Case-Based Workshop With the Experts: Evolving Management Strategies in Non-Hodgkin’s Lymphoma This program is supported by educational grants from

Case-Based Workshop With the Experts: Evolving Management Strategies in Non-Hodgkin’s Lymphoma

This program is supported by educational grants from

Owen A. O’Connor, MD, PhDProfessor of Medicine and Pharmacology Deputy Director for Clinical Research and Cancer Treatment NYU Cancer Institute Chief, Division of Hematologic Malignancies and Medical Oncology NYU Langone Medical Center New York, New York

Multidisciplinary Approaches for the Diagnosis and Optimal Treatment of MCL

clinicaloptions.com/oncologyEvolving Management Strategies in Non-Hodgkin’s Lymphoma

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Program Faculty

Program DirectorMary Jo Lechowicz, MDAssistant Professor Hematology/OncologyEmory UniversityAtlanta, Georgia

Core FacultyChristopher R. Flowers, MD, MSDirector, Lymphoma ProgramMedical Director, Oncology Data CenterAssistant ProfessorBone Marrow and Stem Cell TransplantationDepartment of Hematology and OncologyEmory UniversityAtlanta, Georgia

Owen A. O’Connor, MD, PhDProfessor of Medicine and Pharmacology Deputy Director for Clinical Research and Cancer Treatment NYU Cancer Institute Chief, Division of Hematologic Malignancies and Medical Oncology NYU Langone Medical Center New York, New York

Julie M. Vose, MDNeumann M. and Mildred E. Harris ProfessorChief, Section of Hematology/ OncologyProfessor of MedicineUniversity of Nebraska Medical CenterOmaha, Nebraska


Faculty Disclosures

Christopher R. Flowers, MD, MS, has disclosed that he has received consulting fees from Celgene and Prescription Solutions and research funding from Millennium, Pfizer, and Spectrum. He has also disclosed that he has other (nonpaying advisory boards) relationships with Biogen Idec and Genentech.

Mary Jo Lechowicz, MD, has no significant financial relationships to disclose.

Owen A. O’Connor, MD, PhD, has disclosed that he has served as consultant for Allos, Astellas, Lilly, and Millennium and has received research support from Allos, Astellas, Lilly, Merck, Millennimum, and Spectrum.

Julie M. Vose, MD, has disclosed that she has received research funding from Allos Therapeutics, AstraZeneca, Bristol-Myers Squibb, Celgene, Exelixis, Genentech, Genzyme, GlaxoSmithKline, Novartis, Pharmacyclics, and US Biotest.


Mantle Cell Lymphoma

Median age: 58 yrs

M:F ratio: 3:1

Typically advanced stage

B symptoms: < 50% cases

90% extranodal involvement: BM, blood, liver, GI

Generalized adenopathy: 70% to 90%

CNS involvement at relapse: 4% to 22% (↑ with blastoid)

Fisher RI. Ann Oncol. 1996;7(suppl 6):S35-S39. Armitage JO. Oncology (Williston Park). 1998;12(10 suppl 8):48-55. Romaguera JE, et al. Cancer. 2003;97:586-591. Gill S, et al. Leuk Lymphoma. 2008;49:2237-2239.

Frontline MCL Therapy


R-CHOP vs CHOP in Untreated MCL

64 patients randomized in each arm

No differences observed in PFS or OS between treatment arms

Lenz G, et al. J Clin Oncol. 2005;23:1984-1992.

Response, % R-CHOP CHOP P Value

RR 94 75 .005

CR 34 7 .0002


STiL: Frontline B-R vs R-CHOP

Primary endpoint: PFS (noninferiority B-R < 10% at 3 yrs)

Secondary endpoints: ORR, CR, toxicity, stem cell mobilization

Bendamustine-Rituximab (n = 260)B 90 mg/m2 on Days 1, 2 +

R 375 mg/m2 on Day 1Max 6 cycles q4w

R-CHOP (n = 253)Max 6 cycles q3w

CD20+ FL, SLL, MZL, MCL, LPL,

stage III-IV,untreated, 18 yrs

of age or older

(N = 549)

Rummel MJ, et al. ASH 2009. Abstract 405.


