MDACC has, for the first time, given their experience of TKI6 E/ L$ P7 U5 B( D: ` S
discontinuation. The doctors at MDACC look at 26 patients who: t- ?1 N% m; m7 t0 X$ J
discontinued therapy from 2003-2012 for various reasons. These reasons
9 w! k( q, F8 N! l8 Rinclude long time in CMR, adverse side-effects, pregnancy and financial
/ e. Z; y/ c0 E* @! kconstraints. Please note that 17 patients discontinued therapy in CMR5 U8 q9 n" ?8 [% F9 c
and the rest in MMR. Of the patients in CMR who discontinued therapy,
4 J9 V3 y* O a: A47% had molecular relapse. Those in CMR who discontinued and had taken, q7 v& L: t! ^* } M
prior Interferon to a TKI, 50% relapsed. Also note that of these 26. W7 p6 ]8 E# H9 `7 M$ \
patients, most had been treated with high dose Gleevec.
$ i1 u, k- I& a5 t# v
/ ?; }9 z+ X* u# O7 O* n& f"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17
) \( z) D+ z5 m9 S0 H. o5 s(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.
/ |7 {) N- M1 I' I) N7 tThe median duration of CMR before TKI cessation was 62 mos, (0- 118).2 |1 A# q2 a% E* J1 j% F# G
The median duration of total TKI therapy was 101 mos (3- 135)."
, U% K0 g+ t2 O7 q6 P% R3 x8 o$ W9 S5 C1 k' j, O
Therefore, the median time in CMR before discontinuation was about 5
5 s0 n5 H Y% D0 h; h' Gyears. The median follow-up is only 11 months. The median time for8 v! e1 ^1 P6 a5 _$ O) N8 C, A9 s4 P
molecular relapse of 8 patients who had been in CMR was 4 months and3 K8 v' A' C" w0 l. Q4 k( |
they relapsed with median PCR value of 0.01 on the International Scale.
* B2 ~/ s ^0 L9 j. k1 Z! W3 n8 Z+ C7 y* W) m- V4 z% ^
Of the 7 patients who discontinued when in MMR, 4 remained in MMR at a# y2 `" d# _5 o/ ^& v$ k/ H+ q1 |
median follow-up of 21 months, 1 remained in CCR, 1 in active disease# i [" Y. C* g- a' F' m% v
and 1 transformed to accelerated phase off drugs. Therefore, from this
. Z2 t& w, I) ]data, scarce as it is, there is a risk of transformation to advanced
9 N5 V5 Y+ v L Sdisease if one discontinues drugs in MMR.* `$ X& s2 |: L2 q/ F" S0 ^
0 N. i2 S! L D2 patients were PCRU (4.5 log machine) and these patients relapsed; z( N7 X; _( @, q
into MMR when drugs were discontinued.
$ B* S7 Z0 z3 m' x$ q0 F) V. C0 |4 r" W1 P4 Y2 v- e
Seven pts with relapse were treated again with TKI, 3 with nilotinib,' Q& x: ^ d( Y+ C0 O+ c
2 with dasatinib, and one each with imatinib and bosutinib (the latter$ o" V* D& M& ]8 l/ [5 n
in AP). After a median of 13 months on therapy (range 4-52) all patients
( X! w! u" L; iimproved their response, 5 with CMR and 2 MMR (including the pt that had
7 S2 r1 ]/ {. e5 u* [) l2 Etransformed to AP). They do not say why all patients were not retreated
! _3 b% b# w8 a0 ^with imatinib and had to take Nilotinib and Dasatinib. Also, note that: F4 _+ x- {- W, O& `6 ?7 A
one did not regain CMR at the 13th month mark though it is good news Q: q* x: f' F3 v: G: w# H7 ~
that 5 did. It may take some time to regain CMR for some who have gone4 o" ?( {% @* s9 ^9 V9 n
off drugs and relapsed. However, from our own list experiences, some
& f2 z: L8 I Uhad regained CMR fast when they retook the TKI.
! p+ z6 x9 o5 X" e& K+ U3 l* f4 ^" p9 c/ g' G& i5 N
The doctors conclude that treatment discontinuation is experimental
- K) S+ V$ h# c2 t: G! Yand cannot be recommended at this stage as a standard procedure.+ f. T% L! ~/ n2 [9 J
! x% Q5 d& M; K( `7 TBest Wishes,
1 A/ P `6 K" r3 k( w8 E8 p7 m# G
Anjana
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3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor# z: |1 ~ g4 x+ ?
