MDACC has, for the first time, given their experience of TKI6 J8 T4 E% K* ?( f1 T
discontinuation. The doctors at MDACC look at 26 patients who( [8 ?" s( l. r
discontinued therapy from 2003-2012 for various reasons. These reasons" z* C8 d0 u) w6 R& ^! L4 `: J0 w
include long time in CMR, adverse side-effects, pregnancy and financial
0 M' R9 }- v5 Cconstraints. Please note that 17 patients discontinued therapy in CMR+ a& F* L6 b5 N* X6 w( S
and the rest in MMR. Of the patients in CMR who discontinued therapy,
* q% x) O" |! K( f47% had molecular relapse. Those in CMR who discontinued and had taken
& ?" g0 |+ ~5 e! @prior Interferon to a TKI, 50% relapsed. Also note that of these 26! h% C" h0 c6 s
patients, most had been treated with high dose Gleevec.9 h" h+ ~6 W' |( Z0 w) n, T
: S5 { f9 z' y"All patients discontinued therapy in CML-CP, all in CCyR, of them, 173 C8 q; W1 u; f* w% K) z* e
(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.: B- a$ D4 [ d3 ] B
The median duration of CMR before TKI cessation was 62 mos, (0- 118).
( l( U& D1 c1 ~5 \ b& jThe median duration of total TKI therapy was 101 mos (3- 135)."
?: ]/ x+ @4 {+ N0 w7 _1 w0 h* x- P5 e1 I+ t" F. p; q0 ]. g
Therefore, the median time in CMR before discontinuation was about 5% y0 C( @) u% M1 T
years. The median follow-up is only 11 months. The median time for
) J0 b4 T" K/ m) ^2 Mmolecular relapse of 8 patients who had been in CMR was 4 months and
! W6 A, h' q/ a* @they relapsed with median PCR value of 0.01 on the International Scale.
! a& B' y6 o- y% J2 ` u# _: s* O9 }; f
Of the 7 patients who discontinued when in MMR, 4 remained in MMR at a
8 |" L! t( X' g" O! W, m5 m; Wmedian follow-up of 21 months, 1 remained in CCR, 1 in active disease
5 u! I! c& F1 V$ ~& _and 1 transformed to accelerated phase off drugs. Therefore, from this i4 O# |' g3 S0 I/ S6 W( y
data, scarce as it is, there is a risk of transformation to advanced; F. u6 R4 M* o9 ~
disease if one discontinues drugs in MMR.1 R: f) s3 ]" ~$ [6 |5 ?$ s d
0 ?1 v/ O# I$ C9 W/ o) P) K2 patients were PCRU (4.5 log machine) and these patients relapsed: B k% `& j: ~. Q9 F B6 m$ C! F3 Z. e
into MMR when drugs were discontinued.
" ~! J) N, o" D- o: k, L
: |, K8 n! c( x, X- gSeven pts with relapse were treated again with TKI, 3 with nilotinib,/ v1 k9 Y7 ^% y
2 with dasatinib, and one each with imatinib and bosutinib (the latter
; V7 Q: _8 q; q6 win AP). After a median of 13 months on therapy (range 4-52) all patients
& \+ r2 u1 V; `+ u* @' B& D; Kimproved their response, 5 with CMR and 2 MMR (including the pt that had
; A; n' [- l3 ~ o4 Y8 Vtransformed to AP). They do not say why all patients were not retreated& _7 M7 ]( B8 Q: E) }% a* |
with imatinib and had to take Nilotinib and Dasatinib. Also, note that; p2 O. z& L* W9 u% q5 A" Q3 h4 g1 S
one did not regain CMR at the 13th month mark though it is good news
! m& t. X' r' x$ l' t5 W/ Zthat 5 did. It may take some time to regain CMR for some who have gone z: Y- s! g6 w
off drugs and relapsed. However, from our own list experiences, some3 b8 z& ^0 ]0 k
had regained CMR fast when they retook the TKI.% P1 M! }. F4 n
7 X. a! a3 L3 x
The doctors conclude that treatment discontinuation is experimental3 |1 X- s- s8 B5 @# Q. s
and cannot be recommended at this stage as a standard procedure.
# ]" y" I* j' ?5 b) R
?% Y/ O6 d, g8 rBest Wishes,
/ S7 Y3 g( O- Y4 i) Z0 d% H: [
) ?' B7 @. D7 A( ?9 SAnjana0 z* N8 _5 B( ~1 e) c
; A. t$ u' E" d r2 E/ x
" A' k% t% w0 t& }2 A# b& A8 a+ j, A
0 i: m1 w' ~( D! P
b5 K" m* `! \. d% ?4 ?