STiL: BR vs R-CHOP, All Disease Types

513 evaluable patients > 1/2 FL/18% MCL

No difference in ORR between treatment arms

CR

– B-R: 40%

– R-CHOP: 31%

– P = .03

BR toxicity profile: alopecia, neutropenia, thrombocytopenia, infections

Rummel MJ, et al. ASH 2009. Abstract 405.

PFS

– B-R: 55 mos

– R-CHOP: 35 mos

– P < .05

Dose-Intensive Approaches


MCL: High-Dose Therapy/ASCT—CHOP Backbone

Tripled CR rate after DHAP (12% vs 61%)[2]

Median EFS: 84 mos vs 51 mos prior to rituximab[1]

Response, Yrs IFN Arm ASCT arm P Value

Median DOR 1.6 3.7 .0004

Median TTF (ITT) 1.4 2.6 .0001

OS 5.4 7.5 .075

1. Lefrere F, et al. Leukemia. 2002;16:587-593. 2. Delarue R, et al. ASH 2008. Abstract 581. 3. Dreyling M, et al. ASH 2008. Abstract 769. Dreyling M, et al. Blood. 2005;105:2677-2684.

1.0

0.8

0.6

0.4

0.2

0

Su

rviv

al P

rob

abil

ity

Yrs After End of Induction Therapy0 1 2 3 4 5 6

ASCTIFNP = .0108

Pts at Risk, nASCTIFN

62 38 31 17 10 360 33 19 9 6 2

1.0

0.8

0.6

0.4

0.2

0

P (

EP

S)

Mos0 10 20 30 40 50 60


0

20

40

60

80

100

MCL: High-Dose Therapy/ASCT—More Intensive Induction

Small series

Long follow-up

Bias? (toxic regimen)

EFS, PFS, OS, and mol CR/previous CHOP—ASCT

Preemptive rituximab maintenance based on QPCR

MCL3/similar + ibritumomab tiuxetan prior ASCT[3]

Magni M, et al. Bone Marrow Transplant. 2009;43:509-511. 2. Geisler et al. Blood. 2008;112:269-293. 3. Kolstadt, et al. ASH 2009. Abstract 932.

EFS EFSABR-HDS low riskR-HDS int-high risk MCL2 (n = 160)

MCL1 (n = 41)

Per

cen

t S

urv

iva

l

Per

cen

t S

urv

iva

l

Mos Yrs0 2 4 6 8 10

P < .0001

0 24 48 960

20

40

60

80

100

P < .0001

1201088472603612


EU Trial: MCL Younger Protocol Design

Primary endpoint: time to treatment failure

Secondary endpoints: response rates, OS, toxicity

Hermine O, et al. ASH 2010. Abstract 110.

(2 + 1) x R-CHOP/DHAP

alternating(stem cell mobilization

after course 6)

TBI 10 GyAra-C 4 x 1.5 g/m2 +

Melphalan 140 mg/m2 +PBSCT

Patients younger than 65 yrs of age with MCL, ECOG PS < 2,

Ann Arbor stage II-IV,

eligible for high-dose therapy

4 x R-CHOP2 x R-CHOP

DexaBEAM (stem cell mobilization)

Cyclo 120 mg/kg + TBI 12 Gy

PBSCT


1.0

0.8

0.6

0.4

0.2

0

1.0

0.8

0.6

0.4

0.2

0

EU Trial: Results


Time to Treatment Failure PP MCL Younger: Remission Duration After ASCT

Pro

bab

ilit

y

0 12 24 36 48 60 72Mos Since Randomization

Pts at Risk, n208 147 99 67 29 11 0212 134 95 66 36 11 0

R-DHAPR-CHOP

HR: 0.68

P = .0382 (1-sided sequential test)