Theray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single: Z2 J& D8 }( v+ l% o# T! e
Institution Experience7 o( ? d4 b0 b$ \9 u
Program: Oral and Poster Abstracts9 g2 l! {( E' N, x) b* w- V
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III$ H8 h3 l- h# X& ~2 f+ X- N" L
/ k" w8 t2 j; [ S. A6 sMonday, December 10, 2012, 6:00 PM-8:00 PM
: Y- o3 J `* g) K5 \6 ^
) i. o. A% z0 L* F' eHall B1-B2, Level 1, Building B (Georgia World Congress Center)
; S" @$ A' B4 z5 M8 b
8 Q* ?5 _; Q; a* `' g- JOhad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,! ^6 _: S: W% g8 ~( ]0 z
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,9 p* [9 D* Y* x6 F. K% J8 n4 G! Z! {
Stefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,( n# E1 o- b: p: R2 Z' V
Gautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.
+ ] P6 Z w7 d( _/ b+ |Cortes, MD1
$ t0 p. q9 L+ |, u* {( J f5 R* a+ S5 _9 Q
1Department of Leukemia, The University of Texas MD Anderson Cancer
! { _1 E, M. G6 `* LCenter, Houston, TX8 @, x' j- ?2 D& P( m _
2Department of Leukemia, The University of Texas M.D. Anderson Cancer
! i! E; ^. h7 J3 BCenter, Houston, TX1 e$ Y; W. H- d) N B
! c$ Q$ W% c( EIntroduction: Some recent studies have reported on the outcome of CML. O+ S( e8 m0 E$ v% y4 |1 n# J
pts who discontinued thyrosin kinase inhibitors (TKI) after achieving' ^8 L8 D6 r! X
sustained undetectable bcr-abl transcript level. Most patients who stop: ~' }7 N: w1 N! Y @( o* @
TKI have experienced molecular relapse. Most patients respond after; t( r) _1 g3 k6 z* T3 {+ i! ~
resuming TKIs regaining undetectable bcr-abl transcript levels. These
6 x/ M/ I' v2 v8 W. n1 ]series have prospectively planned treatment discontinuation and included
* f$ \7 a8 l, w, V% r" A4 ~! |2 E" t2 Y; F/ Gonly pts that have sustained complete molecular response (CMR) for at
7 n9 J, G6 G! i2 _. Bleast 2 yrs. However, in many instances pts may want to discontinue TKIs' S# i/ B; C; V; _6 }
not in CMR. Various reasons may lead patients to discontinue TKI
; X* ^: t- x! ]* mtreatment unexpectedly, among them severe adverse effects, pregnancy or$ K. y6 u$ q+ K3 p7 C# t; K
economic constraints. This single institution experience reflects the
; }% D Y1 g* E3 Zheterogeneous nature of pt-driven TKI discontinuation.% g6 u9 E1 [" j2 }2 k5 F
2 \* f: ]; j3 B( q7 h8 s! d8 I4 e
Aim: To characterize the outcome and profile of CML pts who chose to
- e: R' @6 P3 Adiscontinue TKI therapy in a single center regardless of their initial
1 |# L% N5 }$ S o5 bresponse to TKI therapy.
2 s6 `, i- z% C. x" j/ T0 N
# Y9 t, F9 d- ]/ ~, w! RMethods:We retrospectively analyzed MDACC data on all patients with CML2 e* r$ K" e0 e5 c# d
that were treated with TKIs in our institution and discontinued therapy.
- v$ j; C6 g$ T4 z9 z% ]# k; n$ F" u* r; {
Results: A total of 26 patients with CML-CP managed at MDACC
: A( e3 O& Z4 F) @7 Y- v$ _0 rdiscontinued TKI between 2003 and 2012. The total median follow up time/ G- `7 W* R# ^; o# f7 E
since diagnosis was more than 120 months (mos) (range, 45 mos to 304
5 d5 C' t: S; @# G+ Hmos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were0 C7 ?4 E8 L8 c0 S5 J, b7 Z
female. All pts had been diagnosed and treated in chronic phase.
