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LATEST CONCEPTS IN LARGE CELL AND HODGKIN LYMPHOMAS. Morton Coleman, M.D. Director, Center for Lymphoma and Myeloma New York-Presbyterian Hospital Weill Cornell Medical Center Clinical Professor of Medicine Weill Cornell Medical College Chairman, Medical Affiliates Board

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Latest concepts in large cell and hodgkin lymphomas

LATEST CONCEPTS IN LARGE CELL AND HODGKIN LYMPHOMAS

Morton Coleman, M.D.

Director, Center for Lymphoma and Myeloma

New York-Presbyterian Hospital Weill Cornell Medical Center

Clinical Professor of Medicine

Weill Cornell Medical College

Chairman, Medical Affiliates Board

Lymphoma Research Foundation


Disclosures for Morton Coleman, MD

In compliance with ACCME policy, ASH requires the following disclosures to the session audience:

2012 Clinical Research Training Institute Summer Workshop, La Jolla, CA


Disclosures for Morton Coleman, MD, con’t

In compliance with ACCME policy, ASH requires the following disclosures to the session audience:

2012 Clinical Research Training Institute Summer Workshop, La Jolla, CA


The thrust of current developments
THE THRUST OF CURRENT DEVELOPMENTS

  • Identify subsets of patients with diffuse large B cell or Hodgkin lymphoma who are either destined to do well or fare poorly using techniques beyond the known clinical predictive factors, particuarly those techniques using molecular changes and/or PET scans.

  • By applying our better understanding of the (molecular) biology of these diseases, can we not only identify these subsets, but also develop and individualize treatments using less therapy for those with a good prognosis and using novel therapies for those destined to do poorly.


R chop 21 14 cures about 2 3 of all comers failure free survival
R-CHOP-21/14 cures about 2/3 of“all comers”: Failure-free survival

1.0

0.9

0.8

0.7

0.6

Probability

R-CHOP21

R-CHOP14

0.5

Events, n (%)

155 (29)

153 (28)

0.4

2-yr FFS

75%

75%

0.3

Log-rank test

p=0.94

0.2

HR (95% CI)

0.99 (0.79–1.24)

R-CHOP14

0.1

R-CHOP21

0.0

0

1

2

3

4

5

6

Years from randomisation

Patients at Risk

R-CHOP21

534

429

358

216

116

25

1

25

102

1

R-CHOP14

533

355

438

224

Cunningham et al, ASCO 2011


DLBCL patients who recur post R-CHOP-21

do not do well

N=228

31%

Gisselbrecht C, et al. J Clin Oncol 2009; 27(15s): Abstract 8509.


Overall survival of patients with dlbcl refractory to second line therapy is very poor
Overall survival of patients with DLBCL refractory to second line therapy is very poor

0.00 0.25 0.50 0.75 1.00

Proportion of Patients

0 5 10 15 20 25

Time (months)

Elstrom et al , Clin Lymph Myel Leuk, 2010


Germinal center vs activated B cell DLBCL line therapy is very poor

Rosenwald A et al. N Engl J Med. 2002;346:1937-1947


Outcome by GCB vs non-GCB gene signatures in DLBCL line therapy is very poor

N=233 patients treated with R-CHOP

OS

PFS

Lenz G, et al, NEJM November 27, 2008


GCB line therapy is very poor

+

CD10

-

?

HGAL

BCL6

BCL2

-

+

?

non-GCB

MUM1

-

+

FOXP1


Non gcb dlbcl is associated with high expression of target genes of nf kb transcription factors
Non-GCB DLBCL is associated with high expression of target genes of NF-kB transcription factors

Davis, et al, J Exp Med 2001


CHOP-R + bortezomib DLBCL PFS and OS by subtype (n = 40) genes of NF-kB transcription factors