Median follow-up: 32 mosR-DHAP, median not reachedR-CHOP, median: 49 mos

Pro

bab

ilit

y

0 12 24 36 48 60 72Mos Since Retransfusion

Pts at Risk, n133 99 69 45 19 0133 92 66 43 15 1 0

R-DHAPR-CHOP

P = .0059

Median follow-up: 30 mosR-DHAP, median not reachedR-CHOP, median: 48 mos


High-Dose Therapy/ASCT: Summary

No difference in ORR (97%) or CR/CRu (79/82%) post- ASCT


Measure, n (%) R-CHOP R-CHOP/R-DHAP

P Value

CR 54 (26) 72 (36) .032

CR or CRu 83 (40) 111 (55) .0028

CR or CRu or PR 186 (90) 188 (94) .14

Relapse after CR/CRu/PR 49 (23) 22 (10) --


Comparison of Dose-Intensive/High-Dose Therapy in MCL Ara-C–containing induction regimens for MCL

Study Therapy N Age Limit, Yrs

5-Yr EFS, %

5-Yr OS, %

Follow-up, Mos

Nordic[1] MCL-2 (R + Maxi-CHOP +

HD Ara-C + Maint R)

160 < 66 63 74 40

GITIL[2] (R) HDS-ASCT* 77 < 61 61 74 50

MDACC[3,4] R-HyperCVAD 97 Up to 80 (1/3 > 65)

48 (FFS) 65 50

≤ 65 60 (FFS) 76 50

CALGB R-Maxi-CHOP-MTX/VP16-Ara-C/CBV

78 18-69 56 (PFS 64 50

EU younger patients

R-CHP/DHAP-TAM → ASCT

208 < 65 65 (TTF) 78 32

1. Geisler CH, et al. ASH 2007. Abstract LBA1. 2. Cortelazzo S, et al. ASH 2007. Abstract 1282. 3. Romaguera JE, et al. J Clin Oncol. 2005;23:7013-7023. 4. Fayad L, et al. Clin Lymphoma Myeloma. 2007;8(suppl 2):S57-S62.

*4 MDS and 3 solid tumors. Compare to R-CHOP PFS 25% at 52 yrs


SWOG 0213: R-HyperCVAD in MCL

Measure Outcome

Median age, yrs 57

Mantle zone variant, %

57

Grade 3/4 infection, %

34

Discontinued Rx/toxicity, %*

42

Efficacy, n (%)

ORR 35 (88)

CR/CRu 23 (58)

PR 12 (30)

Survival, % 1 Yr 2 Yrs

PFS 89 64

OS 91 76

Epner EM, et al. ASH 2007. Abstract 387.

*No details on dose reductions

Yrs From Registration

0

20

40

60

80

100

0 1 3 52 4

OS

PFS

Pat

ien

ts (

%)

6


Kahl BS, et al. Ann Oncol. 2006;17:1418-1423.

CR,CRu,PR

ASSESS

Rituximab 375 mg/m2 on Day 1 +Cyclophosphamide 300 mg/m2 q12 hrs on Days 1-3 +

Doxorubicin 50 mg/m2 48-hr CI on Days 1-2 +Vincristine 2 mg IV on Day 3 +

Dexamethasone 40 mg PO on Day 1-4

Rituximab375 mg/m2

once wkly × 4q6m × 4

22 untreated MCL

Toxicity mainly hematologic

Clinical Response, % Patients

ORR (n = 22) 77

CR/CRu 64

PR 14Median PFS: 37 mos

PFS

Median OS: not reached

0 10 20 30 40 50 600

20

40

60

80

100

OS

Mos

Pat

ien

ts A

live

(%)

Median follow-up: 37 mos

No vincristine or steroids on Day 11/no methotrexate, no Ara-C/monthly cycles x 6

Modified R-HyperCVAD: Design


NCCN Study in MCL: PFS

LaCasce A, et al. ASH 2009. Abstract 403.

PFS K-M 2-Group Log Rank P Value

R-hyperCVAD vs R-CHOP < .001

R-CHOP+HDT/ASCR vs R-CHOP < .001

R-hyperCVAD vs R-CHOP + HDT/ASCR .58


OS K-M 2-Group Log Rank P Value

R-hyperCVAD vs R-CHOP .02

R-CHOP+HDT/ASCR vs R-CHOP .20

R-hyperCVAD vs R-CHOP + HDT/ASCR .64

NCCN Study in MCL: OS

LaCasce A, et al. ASH 2009. Abstract 403.


