MDACC has, for the first time, given their experience of TKI5 f& |& I2 o" h5 Z5 j. v" V) l1 x
discontinuation. The doctors at MDACC look at 26 patients who
' r, T$ d+ k `& ^) idiscontinued therapy from 2003-2012 for various reasons. These reasons S# m4 l/ |8 a# F
include long time in CMR, adverse side-effects, pregnancy and financial- g X% @$ d; D; m) b
constraints. Please note that 17 patients discontinued therapy in CMR
% U: M9 C/ ^5 z( u& }and the rest in MMR. Of the patients in CMR who discontinued therapy,
7 a }4 ~( n1 O0 f47% had molecular relapse. Those in CMR who discontinued and had taken
& o3 Y* i F; m& hprior Interferon to a TKI, 50% relapsed. Also note that of these 260 Q$ }, ^ e! E, C1 }8 l% V
patients, most had been treated with high dose Gleevec.
! m; x6 c) F, \; h) k
5 ]% [' A# u$ u, g5 f9 A"All patients discontinued therapy in CML-CP, all in CCyR, of them, 17& N6 O. a: ?/ _
(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.
$ ~; J5 X# F7 L- O- p1 BThe median duration of CMR before TKI cessation was 62 mos, (0- 118).
& v& s; c& ?2 Z3 K; uThe median duration of total TKI therapy was 101 mos (3- 135)."2 |# @- i" T/ B |/ ]
8 [5 _+ i0 ^- |. W* a V- a3 h
Therefore, the median time in CMR before discontinuation was about 5
3 D% E; d% ~* Z j2 v2 a! }years. The median follow-up is only 11 months. The median time for
z U1 k4 v0 a$ H" P% ~; Smolecular relapse of 8 patients who had been in CMR was 4 months and: C$ U4 F3 X% U
they relapsed with median PCR value of 0.01 on the International Scale.
0 l H% O5 L0 E R# W) N7 r, j
# w) m1 t/ Y, k6 R. ^) _) WOf the 7 patients who discontinued when in MMR, 4 remained in MMR at a
* n1 }# z5 f6 hmedian follow-up of 21 months, 1 remained in CCR, 1 in active disease' I! h" m) ?1 U6 g" j% U) n( G
and 1 transformed to accelerated phase off drugs. Therefore, from this
$ h0 B4 k8 V# O. Zdata, scarce as it is, there is a risk of transformation to advanced
; |3 I2 Y X; f0 w3 t2 q1 [disease if one discontinues drugs in MMR.
6 v9 E& g8 f' R) m" ~5 f
' V" |( G d& E. x% x2 patients were PCRU (4.5 log machine) and these patients relapsed
7 @6 b5 Q0 L9 Z! W3 Rinto MMR when drugs were discontinued.
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Seven pts with relapse were treated again with TKI, 3 with nilotinib,0 c! R8 E& }6 P: U5 |2 j
2 with dasatinib, and one each with imatinib and bosutinib (the latter3 T3 r- S6 j9 k' m6 z% T
in AP). After a median of 13 months on therapy (range 4-52) all patients2 G8 W* |% `$ m( q
improved their response, 5 with CMR and 2 MMR (including the pt that had4 k3 b7 s7 m {( p& C8 d9 D
transformed to AP). They do not say why all patients were not retreated
7 H, g% W1 x5 l7 \+ `# w/ `0 B& b* |with imatinib and had to take Nilotinib and Dasatinib. Also, note that0 E6 I, v1 t' Y! k6 t; X) ]
one did not regain CMR at the 13th month mark though it is good news' U, N1 U- T; r5 ~- X
that 5 did. It may take some time to regain CMR for some who have gone
# x* ^" ^- a- t; J* l0 g# Foff drugs and relapsed. However, from our own list experiences, some
! ~7 z ?- m1 B0 t7 S. Xhad regained CMR fast when they retook the TKI.) S3 R6 {* J; r2 I+ O
# r. v0 s. @9 k0 {% X" v
The doctors conclude that treatment discontinuation is experimental
|; d% `8 l% S5 Q. c$ c/ ]and cannot be recommended at this stage as a standard procedure.
