MDACC has, for the first time, given their experience of TKI4 I. q) \# b3 I; I( W ]
discontinuation. The doctors at MDACC look at 26 patients who5 a+ o: V2 q" y7 W7 s1 q# ]) U
discontinued therapy from 2003-2012 for various reasons. These reasons
- U3 l6 R5 }! d) O; y8 k: linclude long time in CMR, adverse side-effects, pregnancy and financial
z% h+ n+ r" H; Qconstraints. Please note that 17 patients discontinued therapy in CMR
$ t: f1 }9 K7 a1 D6 y/ c1 kand the rest in MMR. Of the patients in CMR who discontinued therapy,
1 ^# Y* k5 O8 N( e5 T47% had molecular relapse. Those in CMR who discontinued and had taken# s; S( Z4 N J; T1 C$ T
prior Interferon to a TKI, 50% relapsed. Also note that of these 26
4 \! m& Y. Q- u; Qpatients, most had been treated with high dose Gleevec.
6 u2 m7 x3 }$ H1 o; t3 e- C' Q A# \7 g6 N" H6 I. D7 e9 ~; V+ H
"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17
/ ~! n9 a6 C+ P/ M: c6 Q x(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.# q; k: l/ D$ { K: H
The median duration of CMR before TKI cessation was 62 mos, (0- 118).
+ `5 H/ ~8 o$ D3 g$ A- ~7 xThe median duration of total TKI therapy was 101 mos (3- 135)."5 _( t- R, [. U/ w' r. p
W) U- k% v" L$ b( ~
Therefore, the median time in CMR before discontinuation was about 5
" w. y- ^; w+ R/ d G1 ^9 ?years. The median follow-up is only 11 months. The median time for' N) f6 E" r( N9 s* Z' `" J# A" k
molecular relapse of 8 patients who had been in CMR was 4 months and
) H: U6 `2 u6 B5 xthey relapsed with median PCR value of 0.01 on the International Scale.# n$ C: i) C1 P, A8 i
' O$ X0 v- n, B6 \' cOf the 7 patients who discontinued when in MMR, 4 remained in MMR at a6 F# Z" w/ y- }3 x' G
median follow-up of 21 months, 1 remained in CCR, 1 in active disease
; K( @* C# Y' `" Cand 1 transformed to accelerated phase off drugs. Therefore, from this3 E: |% d: R8 o& @5 X
data, scarce as it is, there is a risk of transformation to advanced
2 L( b% \7 \5 l" f) C& s6 U7 `% B/ Hdisease if one discontinues drugs in MMR.
* e, v: f Z$ J' H! O( S( Y6 A& E: f! |0 R; _
2 patients were PCRU (4.5 log machine) and these patients relapsed
3 Q( v8 P4 F: n( C1 a2 Yinto MMR when drugs were discontinued.
* O6 |$ N2 ]. T1 g& s ?7 I2 ]8 ~( I' E
Seven pts with relapse were treated again with TKI, 3 with nilotinib,$ r" c3 e: D3 ^. R6 w
2 with dasatinib, and one each with imatinib and bosutinib (the latter
& _" B. v% b4 N$ S( g) {in AP). After a median of 13 months on therapy (range 4-52) all patients: P% x# [! K9 _6 i6 d9 t
improved their response, 5 with CMR and 2 MMR (including the pt that had2 ^* x" N( D! a6 W; T/ Q N P
transformed to AP). They do not say why all patients were not retreated
9 l0 G% T! n% ~6 E; e9 ]with imatinib and had to take Nilotinib and Dasatinib. Also, note that6 ]5 n( Z! e% |# c
one did not regain CMR at the 13th month mark though it is good news
# F$ x" n5 f& ?- m6 h) Sthat 5 did. It may take some time to regain CMR for some who have gone# q% a( V( n' |. b4 d3 d* |
off drugs and relapsed. However, from our own list experiences, some
! ?' `& U5 E9 v! T( V7 Y( r5 Zhad regained CMR fast when they retook the TKI.