Forstpointner R, et al. Blood. 2004;104:3064-3071.

FCM vs R-FCM in Relapsed Indolent Lymphoma

4 cycles FCM vs R-FCMRelapsed indolent lymphoma

FludarabineCyclophosphamide

Mitoxantrone

FludarabineCyclophosphamide

Mitoxantrone+ Rituximab

R

128 patients evaluable with relapsed indolent NHL; 48 evaluable patients with MCL

Outcome in MCL Patients FCM(n = 24)

FCM-R (n = 24)

P Value

ORR, % 46 58 .282

CR, % 0 29 NR

Median PFS, mos 4 8 .3887

Median OS, mos 11 Not reached .0042


1. Zelenetz A, et al. ASCO 2006. Abstract 7560. 2. Smith M, et al. ASH 2007. Abstract 389.

Study Design Results/Comments

MSKCC 01-029[1]

Tositumomab CHOP x 6No rituximab

Feasible35% eval pts had mol CR post-RITNot improved post-CHOP

ECOG 1499[2] R-CHOP x 4 Ibritumomab tiuxetan

56 pts/med age: 61 yrsTripled CR rate: 45% (14% after R-CHOP)Med FFS at 27 mos(> R-CHOP alone)

Frontline Radioimmunotherapy in MCL


Radioimmunotherapy in MCL

Study Design Results/Comments

I131Tositumomab + HDT cyclophosphamide + etoposide + ASCTFHCRC[1]

34 pts heavily pretreatedMed number of previous Rx: 3 (106)50% refractory to last Rx5-yr PFS: 42%

High-dose IbritumomabTiuxetan + ASCT in DLCL and MCLCity of Hope[2]

42 pts, 1/3 MCLMed number of previous Rx: 2 (1-6)

1. Gopal AK, et al. Blood. 2002;99:3158-3162. 2. Krishnan A, et al. J Clin Oncol. 2008;26:90-95.

Relapsed/Refractory MCL


1. Inwards DJ, et al. Cancer. 2008;113:108-116. 2. Ogura M, et al. ASH 2009. Abstract 3694. 3. Rummel MJ, et al. J Clin Oncol. 2005;23:3383-3389. 4. Robinson KS, et al. J Clin Oncol. 2008;26:4473-4479.

Relapsed/Refractory MCL

Agent Regimen Outcomes

Cladribine Single agent[1]

25 pts with recurrent diseaseORR: 46%; CR: 21%Median PFS: 5.4 mos

Bendamustine

Single agent[2]

Bendamustine + rituximab[3]

16 MCL patientsORR: 75%; CR: 50%Median PFS: 18 mos

Bendamustine + rituximab[4]

12 MCL patientsORR: 92%; CR/CRu: 59%

Median DOR: 19 mos


Single-Agent Y-90 Ibritumomab Tiuxetan for Relapsed/Refractory MCL N = 34

Median age: 68 yrs; median previous regimens: 3

Dosed by platelet count

– ≥ 150,000 cells/mm3: 0.4 mCi/kg

– < 150,000 to ≥ 150,000 cells/mm3: 0.3 mCi/kg

ORR: 31%

Median EFS: 6 mos (28 mos for patients with response)

Median OS: 21 mos

Grade 3/4 thrombocytopenia: 24%; grade 3/4 neutropenia: 32%

Wang M, et al. J Clin Oncol. 2009;27:5213-5238.


1. O’Connor OA, et al. Br J Haematol. 2009;145:34-39. 2. Goy A, et al. J Clin Oncol. 2005;23:667-675. 3. Strauss SJ, et al. J Clin Oncol. 2006;13:2105-2112. 4. Belch A, et al. Ann Oncol. 2007;18:116-121. 5. Fisher RI, et al. J Clin Oncol. 2006;24:4867-4874.