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& a. t% ^- d6 z, L7 q% l0 nBest Wishes,. ~) Y% R9 S5 c# A: p0 W" M
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Anjana6 g& |6 E& F- |+ h2 d( v
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" y' F( |4 U% E! S, h+ E4 }! T& o3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor2 q6 R# c: H. z
Theray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single( D) w. G: h2 Y4 C" P
Institution Experience
+ W* V6 ~7 x; r( t" {& RProgram: Oral and Poster Abstracts. d0 t1 k+ d [. Q% e$ I+ k: V
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III
8 _2 d& D0 o, K$ P! M! m) ~8 O: P' C
/ \; F9 G/ d1 |6 q, w/ M' Y0 QMonday, December 10, 2012, 6:00 PM-8:00 PM1 r: }0 ^9 \1 o ?( z3 F
9 M1 n3 Q9 S/ B2 k `
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)9 c# D# R( a1 Q N5 c% i
3 a' l: i2 a0 b' q) s/ qOhad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,
6 e; Y& d; W0 i9 |Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
4 n' {# G7 r6 {1 hStefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,
$ a1 w) }3 m( I0 D' r! AGautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.7 C# R" @: h) R* G$ {
Cortes, MD1
! d9 W9 n! p1 w p( U) P
$ ?7 R: @1 s9 w6 C. w% \1Department of Leukemia, The University of Texas MD Anderson Cancer
, l9 k; H' c* H6 M$ ?Center, Houston, TX5 ]- d) E. t; Q- p5 v% d
2Department of Leukemia, The University of Texas M.D. Anderson Cancer5 e* Y7 a4 I1 d; f0 {
Center, Houston, TX% T8 A' |3 M' J1 }2 J
1 }- R) W/ m. Y R8 d
Introduction: Some recent studies have reported on the outcome of CML
- X" g/ P- p) q6 K7 v6 S) a$ opts who discontinued thyrosin kinase inhibitors (TKI) after achieving
9 V+ t: n' T9 Ssustained undetectable bcr-abl transcript level. Most patients who stop+ M5 n$ }, r% O4 v/ B3 C! K
TKI have experienced molecular relapse. Most patients respond after& l4 o5 X2 B: i% l2 `/ X
resuming TKIs regaining undetectable bcr-abl transcript levels. These
B# ~$ S3 S$ l }, lseries have prospectively planned treatment discontinuation and included4 Y* Z8 f1 Z) z! X
only pts that have sustained complete molecular response (CMR) for at
0 z' ]; N2 f# @7 S7 e. |( wleast 2 yrs. However, in many instances pts may want to discontinue TKIs
+ v4 y. C& u! I4 }not in CMR. Various reasons may lead patients to discontinue TKI* y; b" a0 x; q' K' Q3 v8 U; J5 G
treatment unexpectedly, among them severe adverse effects, pregnancy or _. s. g! q* @2 Q- \1 F5 l+ X! W2 b' d
economic constraints. This single institution experience reflects the
, |% |- |8 c" I* L6 z* B8 @! d( p) Uheterogeneous nature of pt-driven TKI discontinuation.
* V# i) O$ `3 N/ \% H: r' k5 G/ ~ D7 P" Z7 E; L% R& h
Aim: To characterize the outcome and profile of CML pts who chose to
3 Z. m' a9 @% f# g4 |0 ndiscontinue TKI therapy in a single center regardless of their initial
& A! p4 r. w, T9 b4 Oresponse to TKI therapy./ @9 J9 ^( {& @0 \0 V# {9 ?
