MDACC has, for the first time, given their experience of TKI
9 G1 U8 D4 H2 M0 A7 R& ydiscontinuation. The doctors at MDACC look at 26 patients who
) U, U, q. |9 {9 z1 a( idiscontinued therapy from 2003-2012 for various reasons. These reasons4 j; u9 E& g% @% L. w. H
include long time in CMR, adverse side-effects, pregnancy and financial `5 K# c$ W% O2 X; o
constraints. Please note that 17 patients discontinued therapy in CMR
5 p7 H p+ J; N; [8 w" r: ]0 eand the rest in MMR. Of the patients in CMR who discontinued therapy,
) c. S" V2 c6 f# S% O/ c% G ~47% had molecular relapse. Those in CMR who discontinued and had taken2 a \/ @& x2 S+ i0 [
prior Interferon to a TKI, 50% relapsed. Also note that of these 26& U; q( F6 @0 n: u: Q
patients, most had been treated with high dose Gleevec.
+ Q' Q& K5 v- Y% c: h7 k- q9 M' [! D b
"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17& {5 r9 \5 f7 c% E. d+ @1 Z2 `
(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.
& @2 F( ~! X/ R/ P8 o- eThe median duration of CMR before TKI cessation was 62 mos, (0- 118).8 R1 y& b5 b5 F) l1 s% s2 V
The median duration of total TKI therapy was 101 mos (3- 135)."1 M o# F8 o0 }9 ?% W
1 W# u7 h4 \: ~* y7 B' v( d5 |Therefore, the median time in CMR before discontinuation was about 5% r! Y: u; @! \+ E) b) r
years. The median follow-up is only 11 months. The median time for/ z% Y" ?3 @0 M( \
molecular relapse of 8 patients who had been in CMR was 4 months and: t9 C& ?% _3 |' a: {- e' N- a$ l
they relapsed with median PCR value of 0.01 on the International Scale.
" F: O: A/ X% R. z. t W. A5 X: x7 A; e
Of the 7 patients who discontinued when in MMR, 4 remained in MMR at a/ e+ p8 H) `5 c" W. N: O
median follow-up of 21 months, 1 remained in CCR, 1 in active disease, d+ C3 p6 V5 v L. G$ \( @! C
and 1 transformed to accelerated phase off drugs. Therefore, from this$ w' I( F6 K. {* }
data, scarce as it is, there is a risk of transformation to advanced: T( [" r+ v! |
disease if one discontinues drugs in MMR.: c: W* \! ]( ?" i) Z/ i
4 f. Y9 m4 l. l6 Q# [$ U4 {8 m
2 patients were PCRU (4.5 log machine) and these patients relapsed, ^9 A1 u" Z1 w J: j
into MMR when drugs were discontinued.
5 @6 E# o& {! A" {* I) s3 }
, Z- t+ i5 m7 i D2 DSeven pts with relapse were treated again with TKI, 3 with nilotinib,; y: E0 Z' t" R/ z& ?9 L
2 with dasatinib, and one each with imatinib and bosutinib (the latter
2 U# L$ P/ t6 H u. C! Q4 gin AP). After a median of 13 months on therapy (range 4-52) all patients
2 g# r9 a4 W; N: Z% j, @improved their response, 5 with CMR and 2 MMR (including the pt that had
$ ^' c! O; y# U9 N) A' Qtransformed to AP). They do not say why all patients were not retreated9 E# T. J& [: t' J# I5 _
with imatinib and had to take Nilotinib and Dasatinib. Also, note that2 z7 O$ \/ _! N; d) [
one did not regain CMR at the 13th month mark though it is good news
0 q& ?5 {6 q6 m3 z! Mthat 5 did. It may take some time to regain CMR for some who have gone
+ v9 M9 b6 }7 n/ z1 ?off drugs and relapsed. However, from our own list experiences, some# H0 A9 @7 p8 d3 I
had regained CMR fast when they retook the TKI.
# f7 U! r O+ [9 ^+ e; F( c: V' ?/ n6 B' F
The doctors conclude that treatment discontinuation is experimental
& x/ H1 \- K- R; n# d& Q" l$ ^and cannot be recommended at this stage as a standard procedure.