Similar ORR across studies and for untreated/relapsed

1.5

mg

/m2

1.3

mg

/m2

Bortezomib: Summary of Efficacy in Mantle Cell Lymphoma

Study N CR, n (%) PR, n (%) ORR, % (n)

O’Connor[1] 40 5 (13) 14 (35) 47

Goy[2] 29 6 (21) 6 (21) 41

Strauss[3] 24 1 (4) 6 (24) 29

Belch, n[4] 13 untreated/ 15 relapsed

01

66

4647

PINNACLE[5] 141 11 (8) 36 (26) 47 (33)

Total 262 24 (9) 74 (28) 98 (37)


PINNACLE Trial Update

Response/Subsets Analysis

*Refractory subgroup: no response or response with TTP < 6 mos to last previous line of therapy.†High-intensity subgroup: ASCT or therapies containing high-dose cytarabine or ifosfamide/carboplatin etoposide.

Goy A, et al. Ann Oncol. 2009;20:520-525.

Parameter Response: Evaluable(n = 141)

Refractory MCL*(n = 51)

Previous High-Intensity Therapy†

(n = 52)

ORR, % 32 29 25

CR/CRu, % 8 6 10

Median DOR, mos 9.2 5.9 Not reached

Among patients who achieved CR/CRu: median DOR not reached at 26.4 mos


Early Data of Combination BortezomibWith Common MCL RegimensCombination Design Results Comment

R-CHOP GELA[1]

2 arms Wkly vs biwklyDose escalation in each armMCL, FL, MZL, DLCL IPI 0

48 pts 4 MCLORR 100% biwklyNeed longer follow-up

Grade 3 neurotoxicity > 20% 9/10 in biwkly + highest dose

R-CHOP Cornell[2]

R-CHOP + bortz Days 1 and 4 only ++DLCL and MCL

36 MCL Well tolerated

Modified R-hyperCVAD[3]

Modified R-hyperCVAD + bortz Days 1, 4

30 ptsORR: 90%CR: 77%

Neuropathy excessive at 1.5 dose; capped VCR at 1.0 and bortz at 1.3

Modified R-hyperCVAD[4]

Modified R-hyperCVAD + bortz 1.3 mg/m2 Days 1, 4

Classic R-hyperCVAD[5]

Full R-hyperCVADBortezomib Days 1, 4 cycle A and Days 2, 5 cycle B

16 pts phase I No unexpected toxicity so farIncluding PFTs

Bendamustine + Rituximab[6]

1. Mounier N, et al. ASCO 2007. Abstract 8010. 2. Ruan J, et al. ASH 2009. Abstract 2682. 3. Kahl B, et al. ASH 2008. Abstract 265. 4. Kahl BS, et al. ASH 2009. Abstract 1661. 5. Romaguera J. ICML 2008. Abstract 444. 6. Friedberg JW, et al. ASH 2009. Abstract 924.


Lenalidomide: IMiDs

Lenalidomide mechanism of action remains poorly understood

Antiangiogenic, microenvironment, direct antiproliferative, NK, and T-regs

List AF. N Engl J Med. 2007;357:2183-2186. Copyright © 2007 Massachusetts Medical Society. All rights reserved.


Lenalidomide in MCL: Phase II NHL-003 Trial N = 203; MCL pts, n = 53 Median number of previous Rx: 3 (1-8) DOR: NR (13.7 mos in previous NHL-002 trial)

Results %

Response

ORR 4114 patients previous bortezomib 57

CR/CRu 13

PR 28

SD 26

PD 33

Toxicity (myelotoxicity)*

Dose reductions 38

Zinzani PL, et al. ASH 2008. Abstract 262. Reeder CB, et al. ASH 2008. Abstract 1560. Czuczman MS, et al. ASH 2008. Abstract 268. Habermann TM, et al. Br J Haematol. 2009;145:344-349.


CALGB 50501: Bortezomib + Lenalidomide in Rel/Ref MCL—Planned Interim Analysis Eligibility

– Histologically documented MCL (CD5+, CD23-, cyclin D1+)

– Measurable disease

– PD 0-2

– Previous treatment with ≥ 1 regimen (including autologous SCT)

– No previous radioimmunotherapy

– No ≥ 3 grade 3 PN

Morrison VA, et al. ASCO 2010. Abstract 8106.


