MDACC has, for the first time, given their experience of TKI
/ A6 R2 ~- y6 q. d5 W5 e9 Cdiscontinuation. The doctors at MDACC look at 26 patients who8 b ~2 G2 }7 y3 b0 f+ o$ H4 C
discontinued therapy from 2003-2012 for various reasons. These reasons
/ z2 {& R5 L) y$ ?2 e7 H Q3 M. \include long time in CMR, adverse side-effects, pregnancy and financial
8 O S" x' D7 C2 U6 K5 Rconstraints. Please note that 17 patients discontinued therapy in CMR
x* Y1 W6 S: P Z; G2 E, P+ e* cand the rest in MMR. Of the patients in CMR who discontinued therapy,1 @5 {4 r( c5 ~6 O1 h. n6 S" I$ H8 Q- d
47% had molecular relapse. Those in CMR who discontinued and had taken
, c' B; {# ?9 o/ u5 i8 e+ e; Aprior Interferon to a TKI, 50% relapsed. Also note that of these 26/ I1 D+ `* S7 D$ ^& y6 D: ]
patients, most had been treated with high dose Gleevec.
3 v7 O: a: C4 v( y, e
L9 ~( [! A5 z6 K' b% S"All patients discontinued therapy in CML-CP, all in CCyR, of them, 173 j7 w" C8 U. @4 n# ~
(65%) had undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR.; L) Z# t! E) m- @; q1 R% D1 \
The median duration of CMR before TKI cessation was 62 mos, (0- 118).
* ^7 T; C2 _) n! d9 RThe median duration of total TKI therapy was 101 mos (3- 135)."' h( V' D# V9 o1 ?4 `8 {* I
6 t6 r2 E5 U0 Y# P. hTherefore, the median time in CMR before discontinuation was about 57 T) }8 ?7 z6 z% p, |5 A# t- a
years. The median follow-up is only 11 months. The median time for
- @0 @; Z Q/ d$ pmolecular relapse of 8 patients who had been in CMR was 4 months and8 \+ |0 C2 n) b5 S
they relapsed with median PCR value of 0.01 on the International Scale.
& W+ ]4 D) U3 ]4 N' [0 n! ?% F
Of the 7 patients who discontinued when in MMR, 4 remained in MMR at a
' q' b- d7 u8 m% y* C, z/ Vmedian follow-up of 21 months, 1 remained in CCR, 1 in active disease
# I5 m* p6 W6 \: \2 ~0 ~and 1 transformed to accelerated phase off drugs. Therefore, from this
% G( H/ I; j+ c; n9 Q4 d# rdata, scarce as it is, there is a risk of transformation to advanced" o1 G3 e3 C8 u% I6 c
disease if one discontinues drugs in MMR.5 M( S7 R- _2 t: y) ?