Ruan et al, JCO 2010


Pyramid study design
PYRAMID study design genes of NF-kB transcription factors

DLBCL diagnosis & subtyping

Hans method

Non-GCB

GCB

Not enrolled

R

Vc-R-CHOP

Bortezomib 1.3 mg/m2, d 1, 4

Rituximab 375 mg/m2, d 1

Cyclophosphamide 750 mg/m2, d 1

Doxorubicin 50 mg/m2, d 1

Vincristine 1.4 mg/m2, d 1

Prednisone 100 mg/d, d 1–5

Six treatment cycles q21 days

R-CHOP

Rituximab 375 mg/m2, d 1

Cyclophosphamide 750 mg/m2, d 1

Doxorubicin 50 mg/m2, d 1

Vincristine 1.4 mg/m2, d 1

Prednisone 100 mg/d, d 1–5

Six treatment cycles q21 days

Follow up every 3 months for 2 yrs


What is a double hit lymphoma
What is a “double hit” lymphoma? genes of NF-kB transcription factors

  • Recurrent breakpoints activating multiple oncogenes, one being MYC

  • BCL2+/MYC+ most common

  • BCL6, CCND1 and BCL3 may also occur

  • Can also have “triple hit”


Immunophenotype of double hit lymphoma
Immunophenotype of “double hit” lymphoma genes of NF-kB transcription factors

  • CD10+, GCB phenotype

  • Lack MUM1, ABC phenotype

  • BCL2 + also present (with Myc) in a majority of cases

  • High proliferative index

    • median 90% Ki67+

Aukema et al, Blood 2011


Clinical features of double hit lymphoma
Clinical features of “double hit” lymphoma genes of NF-kB transcription factors

Aukema et al, Blood 2011


R chop and myc rearranged dlbcl
R-CHOP and MYC rearranged DLBCL genes of NF-kB transcription factors

35 (14%) with MYC

rearrangements

19 also had t(14;18)

3 also had BCL6

7 “triple hit”

Therefore most

“MYC+” are “double”

or “triple” hit

EFS

OS

Barrans et al, JCO 2010


Da r epoch and myc dlbcl
DA-R-EPOCH and MYC+ DLBCL genes of NF-kB transcription factors

9 MYC+ DLBCL

99 MYC- DLBCL

Similar

risk by IPI

High RR/PFS in

BL

EFS

OS

Dunleavy et al, Lugano 2011


Impact of Induction Regimen and Consolidative Stem Cell Transplantation in Patients with Double Hit Lymphoma (DHL): A Large Multicenter Retrospective Analysis

Mitul Gandhi, Adam M. Petrich, Ryan Cassaday, Oliver Press, Khushboo A. Shah, Jeremy D. Whyman, Frederick Lansigan, Andrew Zelenetz, Namrata Shah, Timothy Fenske, Francisco J. Hernandez-Ilizaliturri, Lisa X. Lee, Stefan K. Barta, Shruthi Melinamani, Reem Karmali, Camille Adeimy, Scott Smith, Julie Vose, Neil Dalal, Chadi Nabhan, David Peace, Borko Jovanvoic, Aliyah Sohani, Andrew Evens, Jorge Castillo, Jeremy S. Abramson

ASH 2013, Abstract 40


Dhl impact of r epoch
DHL: Impact of R-EPOCH Transplantation in Patients with Double Hit Lymphoma (DHL): A Large Multicenter Retrospective Analysis

  • Results of chi-square analysis

    • Improved CR compared to R-CHOP (p = .005)

    • Trend towards improvement w/ other regimens (p = .07)

    • Decreased PD compared to R-CHOP (p = .005)

    • Decreased PD w/ other intensive regimens (p = .003)


Dhl conclusions
DHL: Conclusions Transplantation in Patients with Double Hit Lymphoma (DHL): A Large Multicenter Retrospective Analysis

DHL has a poor prognosis, although a subset exists which can achieve durable CR

R-EPOCH is associated with improved rates of CR and decreased rates of PD

SCT does not clearly improve OS compared to observation alone in those achieving CR