. @9 `+ v; N" J- X! D/ `6 G5 j
% p. ]5 U" T' J- P9 L+ ?
7 C6 a% i" ^7 i) Q2 f+ k
! {) r0 c8 N$ k5 m4 \) U. r P& }$ c) x* ]" `% N' N
- n+ ^! [2 k# H+ p* \
3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor: |# D* T% M& f3 v7 @& U
Theray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single i. i# w7 U4 K x1 ^
Institution Experience: E% J( @* G) ~7 L& A8 T5 |& K' |4 o5 _
Program: Oral and Poster Abstracts+ |/ Q, n: K# _
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III
1 A) v8 k" B4 q- z! D3 x5 O
; Q- W9 _" q- M n7 A1 G, m/ iMonday, December 10, 2012, 6:00 PM-8:00 PM
# s6 n" ~6 F2 n+ z S* H& Q& e' X+ |; M3 I, B) y
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)
3 y) E1 N/ ~6 M# l% n8 H# v/ S; o4 w! }% [3 \' x1 Y
Ohad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,6 l+ W7 I0 ~5 p9 T2 F: K9 f
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
{4 ^# g" b8 B. u* YStefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,
5 f: D" e3 ` m- R" }. M& Q9 j- Z" W' wGautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.
- }7 t+ n+ c0 ?2 zCortes, MD1
: b K# M8 D, L( h U& l/ T3 |* f3 U: v* f" S; v7 B
1Department of Leukemia, The University of Texas MD Anderson Cancer
/ ]5 C& f( V qCenter, Houston, TX
, f" q J! |# R7 }: r8 H2Department of Leukemia, The University of Texas M.D. Anderson Cancer
& @0 o0 ^* B! V0 X' }0 T) G* TCenter, Houston, TX O+ _: `2 p1 v G- W
, z; c( d7 `( t8 |" s/ EIntroduction: Some recent studies have reported on the outcome of CML0 G* D% |( O! j! P( ~
pts who discontinued thyrosin kinase inhibitors (TKI) after achieving+ |# m+ ~, P$ ~) ^, n- }
sustained undetectable bcr-abl transcript level. Most patients who stop& v. _ ?# g3 Y/ k9 U0 W
TKI have experienced molecular relapse. Most patients respond after/ p7 `: s- e6 D& W
resuming TKIs regaining undetectable bcr-abl transcript levels. These
' y" \3 A) V; Q8 |4 D: ?5 y4 Z7 Tseries have prospectively planned treatment discontinuation and included
# {( ^% }* a" ], Fonly pts that have sustained complete molecular response (CMR) for at
+ b1 N' J( n& fleast 2 yrs. However, in many instances pts may want to discontinue TKIs- ?! w p# p. u9 @8 k9 X) J
not in CMR. Various reasons may lead patients to discontinue TKI
: T) ^6 A: V1 W; s# a. gtreatment unexpectedly, among them severe adverse effects, pregnancy or* P+ l# o% R7 Y$ b- E
economic constraints. This single institution experience reflects the" s0 Y$ B2 c3 j# ^1 x: j' ~% T
heterogeneous nature of pt-driven TKI discontinuation.
