MDACC has, for the first time, given their experience of TKI
6 w9 M1 a. S. x5 S% vdiscontinuation. The doctors at MDACC look at 26 patients who
' B- _9 J1 m: `" ddiscontinued therapy from 2003-2012 for various reasons. These reasons
0 n' w8 g$ z/ P* Jinclude long time in CMR, adverse side-effects, pregnancy and financial n, U# L& l- K
constraints. Please note that 17 patients discontinued therapy in CMR2 X) _ t5 A8 Q& d2 l1 j8 b8 M
and the rest in MMR. Of the patients in CMR who discontinued therapy,
% s* M/ U5 E J47% had molecular relapse. Those in CMR who discontinued and had taken
9 g0 g$ C1 t+ t w! xprior Interferon to a TKI, 50% relapsed. Also note that of these 26
2 ?* ^3 @9 k" K! Opatients, most had been treated with high dose Gleevec./ ?# ]! V! L U3 ^9 `
$ u5 j" T/ X/ J"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17
6 `5 u( z6 |9 _7 ^ }1 K n(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.9 ?- }0 x" |! X% u: n
The median duration of CMR before TKI cessation was 62 mos, (0- 118).4 F$ n6 T; i7 Y
The median duration of total TKI therapy was 101 mos (3- 135)."
4 J+ G+ j+ D0 Y: l3 G# w
/ J& J" }4 z. g4 e4 v, L. c- A [' YTherefore, the median time in CMR before discontinuation was about 5. [9 S+ r, N b$ Z, }
years. The median follow-up is only 11 months. The median time for
5 {7 Z& @# @9 K4 W, R! Amolecular relapse of 8 patients who had been in CMR was 4 months and
4 ~4 n/ F$ E% H9 C) [they relapsed with median PCR value of 0.01 on the International Scale.1 A) A/ r0 o' Z% o3 t
; {# P" o0 {0 y( eOf the 7 patients who discontinued when in MMR, 4 remained in MMR at a
6 @! z; G' C, h6 Fmedian follow-up of 21 months, 1 remained in CCR, 1 in active disease
* x0 O! E# y, {: {, Pand 1 transformed to accelerated phase off drugs. Therefore, from this' i8 ~; x1 N* i
data, scarce as it is, there is a risk of transformation to advanced
1 o# @6 ^. V/ q' Z( ddisease if one discontinues drugs in MMR.
9 n5 O0 ~& S" o6 o
+ O/ h7 W8 H1 u9 k2 patients were PCRU (4.5 log machine) and these patients relapsed t* v0 [7 w/ I) q) G
into MMR when drugs were discontinued./ ?( N; F! m3 h7 K, U
9 g+ E! J! B& y& M% \
Seven pts with relapse were treated again with TKI, 3 with nilotinib,) q9 d Q! e# t& }; ^, z& o
2 with dasatinib, and one each with imatinib and bosutinib (the latter
6 `( r8 j8 @* win AP). After a median of 13 months on therapy (range 4-52) all patients$ |+ m4 z3 u2 ~5 N- v+ q# l
improved their response, 5 with CMR and 2 MMR (including the pt that had' u/ q4 u$ z1 s- d) Y+ R6 v: u7 ^" |
transformed to AP). They do not say why all patients were not retreated
& @3 l; ?. m* ~1 o1 r- rwith imatinib and had to take Nilotinib and Dasatinib. Also, note that! G s- z1 U, d/ c( \) R
one did not regain CMR at the 13th month mark though it is good news
- e9 Q) Y- i) r2 S+ \" C, k9 R& xthat 5 did. It may take some time to regain CMR for some who have gone
" ?, a8 P' o6 f/ u: q7 |- j1 _) H2 poff drugs and relapsed. However, from our own list experiences, some
' y% S3 K3 s1 w$ Z& Ehad regained CMR fast when they retook the TKI.