Novel approaches and agents are necessary to overcome unfavorable biology


ASH 2013, Transplantation in Patients with Double Hit Lymphoma (DHL): A Large Multicenter Retrospective AnalysisAbstract 371

A Phase III Study of Enzastaurin in Patients with High-risk Diffuse Large B Cell Lymphoma Following Response to Primary Treatment:

The PRELUDE Trial

Michael Crump; Sirpa Leppä; Luis Fayad; Je Jung Lee; Alice Di Rocco; Michinori Ogura; Hans Hagberg; Frederick Schnell; Robert Rifkin; Andreas Mackensen; Fritz Offner; Lauren Pinter-Brown; Sonali Smith; Kensei Tobinai; Su-Peng Yeh; Jun Zhu; Eric D. Hsi; Marjo Hahka-Kemppinen; Scott P. Myrand; Donald Thornton; Peipei Shi; Tuan Nguyen; Boris Lin; Brad Kahl; Norbert Schmitz; Kerry J. Savage; Thomas Habermannfor PRELUDE Trial Investigators


Background
Background Transplantation in Patients with Double Hit Lymphoma (DHL): A Large Multicenter Retrospective Analysis

  • Patients with DLBCL and an IPI score of 3-5 at diagnosis who relapse after R-CHOP can have a poor prognosis.

  • Enzastaurin is a potent and selective competitive inhibitor of PKCβ.1,2

  • Enzastaurin was associated with freedom from progression in a phase II trial in a small subgroup of patients with relapsed or refractory DLBCL, thereby providing the rationale for this study.3

R-CHOP = rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone.

The PRELUDE Trial

1Morgillo F, et al. Mol Cancer Ther 2008;7:1698-707; 2Dumstorf CA, et al. Mol Cancer Ther 2010;9:3158-63; 3Robertson MJ, et al. J Clin Oncol 2007;25:1741-6.


Background1
Background Transplantation in Patients with Double Hit Lymphoma (DHL): A Large Multicenter Retrospective Analysis

PKCβ is the major isoform expressed in normal and malignant B cells.1,2

BTK

SYK

  • PKCβ is required for B cell receptor signaling, activation of NFκB, and VEGF-mediated angiogenesis.3

P

P

PI 3K

AKT

  • Over-expression of PKCβ mRNA and protein is associated with a poor outcome in patients with DLBCL.1

mTOR

IKK

PLC2

NFKB

PKCβ

DLBCL = diffuse large B cell lymphoma.

The PRELUDE Trial

1Shipp MA, et al. Nat Med 2002;8:68-74; 2Graff JR, et al. Cancer Res 2005;65:7462-9; 3Robertson MJ, et al. J Clin Oncol2007;25:1741-6.


Disease free survival by treatment arm for itt population
Disease Free Survival by Treatment Arm for ITT Population Transplantation in Patients with Double Hit Lymphoma (DHL): A Large Multicenter Retrospective Analysis

100

80

60

40

20

0

Survival Probability

Enzastaurin

Placebo

HR (95% Cl): 0.92 (0.689, 1.216)

P = 0.541

p=0.541

0 6 12 18 24 30 36 42 48 54 60 66 72 78

Disease-Free Survival Time (months)

Patients at risk, n:

Patients at Risk, (n):

Disease-free Survival Time (months)

Enza:

Placebo:

504 383 348 259 157 45

254 197 165 138 74 18

The PRELUDE Trial


Disease free survival gcb vs non gcb by hans algorithm
Disease-free Survival – GCB vs. Non-GCB by Hans’ Algorithm

GCB vs. non-GCB in the Combined Arm

GCB (N=109)

GCB, Enzastaurin (N=79)

GCB, Placebo (N=30)

Survival Distribution Function

Non-GCB (N=106)

Non-GCB, Enzastaurin (N=66)

Non-GCB, Placebo (N=40)

1.0

0.9

0.8

1.0

0.9

0.8

1.0

0.9

0.8

Time (Months)

0.7

0.6

0.5

0.7

0.6

0.5

0.7

0.6

0.5

HR (95% Cl): 0.92 (0.56, 1.52)