$ s. O2 A* z, Z* S4 ^9 o
/ z2 J4 _. ?$ \- wBest Wishes,
) |+ n: I. D! @" o, s* F: Q2 |) F8 ~+ Q1 `- i; p. m6 M
Anjana
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3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor) c9 V) @! b- V: A, b/ m+ v
Theray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single
# D. t! t+ H* n! x( N7 wInstitution Experience
# J* E* P) d1 R& p) BProgram: Oral and Poster Abstracts5 K0 l- S5 @# F8 N0 h, O
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III
6 `1 v# P$ u3 P3 U! \5 a+ @8 t5 Z) t; s# E3 U" I
Monday, December 10, 2012, 6:00 PM-8:00 PM
; }8 N1 b3 d7 s' x) V; D Z2 O. ]
; N4 V( W7 C% DHall B1-B2, Level 1, Building B (Georgia World Congress Center)' K) \- {6 x' a \/ h; ^; x0 ~0 e" ]
6 o$ G$ J2 G1 I z. d$ m6 A$ [" _
Ohad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,! `) U: V! P' T; g5 B
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
" w/ z0 C; V" Z5 ~6 q5 [Stefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,4 B& `( ]& d% q* R
Gautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.) t2 u" `) O# H2 J7 i. s
Cortes, MD1
5 v9 D$ ]0 a7 `4 L, B% `; }# b6 w% t) d' h5 y
1Department of Leukemia, The University of Texas MD Anderson Cancer
5 G2 P; u+ F% H- JCenter, Houston, TX
4 ? K" p& z3 m- ^2Department of Leukemia, The University of Texas M.D. Anderson Cancer
) |* A1 p+ {3 V1 p0 c& \* ~, s( u6 OCenter, Houston, TX- a1 `9 m3 ^3 @8 H9 I- H
$ C* I9 F; X' y4 L% Z7 v1 D
Introduction: Some recent studies have reported on the outcome of CML
8 ^: w/ I: C) o! Q6 Q/ Ypts who discontinued thyrosin kinase inhibitors (TKI) after achieving
1 y8 s8 j2 o1 V7 |$ _5 `! U6 @sustained undetectable bcr-abl transcript level. Most patients who stop- {5 U1 x, o2 @. s
TKI have experienced molecular relapse. Most patients respond after6 f. Z) Z+ R I
resuming TKIs regaining undetectable bcr-abl transcript levels. These1 l% V0 x0 [4 N5 ]7 G; g
series have prospectively planned treatment discontinuation and included
% |6 }0 _* y5 G4 s/ uonly pts that have sustained complete molecular response (CMR) for at9 O, F2 }0 M& z. G" j% B
least 2 yrs. However, in many instances pts may want to discontinue TKIs) V4 s/ I) C" r( J7 J: K0 E5 L
not in CMR. Various reasons may lead patients to discontinue TKI! Q2 _" H! a2 L* B
treatment unexpectedly, among them severe adverse effects, pregnancy or6 Y/ p1 f; ~4 i
economic constraints. This single institution experience reflects the
: h% {0 l0 ]+ o" jheterogeneous nature of pt-driven TKI discontinuation. }# S. l' v' N. u2 T
) q1 Z- V; @ \* SAim: To characterize the outcome and profile of CML pts who chose to; A3 @+ d- R! |4 i( Z
discontinue TKI therapy in a single center regardless of their initial, t: y, r" k i* I6 V/ }, \
response to TKI therapy.+ i7 e3 Q+ X; A1 S1 G
4 z7 k! J6 ?0 C8 \1 H l
Methods:We retrospectively analyzed MDACC data on all patients with CML
, e* \8 q6 z. ythat were treated with TKIs in our institution and discontinued therapy.! k- n* D7 n- m
$ l) c2 l8 V. P% `+ yResults: A total of 26 patients with CML-CP managed at MDACC
0 l9 P! z$ V: [% Z; b0 ]# W' W. rdiscontinued TKI between 2003 and 2012. The total median follow up time
; y* l& i9 r9 K/ qsince diagnosis was more than 120 months (mos) (range, 45 mos to 3044 }2 }5 F7 P2 U; k3 _* {
mos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were# `2 I! u2 _- e6 F
female. All pts had been diagnosed and treated in chronic phase.+ {* b( {3 ?. Z: g" ]* Q
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI
/ s1 y+ w$ w3 A, ^as initial therapy (4 received imatinib 400mg/day, 10 imatinib6 T7 A8 O% H, T
600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with
; z0 G' m* [, s4 x) y$ \* U5 J- l0 JIFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN9 R! `: d3 P6 o
failure. Pts treated frontline with TKI started therapy within a median& N9 I, F1 N. a, U3 h
of 0.8 mos from diagnosis (range 0 to 4) and those with previous, ?- p* }5 q1 ^; ]% y! s
interferon (n=11) after a median of 60 mos from diagnosis (31 to 164" ~7 u+ D0 P1 m, H$ \
mos). Before TKI discontinuation 21pts (81%) were receiving their first
3 ]5 `$ P5 c8 L' ~4 KTKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete7 {( q$ O( ]3 Y' m1 f
cytogenetic response (CCyR) had been achieved in all 26 pts at a median( A" N) m, G# `4 R% G- F9 ~
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of
, P( |/ \$ \9 _/ d3 H9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All0 K7 U' U4 E( t' r+ n
patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)0 ~" S1 s% A* M2 S- q3 j
had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The1 } t- T# I) D) q/ p9 L
median duration of CMR before TKI cessation was 62 mos, (0- 118). The, a3 ?! n `( t( Q/ F. g" J$ a! y
median duration of total TKI therapy was 101 mos (3- 135).