$ l0 {6 @% D/ Z' A3 B- U( x, S8 Z0 O: a2 T$ [# u
The doctors conclude that treatment discontinuation is experimental ~: ^% j8 G8 F
and cannot be recommended at this stage as a standard procedure.* q' w0 P8 X$ H0 L, G: a
, A; k% X8 a6 n1 E$ w8 a& y: |$ ], Q
Best Wishes,
2 j' d+ A2 l8 n$ f% Y% C% X- e& Z. t" `
Anjana
3 @( H; ~! d6 P4 G$ R( o, s+ E9 f9 o
5 g2 L G) Q5 J
0 l% P; z. t, K7 p5 I8 u& r& p0 M) }2 }9 c
; m8 k# G% Q5 }0 U3 R2 k+ l6 X2 c- r
5 H4 F1 Q- ^- O# D$ `# I1 i! D9 T" t
" g0 Z; w* b; Y/ N0 R+ q' s% n1 _+ P# S% C: n
( N+ v. c2 b, R2 c8 h. i, I8 w( o3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor
/ g6 P. T! l: f qTheray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single# ?3 L9 P! b( ?* ], s
Institution Experience# G5 v C2 e: g. U
Program: Oral and Poster Abstracts& Q, {% x$ O# s
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III
& Q' `9 ^, _6 [# F3 d; t5 h7 W6 a$ K3 U* S6 k w" ^
Monday, December 10, 2012, 6:00 PM-8:00 PM/ T: J/ d8 p7 o: H8 ^- X/ i% |
$ I. q: _- R6 y; I/ NHall B1-B2, Level 1, Building B (Georgia World Congress Center)3 c0 G- i( R: |
" `% p0 J _& x$ U2 b: L |) R' u
Ohad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,
! h$ X' v5 `% Z$ Z4 Q' m! t- AElias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
0 g" [+ G) Y1 i5 y1 } N- nStefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,
8 r, i7 V( U% N2 c( d( r9 C( A# HGautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.
5 @+ R y1 i+ uCortes, MD1
& f: c& e* G& S- y" o) a' ?: k- m9 \' z4 `- J( ^7 y' V6 l$ x
1Department of Leukemia, The University of Texas MD Anderson Cancer t5 \3 Q: j% r2 ^4 G
Center, Houston, TX
0 c3 u7 W# }) u/ S2Department of Leukemia, The University of Texas M.D. Anderson Cancer
) I3 C4 U: Q! ]1 @8 ACenter, Houston, TX( q/ O, t8 P) N$ {# ^" T/ B1 {
, T# G9 c/ i# c* x4 X) lIntroduction: Some recent studies have reported on the outcome of CML- b7 r% d( ?# S- Z _7 u+ y9 B, p
pts who discontinued thyrosin kinase inhibitors (TKI) after achieving3 Y9 e- p" v1 N' U2 `
sustained undetectable bcr-abl transcript level. Most patients who stop
. f% Z9 F& b4 A, T5 R" h' p j5 N* e# \TKI have experienced molecular relapse. Most patients respond after" @- a2 m( r; M, d4 S# J
resuming TKIs regaining undetectable bcr-abl transcript levels. These8 ?! s; H3 |& u( }' e5 E
series have prospectively planned treatment discontinuation and included
& Y5 |3 r) K) ionly pts that have sustained complete molecular response (CMR) for at
, u: x2 P+ c7 G- [% ]- Zleast 2 yrs. However, in many instances pts may want to discontinue TKIs
, g: X9 U$ \- p( jnot in CMR. Various reasons may lead patients to discontinue TKI0 I0 o7 @& j3 L; y: V
treatment unexpectedly, among them severe adverse effects, pregnancy or
4 p1 R3 r) g9 Q9 reconomic constraints. This single institution experience reflects the
* J5 s2 c" L6 D8 j. W. ~heterogeneous nature of pt-driven TKI discontinuation.8 S% g% L0 s" ?5 E: Y+ v
: j' l' {; l' h4 ^9 y$ j2 R- ~
Aim: To characterize the outcome and profile of CML pts who chose to
e) s; v1 _ kdiscontinue TKI therapy in a single center regardless of their initial
. H- F4 O6 g* Y- Lresponse to TKI therapy./ | _. n' V+ l
% u$ C, C0 y+ RMethods:We retrospectively analyzed MDACC data on all patients with CML
5 o% A9 S% ~6 ^6 j0 Mthat were treated with TKIs in our institution and discontinued therapy." N* h h- t: [ W% t# T' t
4 b' v$ O: m5 A( w# pResults: A total of 26 patients with CML-CP managed at MDACC' ^0 k$ H( Y$ f' z
discontinued TKI between 2003 and 2012. The total median follow up time
* e9 g( v- o( N4 Z) Usince diagnosis was more than 120 months (mos) (range, 45 mos to 304
$ v5 C/ l. N5 j+ h* e+ [2 Hmos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
7 h) o6 Z0 D2 U$ ^2 Nfemale. All pts had been diagnosed and treated in chronic phase./ P" r7 G% f- h& W2 M8 W2 q
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI9 x: B* R. A. _% V
as initial therapy (4 received imatinib 400mg/day, 10 imatinib% f7 k( ~2 g; U' J0 k; ?