P=0.74

Survival Distribution Function

Survival Distribution Function

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

GCB vs. non-GCB in the Placebo Arm

GCB vs. non-GCB in the Enzastaurin Arm

GCB, Placebo (N=30)

GCB, Enzastaurin (N=79)

Non-GCB, Placebo (N=40)

Non-GCB, Enzastaurin (N=66)

Time (Months)

Time (Months)

HR (95% Cl): 1.31 (0.56, 3.08)

P=0.54

HR (95% Cl): 0.77 (0.42, 1.42)

P=0.40

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

Cox regression determined associations between DFS and GCB/non-GCB status, adjusted for IPI score (3 vs. >3), age (≤60 vs. >60), and prior radiation (yes vs. no).

The PRELUDE Trial


Discussion and conclusions
Discussion and Conclusions Algorithm

The PRELUDE Trial

Enzastaurin did not improve DFS, EFS, or OS vs. placebo in patients with CR after initial treatment for DLBCL and an IPI score of ≥3

Safety results of PRELUDE were consistent with the established safety profile of enzastaurin when used as a single-agent therapy in lymphoma and other cancers

Cell-of-origin (GCB vs. non-GCB) was not prognostic for DFS in patients with CR


Bendamustine with rituximab vitamin r
BENDAMUSTINE Algorithm(with rituximab, vitamin R)

Three studies reported: Japan, NSH, Germany

Doses of B were 120mgm/m2 days 1,2 + R 375 mgm/m2 every three weeks.

German study was with unrx’ed elderly (E)

Responses ranged from 58% to 69% (E)

CR’s ranged from 19% to 54% (E)

PFS/OS ranged from 6 to 7.7(E) months

Significant toxicity


Approach to variant dlbcls
Approach to “variant” DLBCLs Algorithm

  • GCB vs non-GCB

    • R-CHOP is standard

    • Various randomized trials underway

  • MYC+, DH, TH

    • Consider FISH/IHC for MYC, BCL2, BCL6

    • Less favorable with R-CHOP

    • Unclear if other approaches better

    • Prospective studies underway, including R-EPOCH

  • Intensive BL type regimens

  • R-EPOCH

  • Less favorable outcome than other DLBCL with R-CHOP

    • Risk seems to be beyond age, IPI

  • Less favorable at progression

  • Rearrangements noted

    • BCL2 31%

    • BCL6 18%

    • C-MYC 13%

  • C-MYC worse PFS and OS


In hodgkin lymphoma what role do pet scans play in lessening toxicity therapy and enhancing cure

In Hodgkin lymphoma, what role do PET Scans play in lessening (toxicity) therapy and enhancing cure?

May interim PET/CAT scans be of value or should scans be used only at the end of treatment?


Fdg pet after one two treatments versus two cycles four treatments of therapy

FDG-PET: After one (two treatments) versus two cycles (four treatments) of therapy

Early determination of treatment sensitivity in Hodgkin lymphoma: FDG-PET/CT after one cycle of therapy has a higher negative predictive value than after two cycles of therapy

Hutchings, M., Kostakoglu,L., Coleman, M., et al. Submitted for publication


Participating nations
Participating Nations treatments) of therapy

Denmark

United States

Italy

Poland


Patient population 126 pts
Patient Population:126 Pts. treatments) of therapy

  • Stage I 8%

  • Stage 2 46%

  • Stage 3 19%

  • Stage4 27%

  • B Sxs 56%

  • Bulky 37%


Comparison of the prognostic value of PET 1 and PET 2: Progression Free Survival at 2 Years PET 1 PET2

Negative predictive value 98% 91%

Positive predictive value 63% 85%

Sensitivity 95% 61%

Specificity 86% 97%

Concordance >90%


The RAPID Trial in Patients With Clinical Stages IA/IIA Hodgkin Lymphoma and a “Negative” PET Scan After 3 Cycles ABVD

