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