mantle cell lymphoma: a tortoise and the hare · 2019-03-26 · tortoise and the hare. mantle cell...
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Alvaro Alencar
II Simpósio Internacional de Onco-HematologiaMarch 22, 2019Sao Paulo, Brazil
Mantle cell lymphoma: a tortoise and the hare
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Mantle cell lymphoma
Most patients need therapy Few with indolent leukemic presentation
Prognostic value
Ki67, SOX-11, TP53
Fit for intensive therapy?
R + something induction followed by ASCT and maintenance
R + intensive therapy with no ASCT but maintenance
R + something followed by maintenance
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SWOG 1106
Br J Haematol 176:759, 2017
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SWOG 1106
Br J Haematol 176:759, 2017
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SWOG 1106 – 2-yr PFS
Br J Haematol 176:759, 2017
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SWOG 1106 – 2 yr OS
Br J Haematol 176:759, 2017
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SWOG 1106 - responses
ORR 94·1% (RH) vs 82·9% (BR) (p = 0·4)
CR 40% (RH) vs 35% (BR)
PR 43% (RH) vs 59% (BR)
MRD via NGS
12 pre and post induction paired specimens (2 RH, 10 BR)
RH
b/l - 2 MRD (+)
EOI - 2 MRD (-)
BR
b/l - 1 MRD (-), 9 MRD (+)
EOI - 7 MRD (-), 2 MRD (+)
Br J Haematol 176:759, 2017
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Alliance 41202
BR vs ibrutinib vs ibrutinib + rituximab
N Engl J Med 379:2517, 2018
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Bortezomib
J Clin Oncol 24:4867, 2006; Ann Oncol 20:520, 2009
Study n Tx lines Median F/U
ORR PFS OS
PINNACLE(R/R MCL)
155 median 4 26.4 mos32%
8% CR6.5 mos 23.5 mos
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Bortezomib + CIT
Lancet Oncol 19:1449, 2018; N Engl J Med 372:944, 2015; Leuk Lymphoma 59:896, 2018; Haematologica 104:138, 2019Blood 117:2807, 2011; Leuk Lymphoma 56:958, 2015; J Clin Oncol epub Feb 27 2019; Blood 123:2944, 2014
Study n Pop Median F/U
ORR PFS OS
LYM-3002(VR-CAP vs R-CHOP)
268
1L, non-tx
82 mos 92 vs 89%
53% v 42% CR
65% CR (tx-el)
24.7 mos vs 14.4 mos (p<0.001)
32.6 mos(tx-eligible)
90.7 vs 55.7 mos
(p=0.001)
487 40 mos -
+ BR 74 1L 52 mos86.5%
78% PET CR(41/54 MRD-)
70.3% @2 yrs
57.6% @4 yrs
86.6% MRD-
28.6% MRD+
+ BR 7 R/R 27 mos 71% 47% @ 2 yrs
+ lenalidomide 53 R/R 46 mos40%
15% CR40% 1-yr 68% 1-yr
BRIGHTORR 97% / 40% CR
5-yr PFS 65.5%mPFS ~50 mosmOS not reached
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Lenalidomide
Lancet Oncol 17:319, 2016; Br J Haematol 180:224, 2018; Ann Oncol 24:2892, 2013; J Clin Oncol 31:3688, 2013
Study n Tx lines Median F/U
ORR PFS OS
SPRINT/MCL-002(vs investig choice)
254(2:1)
median 2 15.9 mos40%
5% CR8.7 mos 27.9 mos
NHL-003(R/R MCL)
57 median 3 31.8 mos35%
12% CR8.8 mos NR
EMERGE/MCL-001(p bortezomib)
134 median 4 9.9 mos28%
7.5% CR4 mos 19 mos
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Lenalidomide + something
Haematologica 102:e203, 2017; Leuk Lymphoma 56:958, 2015; Lancet Oncol 13:716, 2012
Study n Tx lines Median F/U
ORR PFS OS
FIL(+ BR in 2L)
42 - 29 mos88%
44% CR20 mos NR
CALGB 50501(+ bortezomib)
53 median 1 46 mos40%
15% CR40% 1-yr 68% 1-yr
+ rituxan 44 median 2 23.1 mos57%
36% CR11.1 mos 24.3 mos
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Lenalidomide + rituximab
N Engl J Med 373; 1835, 2015;
Study n Tx line Median F/U
ORR PFS OS
+ rituxan 38 1L
30 mos92%
64% CR80% @ 3 yrs 90% @ 3 yrs
64 mos8/10 MRD-
(p 3y tx)
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Ibrutinib
Haematol epub Nov 15 2018; Br J Haematol 179:430, 2017; N Engl J Med 369:507, 2013; Blood 124:4471, 2014;Lancet 387:770, 2016; Leukemia 32:1799, 2018;
Study n Tx lines Median F/U
ORR PFS OS
PCYC-1104(R/R MCL)
37073.2%
>2 lines41.4 mos
69.7%27% CR
77.8% (2L)37% CR
12.5 mos
25.4 mos (2L)
26.7 mos
NR (2L)
SPARK(p bortezomib)
RAY(vs Temsirolimus)
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Ibrutinib + biologic
Blood 133:1201, 2019; Lancet Oncol 17:48, 2016; Br J Haematol 182:404, 2018; N Engl J Med 378:1211, 2018
Study n Tx lines Median F/U
ORR PFS OS
+ palbociclib 27 median 1 25.6 mos67%
27% CR59.4% 2-yr 60.6% 2-yr
+ rituximab 50 median 3 47 mos88%
58% CR43 mos
mOS NR69% 3-yr
+ venetoclax 24 median 2 15.9 mos71%
62% CRmPFS NR
75% @ 12mos79%
@12 mos
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SWOG 1106 – 5-yr F/U
ORR 94·1% (RH) vs 85·7% (BR) (p = 0·4)
CR 41% (RH) vs 43% (BR)
ASH 2018 abstr 1593
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IFM 2009 – RVD +/- ASCT
N Engl J Med 376:1311, 2017
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Conclusion
New agents expanding treatment options
Chemoimmunotherapy paradigm remains
ASCT should still be considered
Maintenance therapy should still be considered
Early introduction of biologic agents
Evolution of MRD analysis