( ]* L( P3 J& E* q
2 patients were PCRU (4.5 log machine) and these patients relapsed9 J' z; q3 h" q- p U4 r! z
into MMR when drugs were discontinued.6 B& U' k: @4 u3 @" S: O0 n7 e' _0 M
0 L- u7 F! Z# M4 ~7 ` |Seven pts with relapse were treated again with TKI, 3 with nilotinib,. C! V0 k: U9 g+ _ w$ j8 N
2 with dasatinib, and one each with imatinib and bosutinib (the latter
6 V1 M, D4 s- {7 g: j4 a0 T* rin AP). After a median of 13 months on therapy (range 4-52) all patients
6 G) x( p! W- U& p% r1 Simproved their response, 5 with CMR and 2 MMR (including the pt that had
; o7 S' i% d, O' F$ xtransformed to AP). They do not say why all patients were not retreated- v. t6 m, @* S$ Q* @7 X; R+ f2 p
with imatinib and had to take Nilotinib and Dasatinib. Also, note that
0 H* Z" }! e( Lone did not regain CMR at the 13th month mark though it is good news
/ p4 k( l3 I8 {that 5 did. It may take some time to regain CMR for some who have gone
^; _! T% ^4 b7 _6 G. @% Woff drugs and relapsed. However, from our own list experiences, some( \+ ^# x) {/ e: w# d
had regained CMR fast when they retook the TKI.( U0 C6 P3 |8 r" M8 x
2 G+ R9 M! J4 d' R2 m: f; sThe doctors conclude that treatment discontinuation is experimental
5 K; z3 t# B0 B% ?0 P Q0 u( gand cannot be recommended at this stage as a standard procedure.! g0 @! k- Q# _+ {
7 Q* G- M( Y: |
Best Wishes,
9 c$ }* `; ]4 i3 E! {0 m& c1 `) u1 }( ?! {4 _! v y
Anjana
7 t/ n$ {0 W( T* Z8 w8 t5 F: m
3 ~0 c9 E6 `) Q8 d
$ H6 j8 P. B9 v
; m; O. K! \) I, X5 Q" F! ~
' C8 ]9 G( e% Z1 r. e. v
a6 L4 g( s3 N4 e0 {! B# ?2 }- @
5 C5 b, }2 `: t0 j8 H+ A
- k* M5 |$ C9 @7 O Q$ J6 P6 l. d& e2 J
8 k$ f- j- V6 a3783 Patient (Pt)-Driven Discontinuation of Tyrosine Kinase Inhibitor
# Y" {3 ] c# d7 p& R& M rTheray in Chronic Phase Chronic Myeloid Leukemia (CML) - Single ^1 [5 y. @* }+ a: x% R4 I" j
Institution Experience
9 e6 j$ e) B6 b- J7 r# s7 XProgram: Oral and Poster Abstracts& {4 |4 y) _! g6 i
Session: 632. Chronic Myeloid Leukemia - Therapy: Poster III
: o2 g) `9 }+ |7 a, G( ~ n( R
, C J0 f( V, Y- I) {Monday, December 10, 2012, 6:00 PM-8:00 PM2 O3 c! F, B5 u- F: S9 Y
/ ]9 y- n& W/ w: b# L! H) {
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)
4 S- @1 `% C# V7 Z9 x! `# I- @2 y0 B" J, [6 Z* m3 Z# E8 x; y
Ohad Benjamini, MD1*, Hagop M. Kantarjian, MD1*, Mary Beth Rios, RN1,+ }' n. y" `6 r+ b. U6 B9 v
Elias Jabbour, MD2*, Susan O'Brien, M.D.1, Preetesh Jain, MD, DM, PhD1*,
5 Q4 L+ H j; u! y; h ]Stefan Faderl, MD1, Guillermo Garcia-Manero, MD1*, Farhad Ravandi, MD1,
7 S: i# }1 ^$ O, ~4 JGautam Borthakur, M.D.1, Alfonso Quint醩-Cardama, MD1* and Jorge E.( u; d+ d) ~: `
Cortes, MD1
+ Y3 F1 M( w- ^- S+ |, V6 c) y0 H9 q u# P
1Department of Leukemia, The University of Texas MD Anderson Cancer
7 _1 v+ c/ N$ j; {4 I$ l( OCenter, Houston, TX. z; p$ {9 ?9 }; }& y( }
2Department of Leukemia, The University of Texas M.D. Anderson Cancer* m$ d/ o5 q) z! W# G: P$ |) P
Center, Houston, TX8 U' H/ z, t& n& G
( s8 l8 R$ s% o |: c; ]# ^4 tIntroduction: Some recent studies have reported on the outcome of CML
3 ?+ G, s7 \7 ^$ B; C6 Hpts who discontinued thyrosin kinase inhibitors (TKI) after achieving
' Q: o: v3 v: Q Qsustained undetectable bcr-abl transcript level. Most patients who stop6 {$ @0 }# t/ x2 u# S' K
TKI have experienced molecular relapse. Most patients respond after
# ]: ~: s! p% ]5 P6 Qresuming TKIs regaining undetectable bcr-abl transcript levels. These5 a' }! f- f; j- ?; m( g
series have prospectively planned treatment discontinuation and included0 [* `) [4 c9 Y+ s
only pts that have sustained complete molecular response (CMR) for at
" c1 y4 h0 \# \least 2 yrs. However, in many instances pts may want to discontinue TKIs' f S- _# ]8 Y5 q4 i
not in CMR. Various reasons may lead patients to discontinue TKI4 t7 }+ s6 V/ b0 S
treatment unexpectedly, among them severe adverse effects, pregnancy or; h2 R6 {0 L% s6 z( I) V
economic constraints. This single institution experience reflects the3 E( ~2 q/ k* O2 i3 A4 y# x9 |
heterogeneous nature of pt-driven TKI discontinuation.