1 S h. x: |9 i8 z, M9 W+ ~* nInterferon was initial therapy in 11 pts (42%) and 15 pts received TKI
5 @) f, Q" C( n# Uas initial therapy (4 received imatinib 400mg/day, 10 imatinib: c$ l$ O; i9 M" f4 i& [! C' J6 f
600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with4 `% n% M1 j) H0 U* |6 V
IFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN
6 m- O. R$ f; ?3 Ufailure. Pts treated frontline with TKI started therapy within a median( ?& Y4 O0 X8 F. l
of 0.8 mos from diagnosis (range 0 to 4) and those with previous8 b* { _' w. O2 W
interferon (n=11) after a median of 60 mos from diagnosis (31 to 1645 A9 o0 e7 |) y
mos). Before TKI discontinuation 21pts (81%) were receiving their first6 u; S/ c# c/ j( \6 f
TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete( x9 s8 }/ U. f j/ E' b
cytogenetic response (CCyR) had been achieved in all 26 pts at a median
* M# p! ?4 N5 G/ B, g2 z; Gof 3.5 mos (3-93); Major molecular response (MMR) in all at a median of; @# d6 M; a! _- Y
9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All: a5 X1 n9 u: ]1 d4 k/ {: l
patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)
, v7 f E9 ^0 u, ?& C& @, T7 Zhad undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
) R, n+ o7 Y# _! Nmedian duration of CMR before TKI cessation was 62 mos, (0- 118). The* o$ z1 C3 n" w0 d
median duration of total TKI therapy was 101 mos (3- 135).9 l ]+ u3 v! l, A
: H4 k/ y1 X; [# Y& j" a0 @ [- DFourteen pts (54%) discontinued TKI due to adverse events, 2 pts
4 L! N3 N* o: @3 P' L* C" tdiscontinued to become pregnant, 5 decided to stop after long CMR, and 5
3 L: G; s* J/ i2 N2 Lpts discontinued for financial reasons. After TKI discontinuation3 H4 t4 s( z# N: P, `
patients were followed for a median of 11 mos (5-131). Among pts with
/ F% y4 c: P, D; V; P. `CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a
# |4 m$ w6 x: z0 a) S! o4 B; lmedian of 4 mos (1-11) from discontinuation with median transcript level7 S* i, U7 N+ j' b0 t [" ]0 n
at relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF! z, b7 Z Q) E7 \) ^/ W
therapy had CMR at time of TKI discontinuation, 50% of them relapsed.* A' y% P' N- L6 o% g& {% q, S8 h
Among 7 pts who discontinued therapy in MMR, after a median follow-up5 A) D* d7 B( ^: S
from discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,) D5 H# g5 E/ f' a/ z1 p3 @
one has minor CyR and one CCyR without retreatment at last follow up
; k! P& D/ i Bafter 78 and 105 months from TKI discontinuation, and one transformed to; V: x% a8 b1 L! m. Z
accelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed5 w7 e+ q3 l4 c' m
to MMR. Three pts had a transient molecular recurrence with spontaneous
5 X8 F& d( I. wre-gain of CMR. Seven pts with relapse were treated again with TKI, 3
! j! u) ~. F3 i: C! M, E, ]) \; Swith nilotinib, 2 with dasatinib, and one each with imatinib and7 P+ Y! @0 w' a! l9 B2 h+ o7 H
bosutinib (the later in AP). After a median of 13 months on therapy
% j1 O" _: w; A5 {& V( s(range 4-52) all patients improved their response, 5 with CMR and 2 MMR
8 D5 `* |9 K& a0 t& f(including the pt that had transformed to AP). There were no deaths or, p9 V- \/ ^" M- {( Y3 @
transformations to blastic phase of CML. At last follow up 14 (54%) pts+ F; j7 p* Z" M) _
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
5 T: o' g' c! {: ^- HPCyR.6 D- f" x8 E) d4 G7 r( K' a
) E) u1 ~' O% z+ ^
Conclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular
$ D/ u5 T' P, Y* ^relapse in nearly half of the pts who discontinue therapy in CMR. Some
+ p( { }& ?# L9 d" dpts who discontinue in MMR may have sustained MMR. Treatment
2 r9 I9 q" g: z, Wdiscontinuation should be considered experimental and cannot be
- x/ p5 K) h; l! N) G8 V! B2 Trecommended to pts as a standard approach.& s3 `" Z9 O3 U2 j2 e
6 K$ R# r. v- w( s6 a7 u; ^Disclosures: Ravandi: BMS: Honoraria, Research Funding. |