Radford J, Barrington S, Counsell N, Pettengell R,

Johnson P, Wimperis J, Coltart S, Culligan D, Lister A, Bessell E,

Kruger A, Popova B, Hancock B, Hoskin P, Illidge T, O’Doherty M


RAPID Trial Design Hodgkin Lymphoma and a “Negative” PET Scan After 3 Cycles ABVD

Initial treatment: ABVD x 3

Reassessment: if NR/PD, patient goes off study

if CR/PR, FDG-PET scan performed

PET-positive

PET-negative

4th cycle ABVD then IFRT

Randomization

IFRT

No further treatment

Radford J, et al. Blood. 2012;120: Abstract 547.


Outcomes After Median Follow-Up of 45.7 Months Hodgkin Lymphoma and a “Negative” PET Scan After 3 Cycles ABVD

Radford J, et al. Blood. 2012;120: Abstract 547.


Summary
Summary Hodgkin Lymphoma and a “Negative” PET Scan After 3 Cycles ABVD

602 pts registered between 2003 and 2010

75% PET-negative at central review after ABVD x 3

In the randomized PET-negative population, 3 yr PFS is 93.8% IFRT and 90.7% NFT

Risk difference -3% is within the maximum allowable difference of -7%

Radford J, et al. Blood. 2012;120: Abstract 547.


Conclusion
Conclusion Hodgkin Lymphoma and a “Negative” PET Scan After 3 Cycles ABVD

Patients with a negative PET scan after 3 cycles ABVD have an excellent prognosis without further treatment, and for these patients RT can be avoided

Radford J, et al. Blood. 2012;120: Abstract 547.


Commentary
Commentary Hodgkin Lymphoma and a “Negative” PET Scan After 3 Cycles ABVD

These data are similar to those reported from Argentina several years ago.

Would the slightly higher rate of false negative PET scans at cycle 3 seen in those patients not receiving adjuvant radiotherapy been avoided had the PET been performed at cycle 2, or better yet, cycle 1

Response-adapted therapy based on quality- controlled/assured PET imaging may become the future standard of care in early-stage HL

Radford J, et al. Blood. 2012;120: Abstract 547.


An Individual Patient-Data Comparison of German Hodgkin Study Group HD10 and HD11 Combined Modality Therapy and NCIC Clinical Trials Group HD.6 ABVD Alone

Hay AE, Klimm B, Chen BE, Goergen H, Shepherd LE, Fuchs M, Gospodarowicz M, Borchmann P, Connors JM, Markova J, Crump M, Lohri A, Winter JN, Dorken B, Pearcey RG, Volker D, Horning SJ, Eich HT, Engert A, Meyer RM


Comparison of ncic ctg hd 6 and ghsg hd10 and hd11 staging eligibility and preferred arms
Comparison of NCIC CTG HD.6 and GHSG HD10 and HD11 Staging, Eligibility and Preferred Arms

2 ABVD + 20 Gy IFRT

4 ABVD + 30 Gy IFRT

Early, favorable

HD10

Early, unfavorable

HD11

Advanced

GHSG

4 – 6 ABVD alone

NCIC CTG

HD.6

Favorable

Unfavorable

Advanced

Not necessarily to scale

Hay AE, et al. Blood. 2012;120: Abstract 549.


Comparison of NCIC CTG HD.6 and GHSG HD10 and HD11 Staging, Eligibility and Preferred Arms

Very good prognosis

B or Bulk

Early, favorable

HD10

Early, unfavorable

HD11

Advanced

GHSG

NCIC CTG

HD.6

Favorable

Unfavorable

Advanced

Not necessarily to scale

Hay AE, et al. Blood. 2012;120: Abstract 549.


Outcomes all patients
Outcomes: All Patients Eligibility and Preferred Arms

Hay AE, et al. Blood. 2012;120: Abstract 549.