G. R; F) Z$ c+ Z8 Q5 s% ^! C3 s" w3 @- K% U
Aim: To characterize the outcome and profile of CML pts who chose to
3 O& s# F1 B. `# U! wdiscontinue TKI therapy in a single center regardless of their initial
# s# x. c8 `) |+ e" o* g- g5 b' Iresponse to TKI therapy.
% f3 B( l& e( p" {+ L( \0 `0 U- M. R' y' H0 l8 ?9 X" z* A
Methods:We retrospectively analyzed MDACC data on all patients with CML" _& N6 b# r. Z6 A- f$ D
that were treated with TKIs in our institution and discontinued therapy.
u" B, B" b: b9 i& ^- c j% t
5 m5 ?: D; G. H4 A, ^Results: A total of 26 patients with CML-CP managed at MDACC/ G) {7 H& X2 p, z, t& ]
discontinued TKI between 2003 and 2012. The total median follow up time9 v1 e: k, W2 ?0 f' j0 k4 x3 ^
since diagnosis was more than 120 months (mos) (range, 45 mos to 304
- v. Q4 ^2 U& T, S2 _2 ]$ h: Jmos). The median age at diagnosis was 48 yrs (range, 28-73); 15 pts were
3 X2 f$ g- q1 T' K3 Gfemale. All pts had been diagnosed and treated in chronic phase. l# L5 P3 O( {7 r1 [# Y
Interferon was initial therapy in 11 pts (42%) and 15 pts received TKI) U2 ]3 M* M0 G; g9 |9 W% x8 d
as initial therapy (4 received imatinib 400mg/day, 10 imatinib3 }+ @9 g3 e( u, w" Z v! U! J( u7 P
600-800mg/day, and 1 bosutinib.) Of the 11 pts initially treated with/ K: n: W' [0 J
IFN, 7 then received imatinib 400mg and 4 imatinib 800mg upon IFN
' e8 k, J( c1 `# ^4 efailure. Pts treated frontline with TKI started therapy within a median
" T d1 K4 A' V8 [5 s$ }" rof 0.8 mos from diagnosis (range 0 to 4) and those with previous. R$ a* B$ J; U- q& C' s
interferon (n=11) after a median of 60 mos from diagnosis (31 to 164
* L- j- j9 t+ i7 V2 kmos). Before TKI discontinuation 21pts (81%) were receiving their first
% y4 k* R* x$ N0 a0 \- D: {" iTKI and 5 (19%) were receiving 2nd (4) or 3rd line (1) TKI. Complete- Q2 `. g. @: K( z
cytogenetic response (CCyR) had been achieved in all 26 pts at a median2 l& I3 p4 E5 \
of 3.5 mos (3-93); Major molecular response (MMR) in all at a median of: D$ V* `' i0 x3 E% I, D
9 mos (3-73) and CMR in 17 (65%) at a median of 22 mos (9-120). All
& t1 @3 C+ N4 d/ j' k* j& cpatients discontinued therapy in CML-CP, all in CCyR, of them, 17 (65%)
1 {, s8 G# h1 }) Xhad undetectable transcripts, 2 (8%) had MR4.5, and 7 (27%) MMR. The
9 S' p4 v; {" ]2 @% {* q- ~median duration of CMR before TKI cessation was 62 mos, (0- 118). The! k7 K8 h" g) M C8 D+ `: ^% N4 A
median duration of total TKI therapy was 101 mos (3- 135).( u2 | |5 X7 r. T
0 y, Y8 q3 }: N3 g* m: h1 r. r9 n
