 T& {; V5 kpatients, most had been treated with high dose Gleevec.4 o. l T" }9 |/ w: P n
2 C4 i0 f( l2 O; l+ Y
"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17
: j* E$ m0 ~, Y& P7 J9 p(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.
' O# c3 y/ s9 g' S4 X4 z9 vThe median duration of CMR before TKI cessation was 62 mos, (0- 118).7 L! b% F5 z/ V1 G$ d
The median duration of total TKI therapy was 101 mos (3- 135)."7 m. y- A# O: k
! w8 V1 R& x2 g2 v0 ]" z- J" ]Therefore, the median time in CMR before discontinuation was about 5
) |& O& n4 j- F' R6 u) T8 S5 A( uyears. The median follow-up is only 11 months. The median time for
7 B# @9 @9 w$ L3 F: Y. f2 C4 @0 _7 Omolecular relapse of 8 patients who had been in CMR was 4 months and! E. I( y( ]7 ^: f8 f
they relapsed with median PCR value of 0.01 on the International Scale.0 V* |/ d. X- t: X4 I6 f- e2 F
, E, i C! z6 y8 Z
Of the 7 patients who discontinued when in MMR, 4 remained in MMR at a
, |" d0 f# I6 K" k6 R9 gmedian follow-up of 21 months, 1 remained in CCR, 1 in active disease
; }3 e4 ]7 r, x' n2 F# Hand 1 transformed to accelerated phase off drugs. Therefore, from this
8 @) C7 n3 O0 Ydata, scarce as it is, there is a risk of transformation to advanced
; F5 P9 I' y9 z2 Ndisease if one discontinues drugs in MMR.: @6 @3 F9 J* z+ |8 h h0 S
( S8 X" V9 h9 I# c& N4 N2 patients were PCRU (4.5 log machine) and these patients relapsed; u y m7 t6 M3 C$ A) _! a g
into MMR when drugs were discontinued.
. M8 m f3 j7 p" Y+ n$ F) W% T. G: d i1 o
Seven pts with relapse were treated again with TKI, 3 with nilotinib,
6 O8 M# [* a+ ^' c+ r- V2 with dasatinib, and one each with imatinib and bosutinib (the latter
. s; H6 S' A& p9 kin AP). After a median of 13 months on therapy (range 4-52) all patients
3 W+ h" ?* K' O9 j3 O" I# v' dimproved their response, 5 with CMR and 2 MMR (including the pt that had# e. `* I' u" t9 |" t' f! G
transformed to AP). They do not say why all patients were not retreated
! `2 `: e0 F5 w4 A9 W( Zwith imatinib and had to take Nilotinib and Dasatinib. Also, note that
9 V! O* S& B; u0 I$ {4 @- Vone did not regain CMR at the 13th month mark though it is good news
! Y: w# L! h! C- J9 ^5 lthat 5 did. It may take some time to regain CMR for some who have gone
6 H o$ C4 U6 T. Eoff drugs and relapsed. However, from our own list experiences, some( c- Y3 g/ d# G \3 u8 ^1 S5 k
had regained CMR fast when they retook the TKI./ T* n+ _3 I3 l) Z
4 O; B; l' m3 z+ G% D' z" [* u* I6 |The doctors conclude that treatment discontinuation is experimental
D9 w' ^$ `) R& y/ C7 Z2 X5 U0 }and cannot be recommended at this stage as a standard procedure.4 }( M6 G" H: K' c
1 k7 g1 C! I2 p# PBest Wishes,7 F' Z: {3 K$ s" E- A$ ^% q7 T
/ u, c$ s g4 Q Y8 F5 r. pAnjana
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k1 p6 K$ F$ F( R
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' h B/ b8 H/ i1 n: J* r/ F
3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor# }5 g( b4 B2 S9 }4 {
Theray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single3 s/ H, `: [- ]" L! E+ D2 {