CALGB 50501: Bortezomib + Lenalidomide in Rel/Ref MCL—Planned Interim Analysis Induction therapy given every 21 days for 8 cycles

– Lenalidomide 20 mg PO QD on Days 1-14

– Bortezomib 1.3 mg/m2 on Days 1, 4, 8, 11

Responding patients at 6 mos continued to maintenance therapy

Primary endpoint: ORR

Secondary endpoints: TTP, DFS/OS, correlating changes in activate NK/T cells and plasma cytokines with response



CALGB 50501: Bortezomib + Lenalidomide in Rel/Ref MCL—Planned Interim Analysis Target accrual: 54 patients

Planned interim analysis performed at 19 patients

Grade 3/4 toxicity data for 31 patients

– Anemia: 3/0

– Leukopenia: 3/0

– Thrombocytopenia: 19/13

– Fatigue/asthenia: 19/0

– Dyspnea: 16/0


– Infection: 6/0

– Motor neuropathy: 13/0

– Sensory neuropathy: 3/0

– Hypotension: 13/0


Targeting the PI3K/mTOR Pathway

Key pathway for multiple receptor tyrosine kinases/cell proliferation and protein translation

Activated Ras

PI3K

PIP2 PIP3

PTENILK PDK1

Akt pAkt ppAkt

pTSC2+

TSCI

TSC1-TSC2

Rheb.GTP Rheb.GTPRapamycin

+FKBP12

p70S6keIF4E.4EBP-1 complex

Cyclin D1 mRNA Cyclin D1 protein

p70S6k

S6P

PP 4E-BP1+

eIF4E

Rapamycin + FKBP12

Protein S6


Hess G, et al. J Clin Oncol. 2009;27:3822-3829.

Temsirolimus 175 mg QW x 3then 25 mg QW

Relapsed/refractory MCL

Requiredrituximab

anthracyclinealkylating agent

(N = 162) Investigators’ choice single agent

Temsirolimus 175 mg QW x 3then 75 mg QW

Multicenter, open-label, phase III trial

Temsirolimus (CCI-779) in MCL


Temsirolimus (CCI-779) in MCL

Response Temsirolimus 175/75(n = 54)

Temsirolimus 175/25(n = 54)

Investigators’ Choice(n = 54)

ORR, % 22* 6 2

Median DOR, mos 7.1 3.6 NA

Median PFS, mos 4.8† 3.4 1.9

Median OS, mos 11.1 8.8 9.5

*P vs investigator choice = .0019; †P vs investigators’ choice = .0009

Hess G, et al. J Clin Oncol. 2009;27:3822-3829.


Kouroukis CT, et al. J Clin Oncol. 2003;21:1740-1745. Lin TS, et al. Leuk Lymphoma. 2002;43:793-797. Byrd JC, et al. Blood. 2007;109:399-404.

Targeting Cyclin/CDK complexes

Flavopiridol

Semisynthetic flavone analogue of rohitukine (Indian tree) that blocks several CDKs, including complex CDK4-cyclin D1

Initial schedules: ORR 11% (only PR)/strong binding to human proteins

– LC50 required 5 x higher with human serum

Pharmacologically modified schedules very promising

– 30-min bolus followed by 4-hr infusion

CLL

– ORR 45%, med DOR > 12 mos, even in p53-deleted pts

– 55% grade 3/4 lysis syndromes +++, thrombocytopenia

Other CDK inhibitors coming: PD0332991 ++


Gemcitabine in MCL

Single-agent gemcitabine (N = 18; 9 newly diagnosed, 9 relapsed)[1]

– Response rate: 5/18 (28%)

– CR: n = 1; PR: n = 4

– Median treatment response duration: 10.6 mos

Gemcitabine/mitoxantrone/rituximab for relapsed/refractory (N = 16)[2]

– Best responses

– CR: 20%; PR: 27%

– Grade 3/4 toxicities: neutropenia (100%), thrombocytopenia (67%), leukopenia (53%), anemia (33%)