: ]1 F8 r( F1 S
Methods:We retrospectively analyzed MDACC data on all patients with CML# X) O# \0 X9 f/ t5 I5 a
that were treated with TKIs in our institution and discontinued therapy.$ W$ W4 L) F+ j4 `, E: r4 ^9 D" D" U! {
/ V& g- R% J% R3 B
Results: A total of 26 patients with CML-CP managed at MDACC: i% \5 ~ s+ x- H) @9 K1 ~, }3 P
discontinued TKI between 2003 and 2012. The total median follow up time: b O+ X6 M2 g5 m+ O5 @
since diagnosis was more than 120 months (mos) (range, 45 mos to 304! V- q* A3 ]: q8 V% P
mos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
6 E; }& l; g5 s5 V$ Afemale. All pts had been diagnosed and treated in chronic phase.. [( M# B: N+ V x/ E& G
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI* A* L% Y; y2 f# C* S
as initial therapy (4 received imatinib 400mg/day, 10 imatinib4 P! j4 O" ^" L6 O% a8 ?( M
600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with
/ V) l7 W& `: [. y5 ]( PIFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN
$ b; L' O+ `5 Gfailure. Pts treated frontline with TKI started therapy within a median" v/ y8 F0 o4 ~7 O: F0 j: u# Z
of 0.8 mos from diagnosis (range 0 to 4) and those with previous2 Q. M' m! J$ \0 L$ f
interferon (n=11) after a median of 60 mos from diagnosis (31 to 164
! t6 {- T: h- v4 n1 z. J. V3 rmos). Before TKI discontinuation 21pts (81%) were receiving their first( T0 m6 d, H3 w( b- u1 D
TKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete3 m, @6 k7 q; x, ?; \9 ~
cytogenetic response (CCyR) had been achieved in all 26 pts at a median) z, I1 I1 `) F. N( X
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of
& ^' `- Y1 S) w: ^5 S, u7 F9 U7 L4 \' z9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All
: d9 P& \6 h3 b3 F L$ \patients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)
9 K p# b' T' [had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The/ N# _" b, q6 `' q0 B0 M
median duration of CMR before TKI cessation was 62 mos, (0- 118). The
0 l3 I* k4 k C" V% S- `+ Jmedian duration of total TKI therapy was 101 mos (3- 135).
2 T" O- Y0 M# s7 y# T7 j' i' E3 f: G @ V
Fourteen pts (54%) discontinued TKI due to adverse events, 2 pts) e9 l) x* H% C7 c2 O" O
discontinued to become pregnant, 5 decided to stop after long CMR, and 5
3 X( f; ~1 {1 y4 l0 R* b9 g8 xpts discontinued for financial reasons. After TKI discontinuation
6 N" | r9 `6 Y( N, W2 ypatients were followed for a median of 11 mos (5-131). Among pts with
* }/ d' n* `% aCMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a3 l, S3 L* @! A- ~. x
median of 4 mos (1-11) from discontinuation with median transcript level
! }1 S/ K9 X9 R0 z4 B% vat relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF& D' N m K# ~, k) e8 F1 I
therapy had CMR at time of TKI discontinuation, 50% of them relapsed.8 m) Y2 ~; ?; \5 f2 y1 ~
Among 7 pts who discontinued therapy in MMR, after a median follow-up
7 W# Z# W& d) O: g8 D' Z$ c6 Jfrom discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
% ?6 n3 _2 Y! t- Y* M4 z# h1 V! Sone has minor CyR and one CCyR without retreatment at last follow up
' b i( g O, ` y5 e8 o7 {( _after 78 and 105 months from TKI discontinuation, and one transformed to
/ ]$ ?7 W5 N% J2 Y" ?accelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed, |8 @" l) H- U3 H M: G! g' v1 Z
to MMR. Three pts had a transient molecular recurrence with spontaneous
3 T, x$ a& I; nre-gain of CMR. Seven pts with relapse were treated again with TKI, 3
W0 H9 q0 Z; Gwith nilotinib, 2 with dasatinib, and one each with imatinib and
# Q7 P, ^6 Q \9 |" D2 ?7 Ubosutinib (the later in AP). After a median of 13 months on therapy
/ W" H! X/ E; |/ ?/ ~( `+ v" w! h(range 4-52) all patients improved their response, 5 with CMR and 2 MMR( X/ S5 S5 R! m: p# J3 T1 P Q0 T/ a
(including the pt that had transformed to AP). There were no deaths or
7 H; R/ Q6 L1 Y g5 X" Itransformations to blastic phase of CML. At last follow up 14 (54%) pts# l8 L5 l0 O* G# c
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and' g5 f! E5 T1 i0 \) ^0 x9 x9 @
PCyR.: X1 A& b2 C$ x0 `3 K' a
$ p% Y) b+ ~7 @" G8 x- x, ?Conclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular
8 q# J( G" |& L$ G9 G; U+ F" S& srelapse in nearly half of the pts who discontinue therapy in CMR. Some( ^6 V1 j$ e, ]1 K
pts who discontinue in MMR may have sustained MMR. Treatment
U `8 G8 h7 j" V. g+ Ldiscontinuation should be considered experimental and cannot be$ S k8 f) ?& W5 o
recommended to pts as a standard approach.
" r3 B; p5 L5 ]6 k3 d+ L( s
4 ^0 T1 r& ]' J B0 z$ ?8 c3 JDisclosures: Ravandi: BMS: Honoraria, Research Funding. |