Treatment approaches to non-Hodgkin’s lymphoma in elderly patients Larry W. Kwak, M.D., Ph.D. Chairman, Department of Lymphoma/Myeloma Justin Distinguished Chair in Leukemia Research Co-Director, Center for Cancer Immunology Research MD Anderson Cancer Center
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TREATMENT OF NON-HIDGKIN'S LYMPHOMA IN ELDERLY PATIENTS
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Treatment approaches to non-Hodgkin’s lymphoma in
elderly patients
Larry W. Kwak, M.D., Ph.D.
Chairman, Department of Lymphoma/Myeloma
Justin Distinguished Chair in Leukemia Research
Co-Director, Center for Cancer Immunology Research
MD Anderson Cancer Center
Refractory/Relapsed DLBCL: Therapy for “Non-Transplant Candidates”
• Poor disease control and substantial morbidity.
• Goal is generally palliative • Gemcitabine based• Low dose oral chemotherapy• “hyperfractionated cytoxan”• Rituximab• Radiation
• New drugs
Novel Anti-CD20 MoAbs for Relapsed/Refractory Indolent Lymphoma
MoAb Phase Efficacy
Ofatumumab
I/IIDose (ORR): 300 mg (63%); 500 mg (33%);
700 mg (20%); 1000 mg (50%)
IIORR: 11%, 6-mo PFS in 116 pts with
rituximab-refractory FL
Veltuzumab I/II
IV administration: ORR: 44%, CR: 27%DOR in pts with FL: 19.7 mos
Subcutaneous administration: ORR: 53% CR: 20% in pts with indolent NHL
Ocrelizumab I/II ORR: 38%; PFS: 11.4 mos in pts with FL
Fong Clow, ScD9, Michelle Stevens-Brogan9, Lori Kunkel, MD9, Kristie A. Blum, MD10
1 Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; 2 Department of Haematology, Derriford Hospital, Plymouth, United Kingdom; 3 Division of Hematology-Oncology, Weill Cornell Medical
College, New York, NY; 4 John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ 5 Department Haemato-oncology, Barts Health NHS Trust, London, United Kingdom ; 6 Department of Medicine-
Hematology/Oncology, University of Wisconsin, Madison, WI; 7 Department of Haematology, Jagiellonian University, Krakow, Poland; 8 Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CA
9 Pharmacyclics, Inc., Sunnyvale, CA; 10 The Ohio State University, Columbus, OH
Best Response(Efficacy Population n=110, Median Follow-up 9.2 mo)
0
20
40
60
80
100
21 23 22
4449 46
CR PR
Per
cen
t o
f p
atie
nts
(%
)
Bortezomib-naïve(n=63)
Bortezomib-exposed(n=47)
Total(n=110)
66%72% 68%
Current Active Trials with Ibrutinib
Phase NCT# Combination DZ State Subtype
I 01704963 Single Agent Rel/Ref B-Cell NHL
I 01479852 Benda/Ritux Rel/Ref NHL
I 01569750 R-CHOP Untreated
LCL, MCL, Indolent
II 01599049 Single Agent Rel/Ref MCL (after Bortez)
II 01583902 Single Agent Rel/Ref SLL/CLL
II 01614821 Single Agent Rel/Ref Waldenstrom’s
III 01578707 vs Ofa Rel/Ref SLL/CLL
III 01611090 BR Rel/Ref SLL/CLL
LYMPH NODEMALIGNANT B-CELL
Class I PI3K Isoform
Cellular Expression Primary Physiological Role
Alpha Broad Insulin signaling and angiogenesis
Beta Broad Platelet function
Gamma Leukocytes Neutrophil and T-cell function
Delta LymphocytesB-cell signaling, development
and survival
PI3K Promotes Survival/Growth of Cancer Cells
Best On-Treatment Change in Tumor Size(ITT Analysis)
-100
-75
-25
0
-50*
+25
+50
+75
+100
MCL(N=21)
iNHL(N=30)
CLL(N=54)
Inevaluable (patients without a follow-up tumor assessment)
* Criterion for response [Cheson 2007, Hallek 2008]
% C
hang
e in
Lym
ph N
ode
Are
a
Single-Agent CAL-101 for R/R MCL, iNHL, and CLL: Best Tumor Volume Response
ORR with CAL-101 for R/R iNHL
Slide 24
Bortezomib (N=60)
Fostamatinib (Syk inhibitor) (N=25)
Lenalidomide (N=43)
PCI-32765 (Btk inhibitor) (N=20)
Rituximab (N=166)
Bendamustine (N=123)
CAL-101 (N=30)
12%
Prior Therapies(median)
4
4
3
3
2
2
3
12%
23%
30%
48%
75%
63%
ITT Response Rate [Exact Binomial 95% CI], %
Overall Response Rate Compared to Those with Other Drugs
PFS results are as good or better with CAL-101
• Grade 3-4 events were usually related to underlying disease or prior therapy
• Reversible Gr 3-4 ALT/AST elevations were not associated with increased bilirubin or decreases in liver synthetic function
• No obvious pattern of drug-related symptomatic adverse events
CAL-101 for R/R NHL: Cumulative Adverse Events
Fatigu
e
Neutropenia
Diarrhea
Pneumonia
Anorexia
ALT/A
ST0
20
40
60
80
100
10%8%8%
27%
6%10%
Grade 3-4 Adverse Events Occuring in 5%of Patients Regardless of Causality (N=51)
Adverse Event Type
Inci
denc
e, %
Department of Lymphoma/Myeloma Disease –specific Working Groups
N. FowlerF. SamaniegoS. NeelapuL. FayadL. Kwak
T cell lymphoma
Multiplemyeloma
D. WeberJ. ShahS. ThomasM. WangR. AlexanianQ. Yi
Michael Wang, M.D.Nathan Fowler, M.D.
Co-DirectorsLymphoma Clinical Research
Robert Orlowski, M.D., Ph.D.Director
Myeloma Clinical Research
BurkittHIV
BrainTesticular
M. Fanale N. Fowler
M. FanaleN. FowlerJ. ShahJ. Westin
Larry W. Kwak, M.D., Ph.D.Chairman, Lymphoma/Myeloma