Institution Experience0 I9 ~7 U% G8 O9 @
Program: Oral and Poster Abstracts$ }, M2 `9 R7 z: R: {# j
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III( ]* ?2 f7 T; D6 C2 \* V, ]$ O1 m
; E1 G+ q( w) n# [. f
Monday, December 10, 2012, 6:00 PM-8:00 PM# |- ?& e n. T( m+ T# I5 u
2 w# R" J+ U+ h6 N _$ \! z1 C, Q
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)5 R, o& S% ^6 N2 v9 A
( A: j- l& ] X/ Y5 XOhad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,) V- g6 n3 C; K$ y+ v
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
9 d0 g! g1 g* ]Stefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1," e/ m8 f8 I8 \) n
Gautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.+ M' L4 Y) z J" p7 X' c
Cortes, MD1" {/ E" [3 j% ^8 w% Y$ E
4 J: \8 c* d _1Department of Leukemia, The University of Texas MD Anderson Cancer+ E; J9 N5 H& A. h
Center, Houston, TX
0 K) L i8 s* a2Department of Leukemia, The University of Texas M.D. Anderson Cancer4 U- ~* x1 x* \9 d- e t [/ k/ \( H
Center, Houston, TX% s9 Y) _8 M7 B5 x7 J/ R ^
; l' u! J* v5 ?* z- x: kIntroduction: Some recent studies have reported on the outcome of CML8 f: C. P7 p0 f. G* C
pts who discontinued thyrosin kinase inhibitors (TKI) after achieving
3 }% m0 l0 [1 m) p7 n: P3 b( usustained undetectable bcr-abl transcript level. Most patients who stop) t! e2 Z5 t1 K7 K8 h+ g# x; {
TKI have experienced molecular relapse. Most patients respond after: s6 a, A6 m4 j5 Z8 i
resuming TKIs regaining undetectable bcr-abl transcript levels. These
& C8 R) K K$ L |0 }. qseries have prospectively planned treatment discontinuation and included
3 E3 \( l& E9 zonly pts that have sustained complete molecular response (CMR) for at
" H, d! ~" @1 e. D; t3 _0 e6 Xleast 2 yrs. However, in many instances pts may want to discontinue TKIs3 U' {& e2 k; x7 M
not in CMR. Various reasons may lead patients to discontinue TKI9 l9 j1 F: O5 E' L* m* Z2 E
treatment unexpectedly, among them severe adverse effects, pregnancy or
; F3 t5 c+ m$ w3 w( Veconomic constraints. This single institution experience reflects the* `: x7 e, u8 Y2 N& I! J! A2 J. o
heterogeneous nature of pt-driven TKI discontinuation.
% _+ G) Z6 Y5 w3 ^3 k! z: I
! V/ w+ Y2 o8 }) @Aim: To characterize the outcome and profile of CML pts who chose to( \5 e, t4 v( @: V( U/ S8 g
discontinue TKI therapy in a single center regardless of their initial/ c& T) A1 _. e/ P4 ^* u U; M; S' ]
response to TKI therapy.
1 b% j2 h, g" g% G
! {( ~* U% B: @" \Methods:We retrospectively analyzed MDACC data on all patients with CML
' g9 [# M H( Y: J! A/ `1 Fthat were treated with TKIs in our institution and discontinued therapy.3 G% X* H: Z# G' i% C5 ?) B
Y4 d" h' e; |2 m( PResults: A total of 26 patients with CML-CP managed at MDACC
: N; ^; a/ J0 Y) y( ^# Idiscontinued TKI between 2003 and 2012. The total median follow up time
9 T0 T' c9 Y7 R; w5 msince diagnosis was more than 120 months (mos) (range, 45 mos to 304
# a; z. m' Z0 @$ e9 V# W$ Mmos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
& ]1 Q0 q! A5 H& }5 }+ ~- pfemale. All pts had been diagnosed and treated in chronic phase.