. I D1 r! _% r& p# U; W
: Y5 A/ [6 W( g# d1 w% L. _3 FThe doctors conclude that treatment discontinuation is experimental
9 \5 y! u8 ?* g( [) t; Hand cannot be recommended at this stage as a standard procedure.: s8 B* p' G& ]! X# X; Q4 d( x# B
* {% h, y7 Z$ l1 _/ XBest Wishes,
, }4 V3 J p1 V' u8 t0 v! c; }' l7 ~" o
Anjana V9 w" e4 O" Z$ P; h A
1 M% H7 x& Q! ~" Z2 L
[ a7 g2 d" B8 |0 E2 K5 e4 A8 I, `, U& `, l( w. s
, k( y3 F5 m' Z( y! b( G7 b0 ^. u6 U7 @4 k% T9 ^6 e+ z4 ?: u
. c0 `( i+ h8 F/ P
* p% v9 P$ T/ u; B& z( ]! O! q# K! }
6 b7 x: I, U# C& ^# t8 Z, y
$ \' t8 i+ N9 ^8 |+ Y7 M3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor0 j% |( Z% v7 ^4 @' v
Theray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single
4 X% I2 P, U- H' H6 d$ IInstitution Experience
4 p2 [- d% N4 \4 E; t' ~Program: Oral and Poster Abstracts: U b$ _3 N( P" ^
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III
- T: A# V9 [% j; `
0 A y/ x# y5 N* j! xMonday, December 10, 2012, 6:00 PM-8:00 PM
0 y) X! `) d' y g7 @
) n+ `/ O+ }! {- u" SHall B1-B2, Level 1, Building B (Georgia World Congress Center)8 X/ X% s$ x3 V; d0 N7 e2 s# k, G( F
. P& z: ~( j# g1 T
Ohad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,6 h6 e" T. }& I N4 b
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
# a; G2 E* g6 {% v1 s m* @$ nStefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,+ y- k8 f! A0 g- j
Gautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.8 j+ J$ F8 m5 n. E1 |( F# Z
Cortes, MD12 `" _ |1 k. r( c0 F
& N/ _% ]% ]5 W, [& E1Department of Leukemia, The University of Texas MD Anderson Cancer5 Y2 L9 L4 o9 _- E
Center, Houston, TX. [0 E1 K. K/ t0 A
2Department of Leukemia, The University of Texas M.D. Anderson Cancer, `3 ~, g( I5 Z! m6 a# G
Center, Houston, TX
* n; b/ c9 m! o1 o
$ _. f% h5 `0 G8 w6 t' A: j6 O7 xIntroduction: Some recent studies have reported on the outcome of CML2 L7 J4 V' x, u) d
pts who discontinued thyrosin kinase inhibitors (TKI) after achieving
/ U, ]8 F# e5 Csustained undetectable bcr-abl transcript level. Most patients who stop; q( ? T; ~) K( t
TKI have experienced molecular relapse. Most patients respond after
, i, |! f+ \( {1 kresuming TKIs regaining undetectable bcr-abl transcript levels. These
* }, ~4 D6 G" s- q. c* ]4 q, Dseries have prospectively planned treatment discontinuation and included; @$ ^4 B+ o/ k2 ?* p/ `+ U' c+ L4 h
only pts that have sustained complete molecular response (CMR) for at9 L* x! O4 P* _+ T, M) u
least 2 yrs. However, in many instances pts may want to discontinue TKIs
4 J3 a3 A, t# E: V1 K+ t" n1 dnot in CMR. Various reasons may lead patients to discontinue TKI5 X1 t6 G% T- j; d
treatment unexpectedly, among them severe adverse effects, pregnancy or
+ {5 o3 C( Z( d9 o$ T7 u1 }economic constraints. This single institution experience reflects the4 X% `$ K8 p# W5 r5 |1 ^2 E: H, ?, Q; m
heterogeneous nature of pt-driven TKI discontinuation.' l N& r- R5 W, r
) ]& t. V! m& W3 a- a
Aim: To characterize the outcome and profile of CML pts who chose to
# X6 b& X9 Q5 ~7 F6 r0 Ediscontinue TKI therapy in a single center regardless of their initial
& U8 Q9 e8 k6 G3 G4 [) gresponse to TKI therapy.