– Median PFS and OS not reached at 10.7 mos

1. Hitz F, et al. Hematol Oncol. 2009;27:154-159. 2. Garbo LE, et al. Invest New Drugs. 2009;27:476-481.


MIPI and Survival in Patients Receiving RHCVAD and R-MTX-Ara-C Single-agent, retrospective cohort study

Study designed to identify predictors of survival on patients on first-line RHCVAD therapy

Primary endpoints: OS and PFS assessed by chart review

Analysis included 53 patients with advanced MCL receiving RHCVAD alternating with R-MTX-Ara-C every 21 days (median: 6 cycles)

Mato AR, et al. ASCO 2010. Abstract 8092.


MIPI and Survival in Patients Receiving RHCVAD and R-MTX-AraC: Results Median OS and PFS not yet reached (median follow-up:

18 mos [range: 35-74])

MIPI classified 47%, 29%, and 24% of patients as low, intermediate, and high risk

– MIPI did not identify 3 distinct categories by K-M analysis for OS or PFS

Univariate analysis showed blastoid variant only significant predictor for OS (HR: 9.4; 95% CI: 1.2-53.1)

Age, ECOG PS, WBC, LDH, β2-microglobulin not predictive of OS

Blastoid variant (HR: 8.8; P .05) and β2-microglobulin (HR: 1.9; P .01) were independent predictors for PFS

Mato AR, et al. ASCO 2010. Abstract 8092.


Tam CS, et al. Blood. 2009;113:4144-4152.

Risk-Adapted Transplantation in MCL

Retrospective study of mature results of 17 yrs of transplantation experience in 121 MCL patients at M. D. Anderson Cancer Center

– AUTO1 (n = 50): patients who received autologous SCT during first CR or PR

– AUTO2 (n = 36): patients who received autologous SCT for relapsed/refractory disease

– NST (n = 35): patients who received nonmyeloablative SCT for relapsed/refractory disease


Tam CS, et al. Blood. 2009;113:4144-4152. This research was originally published in Blood. © American Society of Hematology.

MCL: ASCT/Allogeneic Transplantation

Single institution/not very large numbers ASCT in first CR > ASCT in relapse (but no plateau either way)

Mini-allo ~ 50% at 5 yrs: prediction is PBSCT and chimerism ≥ 95%

PFS (Mos)

Pro

po

rtio

n A

live

Wit

ho

ut

Pro

gre

ssio

n

0

0.2

0.4

0.8

1.0

0 144

AUTO1 (n = 50)AUTO2 (n = 36)

0.6

12 24 36 48 60 72 84 96 108120 132

NST (n = 35)

P = .01P = .01

OS (Mos)P

rop

ort

ion

Ali

ve

0

0.2

0.4

0.8

1.0

0 144

AUTO1 (n = 50)AUTO2 (n = 36)

0.6

12 24 36 48 60 72 84 96 108120 132

NST (n = 35)

P = .02P = .10*

*P = .006 at 4 yrs landmark


Drug Mechanisms/Study

Other antiangiogenesis agents Thalidomide/rituximab/bevacizumab/VEGF Trap

Anti-TRAIL antibodies (TRM-1)

Fully human Mab agonistic to the TRAIL receptor 1Induction apoptosis/extrinsic pathway

HSP inhibitors17AAG (geldamycin)

Rationale to overcome bortezomib resistance

IKK inhibitors Stabilization of NF-κB

Inhibitors of Raf/MEK signaling pathway

Sorafenib, orally administered Small-molecule signal transduction inhibitor

HDAC inhibitors (SAHA, depsipeptide)

SAHA showed activity in MCL in preclinical models

Farnesyl transferase inhibitors Tipifarnib/ongoing

BL22 immunotoxin Calicheamicin/CD22 (CMC-544)

Others Bcl-2 inhibitors

Other Novel Agents in MCL

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Case-Based Workshop With the Experts: Evolving Management Strategies in Non-Hodgkin’s Lymphoma This program is supported by educational grants from