( p" s( f" L! n( g) @5 eInterferon was initial therapy in 11 pts (42%) and 15 pts received TKI
H3 t; y1 r b5 c _ F' f+ z3 `- ras initial therapy (4 received imatinib 400mg/day, 10 imatinib. y5 Q- a" c% F( o y& Z
600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with
" C+ }& y! {1 @5 _7 B3 V. uIFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN8 }1 ]; ^9 N9 c! H. ]- B
failure. Pts treated frontline with TKI started therapy within a median+ K- L2 D, [0 `3 L
of 0.8 mos from diagnosis (range 0 to 4) and those with previous7 w' s6 G- I" W3 q
interferon (n=11) after a median of 60 mos from diagnosis (31 to 164
. q$ u1 E$ f0 v1 Ymos). Before TKI discontinuation 21pts (81%) were receiving their first
8 ]( R J- u; T* c* D( N. S; `TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete) Q9 d) u& C0 ^" I8 M& n. h8 L, K
cytogenetic response (CCyR) had been achieved in all 26 pts at a median3 o; d6 {+ ?" ?- ^0 y1 ]
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of+ X/ D* _6 y% c# c
9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All
! e$ G0 Z2 m5 l% |' Bpatients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)
0 m' L- k) x8 thad undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
% `& x; V$ N4 n0 q2 w$ w7 F2 Jmedian duration of CMR before TKI cessation was 62 mos, (0- 118). The; L& l5 `4 @/ N6 ^
median duration of total TKI therapy was 101 mos (3- 135).
3 j/ `; R! |0 v6 E/ M
, E' J9 i* A0 KFourteen pts (54%) discontinued TKI due to adverse events, 2 pts
9 ]6 }$ Y4 y, i% y% d0 Q9 Vdiscontinued to become pregnant, 5 decided to stop after long CMR, and 5
) ]5 @5 Z0 ~8 k; K) l N/ @pts discontinued for financial reasons. After TKI discontinuation# ~ R2 @4 W' o: o: R! U4 e8 ^! Y
patients were followed for a median of 11 mos (5-131). Among pts with
5 Q/ }+ _+ M: KCMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a
/ y6 P G: C" u1 j6 P O% E' p4 lmedian of 4 mos (1-11) from discontinuation with median transcript level7 I! b, e2 d4 Q ~2 }
at relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF
6 L8 D; k; S! }5 gtherapy had CMR at time of TKI discontinuation, 50% of them relapsed.: o" ?" n' [. J# C, R
Among 7 pts who discontinued therapy in MMR, after a median follow-up
4 o \! v1 k0 {$ C5 _9 j; g9 ifrom discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,6 `' K; J& H) u6 _2 [) Y4 a$ L
one has minor CyR and one CCyR without retreatment at last follow up
7 O+ v1 T6 g+ nafter 78 and 105 months from TKI discontinuation, and one transformed to
- }8 F6 D$ V# ]+ Maccelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
/ p# H9 |) r0 P Zto MMR. Three pts had a transient molecular recurrence with spontaneous9 A9 Z! A8 R( n6 E# |! s5 [
re-gain of CMR. Seven pts with relapse were treated again with TKI, 3
7 y; F" [9 W' V( L$ w: A$ N2 ?with nilotinib, 2 with dasatinib, and one each with imatinib and' f* G4 ]( K1 w% w
bosutinib (the later in AP). After a median of 13 months on therapy
) A: t2 G7 s; l+ \2 N5 _- b9 F(range 4-52) all patients improved their response, 5 with CMR and 2 MMR- X" [0 \9 ~2 X% w: `
(including the pt that had transformed to AP). There were no deaths or6 B8 P2 i& n8 ?5 }
transformations to blastic phase of CML. At last follow up 14 (54%) pts
5 f% j8 J3 a* D$ Gwere in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
6 k' }1 t5 w0 T2 N% u4 wPCyR.
( c4 N: G: @' A. B3 z2 w& K; X# @, [$ U/ \3 o- F5 e
Conclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular
$ k4 ?# J6 M7 A/ mrelapse in nearly half of the pts who discontinue therapy in CMR. Some) l8 T4 B6 d; M0 e
pts who discontinue in MMR may have sustained MMR. Treatment+ L x$ N. X7 z! d/ G+ D
discontinuation should be considered experimental and cannot be
" m- d9 i+ }/ e( |7 K+ lrecommended to pts as a standard approach.& u: Z+ {3 m- b+ M& ^5 y' _
) b. E* Q' X3 R8 RDisclosures: Ravandi: BMS: Honoraria, Research Funding. |