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
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
SWOG 1106
Br J Haematol 176:759, 2017
SWOG 1106
Br J Haematol 176:759, 2017
SWOG 1106 – 2-yr PFS
Br J Haematol 176:759, 2017
SWOG 1106 – 2 yr OS
Br J Haematol 176:759, 2017
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
Alliance 41202
BR vs ibrutinib vs ibrutinib + rituximab
N Engl J Med 379:2517, 2018
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
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
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
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
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)
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)
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
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
IFM 2009 – RVD +/- ASCT
N Engl J Med 376:1311, 2017
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
Thank You
aalencar@med.miami.edu
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