Fourteen pts (54%) discontinued TKI due to adverse events, 2 pts4 q+ |0 L) {& V, K* V) g1 k
discontinued to become pregnant, 5 decided to stop after long CMR, and 50 E6 r* q" V$ O& K
pts discontinued for financial reasons. After TKI discontinuation
9 Y) Q0 N2 ^( A) [- ypatients were followed for a median of 11 mos (5-131). Among pts with" S; |# {9 W/ q# F# |7 S: T& B& o
CMR at discontinuation, molecular relapse occurred in 8 (47%) pts at a* i4 G5 s& Z. W' n0 q' V
median of 4 mos (1-11) from discontinuation with median transcript level$ [4 `" z. Q5 O& v. P8 U
at relapse of 0.07 (IS) (range, 0.004-2.17). Six pts with initial INF n6 i6 f. t* Q8 w, b% q6 D3 n
therapy had CMR at time of TKI discontinuation, 50% of them relapsed.
; Q9 P; ~/ a& E& |Among 7 pts who discontinued therapy in MMR, after a median follow-up; _4 V, Z! _. p, J- a& T+ `
from discontinuation of 21.6 months (range, 4.6-106), 4 remained at MMR,
. J4 O# f& M2 @/ S1 a* v" D" ?one has minor CyR and one CCyR without retreatment at last follow up/ l- ~$ N# q7 ~/ h, g# W
after 78 and 105 months from TKI discontinuation, and one transformed to) z2 k: K2 U& S) N" S& O2 N
accelerated phase (AP). The 2 pts with MR4.5at discontinuation relapsed1 ?4 ?: Y+ H- k8 [
to MMR. Three pts had a transient molecular recurrence with spontaneous' b* l+ `/ m$ f' Y! ?, ?9 ]
re-gain of CMR. Seven pts with relapse were treated again with TKI, 3
2 @. U# |9 k& w* m3 F4 uwith nilotinib, 2 with dasatinib, and one each with imatinib and9 a9 E6 g( @; _
bosutinib (the later in AP). After a median of 13 months on therapy& p5 O4 m, E$ S5 ^! e8 g3 n3 `* H3 `
(range 4-52) all patients improved their response, 5 with CMR and 2 MMR
! O* y* c# r/ g Z* Q(including the pt that had transformed to AP). There were no deaths or
! k3 T% M$ ]! t2 \. O" ~( e# ~6 Htransformations to blastic phase of CML. At last follow up 14 (54%) pts+ P/ o& ~; o2 e4 `" ?1 x
were in CMR, 5 (19%) in MMR,5 (19%) in CCyR and 1 each in minor CyR and
" B8 V: Q; Z sPCyR.
( T/ e( k/ v8 ^6 \+ K; P6 \( M8 ?, V! R
Conclusion: Pt-driven TKI discontinuation in CML-CP leads to molecular6 m4 `) f2 X) G7 b! M5 p L- ]% O
relapse in nearly half of the pts who discontinue therapy in CMR. Some
4 |3 k# p/ w" h: L* t0 Ppts who discontinue in MMR may have sustained MMR. Treatment
! `/ K/ ^2 m+ k# |& E7 O: s+ Pdiscontinuation should be considered experimental and cannot be
1 E) z' B$ K) H* s! f: rrecommended to pts as a standard approach.
9 t1 s: [) u( I% c! a
' x q6 n2 q4 A( mDisclosures: Ravandi: BMS: Honoraria, Research Funding. |