Overall summary
Overall Summary Eligibility and Preferred Arms

Combined modality therapy (CMT) improves disease control by 4%-7%

Superior long-term overall survival with CMT is highly unlikely

The relatively long term outcomes associated with IFRT remain to be clarified

Hay AE, et al. Blood. 2012;120: Abstract 549.


What s new for refractory relalpsing disease

What’s new for refractory/relalpsing disease? Eligibility and Preferred Arms

Evolving Data on Brentuximab Vedotin


Brentuximab vedotin mechanism of action
Brentuximab Vedotin Mechanism of Action Eligibility and Preferred Arms

Brentuximab vedotin (SGN-35) ADC

monomethyl auristatin E (MMAE), potent antitubulin agent

protease-cleavable linker

anti-CD30 monoclonal antibody

ADC binds to CD30

ADC-CD30 complex traffics to lysosome

MMAE is released

G2/M cellcycle arrest

MMAE disruptsmicrotubule network

Apoptosis


Long-Term Survival Analyses of an Eligibility and Preferred ArmsOngoing Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma

RChen, AK Gopal, SE Smith, SM Ansell, JD Rosenblatt, KJ Savage, JM Connors, A Engert, EK Larsen, EL Sievers, A Younes


Overall survival after treatment with brentuximab vedotin
Overall survival after treatment with Brentuximab vedotin Eligibility and Preferred Arms

  • Median observation time from 1st dose:

    • All patients = 29.5 months (range, 1.8 to 36.9)

    • CR patients = 29.1 months (range, 2.6 to 34.3)

  • 60/102 patients (59%) remain alive; median OS has not been reached (95% CI: 28.7, NE)

  • Estimated 24-month survival rate* = 65% (95% CI: 55, 74)


Overall survival by cycle 4 pet status
Overall Survival by Cycle 4 PET Status Eligibility and Preferred Arms


Conclusions
Conclusions Eligibility and Preferred Arms

After a median observation time of ~2.5 years from first brentuximab vedotin dose, 60 of 102 patients (59%) remain alive at last follow up

Median OS has not yet been reached; the estimated 24-mo survival rate was 65%

Improved OS strongly correlated with both:

Achievement of CR

Negative PET scan at Cycle 4

Prolonged OS was observed in patients with both long and short progression-free intervals after auto-SCT


What are we doing new for advanced stage hl

What are we doing new for Advanced-Stage HL Eligibility and Preferred Arms

How can we improve the cure rate and reduce the toxicity for advanced stage disease?


Frontline Therapy With Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced-Stage Hodgkin Lymphoma

Ansell SM, Connors JM, Park SI, O’Meara M, Younes A


Study design
Study Design ABVD or AVD in Patients with Newly Diagnosed Advanced-Stage Hodgkin Lymphoma

Phase I, multicenter, dose-escalation study

Major eligibility criteria

Treatment-naïve HL patients

Age ≥18 to ≤60 years

Stage IIA bulky disease or Stage IIB-IV disease

Treatment design

28-day cycles (up to 6 cycles) with dosing on Days 1 and 15

Dose escalation cohorts – I-6, II-13, III-6, IV-6, expansion-20

Cycle 3

Cycle 1

Cycle 2

Brentuximab Vedotin

A(B)VD

6 Cycles +/- XRT

0

2

4

6

8

10

12

Weeks

Ansell SM, et al. Blood. 2012;120: Abstract 798.


Response results at end of front line therapy
Response Results at End of Front-Line Therapy ABVD or AVD in Patients with Newly Diagnosed Advanced-Stage Hodgkin Lymphoma

  • Response results at end of front-line therapy:

    • ABVD cohorts: 21 of 22 CR (95%)

    • AVD cohorts: 24 of 25 CR (96%)

  • In addition, 1 patient withdrew consent and 3 patients were lost to follow-up prior to completion of front-line therapy and were not evaluable for response

Ansell SM, et al. Blood. 2012;120: Abstract 798.


Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002) ABVD or AVD in Patients with Newly Diagnosed Advanced-Stage Hodgkin Lymphoma


Study design hl stages iii iv ips 3 randomized phase iii trial
Study Design HL Stages III-IV IPS ≥ 3 Randomized Phase III Trial

Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)


Progression-Free Survival Trial

(Not a predefined study endpoint)

Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)


Treatment discontinuations for toxicity
Treatment Discontinuations for Toxicity Trial

Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)


Event-Free Survival Trial

Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)


Overall survival
Overall Survival Trial

Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)


Conclusions1
CONCLUSIONS Trial

EFS (primary endpoint) is similar between treatment arms. However, more progressions / relapses were observed with ABVD while early discontinuations were more frequent with BEACOPP

In this high-risk group, conventional dose escalation with BEACOPP 4+4 provides a better PFS compared to ABVD, yet not good enough to improve OS

Additional considerations (treatment burden & cost, fertility issues, risk of relapse, risk of salvage, immediate & late morbidities) may guide physician / patient decisions toward ABVD or BEACOPP, which currently may share the claim for “current standard of care”

Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)


Conclusions2
CONCLUSIONS Trial

A GENERAL SURVEY OF STUDIES COMPARING BEACOPP TO ABVD ALMOST ALL CONSISTENTLY SHOW A SUPERIOR PROGRESSION FREE SURVIVAL FOR BEACOPP BUT LONG TERM SURVIVAL SEEMS TO BE COMPARABLE DUE TO THE TOXICITY OF BEACOPP.

AS WITH LIMITED STAGE DISEASE, CAN INTERIM PET SCANS BE USED TO SELECT OUT THOSE PATIENTS NOTNEEDING MORE AGGRESSIVE THERAPY AND THEREBY AVOID ALL THE UNNECESSARY TOXICITY OF BEACOPP? IS GENETIC INSTABILITY ADVANCED BY DR DIEHL TRULY OPERATIVE EVEN AS EARLY AS (A PET SCAN AFTER) ONE CYCLE


3 cycles of ABVD without IFRT has an excellent outcome for favorable stage IA/IIA patients who are at the conclusion of treatment are PET neg.

Disease control may be slightly better for CMT as compared with CT (3%-7%), although a survival difference is unlikely although long-term effects of IF (reduced) RT are unknown.

BV + AVD results are comparable, if not superior, to ABVD for patients with stage III/IV HL. Phase III comparison has opened. BV has been shown effective in relapsing/refractory patients including those failing transplant. It is being incorporated into many strategies for the rx of ‘difficult’ HL pts.

The overall results with ABVD are at least equal to BEACOPP with less toxicity.

Interim PET scans may prove valuable in the rx strategies for HL.

SUMMARY


Acknowledgment

Wayne Tam, M.D. favorable stage IA/IIA patients who are at the conclusion of treatment are PET neg.

Amy Chadburn, M.D. (Northwestern)

Elizabeth Hyjek, M.D., Ph.D.

Acknowledgment

Clinical Research

Jia Ruan, M.D., Ph.D.

Richard Furman, M.D.

John P. Leonard, M.D.

Peter Martin, M.D.

Maureen Joyce, R.N.

Patricia Glenn, R.N.

Jamie Ketas

Jessica Hansen

Karen Weil

Jennifer O’Loughlin

Rebecca Elstrom, M.D. (Gen.)

Lale Kostakoglu, M.D. (Sinai)

Stanley Goldsmith, M.D.

Translational Core

Maureen Lane, Ph.D. (Cornell)

Maureen Ward

Biostatistician

Ken Chueng, Ph.D. (Columbia)

Madhu Mazumdar, Ph.D. (Cornell)

Lymphoma Research Foundation

ASCO Foundation (YIA, CDA)

NIH / NHLBI

Laboratory Research

Ari Milneck, M.D., Ph.D.(Cornell)

Katherine Hajjar, M.D. (Cornell)

Shahin Rafii, M.D. (Cornell)


THANK YOU FOR favorable stage IA/IIA patients who are at the conclusion of treatment are PET neg.

YOUR ATTENTION


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