4 J' }) g( D7 {; I$ i6 \* J0 S Y
) p4 u, t7 p+ R) g' oMethods:We retrospectively analyzed MDACC data on all patients with CML9 g: ?) o9 Q: i* _2 N( ~' e
that were treated with TKIs in our institution and discontinued therapy. F, n7 d) k; k1 j
C9 H. @' ^" F0 I0 R2 Z' `# q& K
Results: A total of 26 patients with CML-CP managed at MDACC$ D3 ~0 _" O: A+ k
discontinued TKI between 2003 and 2012. The total median follow up time: a1 a4 V6 z8 s1 R1 x2 ~! l
since diagnosis was more than 120 months (mos) (range, 45 mos to 3049 @( g7 o! X! n# D
mos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were) e6 ?& D; @3 q' C
female. All pts had been diagnosed and treated in chronic phase., n+ |; ^9 t$ t9 ~) h
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI
" f7 T0 ?! S6 T; b3 ~as initial therapy (4 received imatinib 400mg/day, 10 imatinib
/ e* \) ] ?- G9 r* F- e9 Q600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with6 a, ^8 I" \- u# d. Q' `
IFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN0 r. K) E, R9 j. Q
failure. Pts treated frontline with TKI started therapy within a median1 j. W c5 E8 d% _0 u
of 0.8 mos from diagnosis (range 0 to 4) and those with previous+ s; F6 C0 @) ~$ K
interferon (n=11) after a median of 60 mos from diagnosis (31 to 1648 b: c7 z6 i- y" d+ J/ t
mos). Before TKI discontinuation 21pts (81%) were receiving their first# P$ m( L; N u3 z0 }8 u" I
TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete+ l% o: Z) ^9 N; w9 H9 n& F2 D
cytogenetic response (CCyR) had been achieved in all 26 pts at a median
1 h9 S, l9 g3 E& `! }of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of
% }$ y, @3 O2 D# Z2 y! I+ I9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All' \1 s8 ?( @- l) w# [
patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)( [, A+ O5 }4 M; V9 [! U, R; {7 z
had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
4 s% J8 K3 Q9 N( T) ^6 Amedian duration of CMR before TKI cessation was 62 mos, (0- 118). The
0 I w9 o" i! g& ~" R/ r8 Amedian duration of total TKI therapy was 101 mos (3- 135).
8 Z& }4 c% h6 f @2 ~" {% x- K. t5 I9 `' I; [+ R
Fourteen pts (54%) discontinued TKI due to adverse events, 2 pts* S( m/ [5 V, {8 ?/ G' J! @9 y# k
discontinued to become pregnant, 5 decided to stop after long CMR, and 5
* S3 C2 n! j, s0 S4 T1 l3 i. }pts discontinued for financial reasons. After TKI discontinuation
& R3 `6 H; D" f# J- Epatients were followed for a median of 11 mos (5-131). Among pts with3 J' o* \, ]; D
CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a4 j6 }9 E% o, U
median of 4 mos (1-11) from discontinuation with median transcript level
( v# F/ d6 j0 y7 [5 y% b/ C7 Nat relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF
8 [+ G9 _6 O; otherapy had CMR at time of TKI discontinuation, 50% of them relapsed.
8 d9 O2 [4 U" y8 p" ?6 i( xAmong 7 pts who discontinued therapy in MMR, after a median follow-up3 O9 U" k: j& i5 o
from discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,8 \* K) n( k& P+ Y7 c$ a% ]
one has minor CyR and one CCyR without retreatment at last follow up/ ^' r/ v+ _2 E! G- Z& C
after 78 and 105 months from TKI discontinuation, and one transformed to
% ~& ?; j/ s* s+ j" N7 x0 k1 ~- Laccelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
9 F; B1 E4 [' k/ Pto MMR. Three pts had a transient molecular recurrence with spontaneous
3 {( k+ Y# }, }" z1 T6 |) E+ o& rre-gain of CMR. Seven pts with relapse were treated again with TKI, 39 v" l z6 Q! m ]
with nilotinib, 2 with dasatinib, and one each with imatinib and- p2 r5 D1 R7 D1 ]/ v* ?0 J7 [3 L
bosutinib (the later in AP). After a median of 13 months on therapy) s! `2 s' }2 |' h8 ]
(range 4-52) all patients improved their response, 5 with CMR and 2 MMR
" e& `. s% r; v# a2 _. W(including the pt that had transformed to AP). There were no deaths or
, [; R* F+ j. e5 @" o# w1 b% ^% Otransformations to blastic phase of CML. At last follow up 14 (54%) pts8 W- i' n: }; e. Z
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and# a6 @3 d2 e7 Z3 W
PCyR.
; g" L: c9 Y+ B( t. C8 L0 W7 S+ b) Z; g$ y' {) v: ^/ {
Conclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular
0 d' v$ C7 }# }- ?+ Jrelapse in nearly half of the pts who discontinue therapy in CMR. Some, `" m3 G9 y9 P
pts who discontinue in MMR may have sustained MMR. Treatment
) d1 m1 a: b$ _1 Jdiscontinuation should be considered experimental and cannot be+ r. G$ Z5 @8 T o! C: C
recommended to pts as a standard approach.4 h, l) y; N, ?- e8 S
! O4 ?; n0 C, G% T& O, l& x8 lDisclosures: Ravandi: BMS: Honoraria, Research Funding. |