4 y8 E' `8 o7 c1 h( c5 ~. y6 C3 V% Q0 n! Y& C
Fourteen pts (54%) discontinued TKI due to adverse events, 2 pts
6 g+ [% d1 ?* ]5 Bdiscontinued to become pregnant, 5 decided to stop after long CMR, and 5
/ m \- }* R0 n* Z( k. opts discontinued for financial reasons. After TKI discontinuation5 R: D1 m6 |# s0 g
patients were followed for a median of 11 mos (5-131). Among pts with. \0 p: a7 U9 w) }3 s; I2 E1 v
CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a% t. {$ Z3 r/ y9 C3 M8 Z$ V3 V
median of 4 mos (1-11) from discontinuation with median transcript level
/ h5 _7 Q4 ^" e& Eat relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF
# Z, i( q7 p5 Q, C( j- Itherapy had CMR at time of TKI discontinuation, 50% of them relapsed.2 _, X1 C0 R- W) |+ u
Among 7 pts who discontinued therapy in MMR, after a median follow-up- X( G0 f- @- O% q/ P" Y+ N. p; k
from discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
+ l3 v" }, R+ f! P" f& Kone has minor CyR and one CCyR without retreatment at last follow up* ^! P1 h: K9 e3 z6 F$ k
after 78 and 105 months from TKI discontinuation, and one transformed to
+ P8 E0 j2 L# H7 g; Faccelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed
2 v9 F0 F# P6 V. J, y0 Eto MMR. Three pts had a transient molecular recurrence with spontaneous5 a* m' h! N6 n% j6 `! a
re-gain of CMR. Seven pts with relapse were treated again with TKI, 3
3 L& w+ ]4 z/ q G. iwith nilotinib, 2 with dasatinib, and one each with imatinib and
' q& s, Q& s9 y& p3 obosutinib (the later in AP). After a median of 13 months on therapy; u$ O: q- z/ I; l
(range 4-52) all patients improved their response, 5 with CMR and 2 MMR
* ^8 `& f6 P; R6 g(including the pt that had transformed to AP). There were no deaths or. y5 `% K: d7 X7 i- v; c
transformations to blastic phase of CML. At last follow up 14 (54%) pts
+ ]) e' e8 J+ |+ a$ i* N9 O( q! gwere in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
1 d4 D& m) e0 l* L2 IPCyR. [, Q; Y; e& Q5 D
3 u# c0 y' j0 ~9 @7 R
Conclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular- _, M2 x" z( y1 }9 g; ~3 U8 I! w
relapse in nearly half of the pts who discontinue therapy in CMR. Some4 H' [! F' T ]/ V! P
pts who discontinue in MMR may have sustained MMR. Treatment
$ G2 P6 q% }6 udiscontinuation should be considered experimental and cannot be& T: `4 d4 c* Y; j, X, q
recommended to pts as a standard approach.4 A, Z4 d: R) ]% h' u# L" K& Y
4 @* S* n# b2 \" r' [" F
Disclosures: Ravandi: BMS: Honoraria, Research Funding. |