a6 n- u. x7 [ C4 ?* ~
, @9 N! G9 \+ n, IAim: To characterize the outcome and profile of CML pts who chose to
5 d& b1 [( a9 W% p ndiscontinue TKI therapy in a single center regardless of their initial
+ S/ o. j, F" ~$ R& g4 s# u5 Yresponse to TKI therapy.1 R0 N* Z$ `0 ]+ A ]; u, I
9 S6 ^' R& Q& `9 p+ M* E
Methods:We retrospectively analyzed MDACC data on all patients with CML
2 M. ^$ \# O: J& u' s* [that were treated with TKIs in our institution and discontinued therapy.9 g: v# U; |" v8 N4 }3 Z* x
$ ~ N: }% Y- N$ a& A! `1 b
Results: A total of 26 patients with CML-CP managed at MDACC& q: i) V+ p+ s4 ~
discontinued TKI between 2003 and 2012. The total median follow up time, T r+ f5 ?" J8 @/ F2 k1 l a
since diagnosis was more than 120 months (mos) (range, 45 mos to 304
2 a2 P+ B- G4 O( amos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
3 x( A2 O5 n; f2 Mfemale. All pts had been diagnosed and treated in chronic phase.2 C+ g4 G8 {- e3 R* @
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI
& q d7 [, z. S* [( \( uas initial therapy (4 received imatinib 400mg/day, 10 imatinib, q( ?0 E E3 H& Q+ z5 G; r% y
600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with* a% b- ~2 g( H% S, |! h
IFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN! y9 v5 r' [/ s9 H
failure. Pts treated frontline with TKI started therapy within a median
3 ~4 ~: w: }. W) Q1 N5 f9 Cof 0.8 mos from diagnosis (range 0 to 4) and those with previous$ i }5 j3 b- p
interferon (n=11) after a median of 60 mos from diagnosis (31 to 164
, ?, V& u8 n; _/ f3 mmos). Before TKI discontinuation 21pts (81%) were receiving their first1 @# q4 Q9 U/ ]- j# k
TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete
% |; v3 o2 c4 X5 ]) }, C6 [) Ncytogenetic response (CCyR) had been achieved in all 26 pts at a median; ~$ ?) g( v% c5 ]& z- @" {7 t( x
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of
) l/ z2 Q. O$ S1 ^2 ~ b( H3 b9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All# u0 b4 T ^ p" V0 r
patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)
5 ~- \- V. L( C4 K% v4 z$ |1 {had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
# E& `# a9 g6 y0 C% X( rmedian duration of CMR before TKI cessation was 62 mos, (0- 118). The: ~$ F2 ^( \# t3 M( m
median duration of total TKI therapy was 101 mos (3- 135).
% i6 n' k( Y! @$ w( s% Q$ ?4 K% V
- T g+ X1 Z: {) M' E1 C, X1 M: fFourteen pts (54%) discontinued TKI due to adverse events, 2 pts
+ H( q9 V* `( Ydiscontinued to become pregnant, 5 decided to stop after long CMR, and 5
6 ^6 H8 w* O. r% f0 S/ vpts discontinued for financial reasons. After TKI discontinuation& a% C/ I/ R( p# q7 Z' Q! `% j
patients were followed for a median of 11 mos (5-131). Among pts with
* M9 t0 f( k, c' \CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a
/ @' t* L3 O' z6 q& z) q' kmedian of 4 mos (1-11) from discontinuation with median transcript level
7 Y8 H8 a- |( `, x1 Jat relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF- T$ o$ s, l( K4 x- H
therapy had CMR at time of TKI discontinuation, 50% of them relapsed.7 u- B/ ]* J* @6 r" m% c2 ~( i
Among 7 pts who discontinued therapy in MMR, after a median follow-up
% Z9 R0 N, v" @+ r3 Vfrom discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
' r9 Z) Y3 F& F1 T; h+ Yone has minor CyR and one CCyR without retreatment at last follow up
2 \$ } z4 o/ j' h2 ~after 78 and 105 months from TKI discontinuation, and one transformed to) w* o; |0 T& N
accelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
/ p# Y( a/ H2 W' Q5 B, {7 Z5 oto MMR. Three pts had a transient molecular recurrence with spontaneous5 _6 B6 M) L, ~4 `# a# J
re-gain of CMR. Seven pts with relapse were treated again with TKI, 3( K% B1 u" e: D$ q/ b2 r/ h% V
with nilotinib, 2 with dasatinib, and one each with imatinib and* }6 _7 p& W8 a* K! t' v: Y9 x' V
bosutinib (the later in AP). After a median of 13 months on therapy
7 S7 Y% B% \$ i! m: d4 k6 p" k8 e(range 4-52) all patients improved their response, 5 with CMR and 2 MMR! G5 B7 g% P- ~: t
(including the pt that had transformed to AP). There were no deaths or0 Z* h) E# U t0 y; ?% T
transformations to blastic phase of CML. At last follow up 14 (54%) pts! @/ `' u7 d9 G) _5 q
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
/ U4 x1 B9 {5 fPCyR.
( M2 K3 S! c2 n4 t( b9 B: x8 f; s
7 B% K+ H4 N2 Y. F6 e7 a3 OConclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular
( K% a b; h7 K9 f7 g( Trelapse in nearly half of the pts who discontinue therapy in CMR. Some
% v( M$ [; }/ tpts who discontinue in MMR may have sustained MMR. Treatment% p. i9 I/ ~0 d; u! Y- n5 B
discontinuation should be considered experimental and cannot be
# F" G( S. l# [8 H wrecommended to pts as a standard approach.
8 A3 i7 s+ |( l7 _) ?7 G& s8 y; Y* k, b' M# E
Disclosures: Ravandi: BMS: Honoraria, Research Funding. |