600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with; D6 T8 ~0 h6 V, Q2 ?
IFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN
; k: F# f3 ~& U& D( o3 q6 [' h1 {failure. Pts treated frontline with TKI started therapy within a median
( ]! i: l' Q1 o( h( J& d# K# p8 Vof 0.8 mos from diagnosis (range 0 to 4) and those with previous
4 i$ G5 J1 ]; l" g9 Jinterferon (n=11) after a median of 60 mos from diagnosis (31 to 164; b( w, l9 }+ a6 A( h5 D, v
mos). Before TKI discontinuation 21pts (81%) were receiving their first
% Q. b$ @1 e0 |- p2 G5 m$ ?: hTKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete
2 P6 t1 ?5 E; a5 } _0 f( Y1 ocytogenetic response (CCyR) had been achieved in all 26 pts at a median0 E! l. ^) I8 V2 Y2 x5 ?/ B
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of
% G; O3 z6 e% h, t6 t# ^5 T9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All
" t/ _* a- A) j- kpatients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)2 K4 {% R1 D. l& J/ |3 t
had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
Z! ~$ C0 \7 ]median duration of CMR before TKI cessation was 62 mos, (0- 118). The
! l8 S! f' U4 `' L+ G/ mmedian duration of total TKI therapy was 101 mos (3- 135).
4 ~: G' h, ~+ {" c* O
1 A: v5 a8 G2 o0 ?Fourteen pts (54%) discontinued TKI due to adverse events, 2 pts2 a8 M M: j/ ] a# W' s
discontinued to become pregnant, 5 decided to stop after long CMR, and 5
& _2 N: _" T7 h! kpts discontinued for financial reasons. After TKI discontinuation. C8 [. c, \! w
patients were followed for a median of 11 mos (5-131). Among pts with, V& `, B! X7 h* z# Q
CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a
, }3 q, q, s$ t5 Vmedian of 4 mos (1-11) from discontinuation with median transcript level1 F/ R. T. s" Z" o- Q
at relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF
) Y$ l& k1 M# K( r+ i$ h2 {, Btherapy had CMR at time of TKI discontinuation, 50% of them relapsed.1 f; S# K2 W2 `( [* k
Among 7 pts who discontinued therapy in MMR, after a median follow-up
, K9 b1 D4 C! q1 E9 y* r Nfrom discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
+ b/ e3 M5 h7 O: j) |one has minor CyR and one CCyR without retreatment at last follow up
( [6 e; y% F0 kafter 78 and 105 months from TKI discontinuation, and one transformed to
|+ t$ ?2 O7 u) l/ ^ waccelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
2 q7 |5 z6 s/ g( E. \6 D: W5 _to MMR. Three pts had a transient molecular recurrence with spontaneous
& K3 z" i2 r6 _; ^0 D5 ore-gain of CMR. Seven pts with relapse were treated again with TKI, 3' R. T8 s4 q! P+ }" R
with nilotinib, 2 with dasatinib, and one each with imatinib and; G; j) V4 g! p" Z5 O3 B. L
bosutinib (the later in AP). After a median of 13 months on therapy; V t6 }* `, O- a9 A7 q
(range 4-52) all patients improved their response, 5 with CMR and 2 MMR ^( F/ d$ M4 W: C) ?% w% c% e( ?
(including the pt that had transformed to AP). There were no deaths or% w( Q: B# {/ O: t8 S
transformations to blastic phase of CML. At last follow up 14 (54%) pts
7 B$ e* o8 c z Q& Zwere in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
5 @* P$ b0 j' C! x9 ~PCyR.. n5 M3 y3 {6 W. f
( ^9 A5 \6 f7 A) ]) [$ }$ j
Conclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular
1 N6 ?. ]* a( W" E* F; T: yrelapse in nearly half of the pts who discontinue therapy in CMR. Some
+ t" U& u6 F1 ^pts who discontinue in MMR may have sustained MMR. Treatment& N& x1 N) [9 f7 r
discontinuation should be considered experimental and cannot be( s( K2 p& @. Y( e( I
recommended to pts as a standard approach.
) C% v3 M( ^2 ` [
( x, P K& P# g" G/ gDisclosures: Ravandi: BMS: Honoraria, Research Funding. |