Up to dates on Lymphoma as a part of 2015 ASCO Annual Meeting.

1. ASCO 2015 LYMPHOMA UPDATE
Dr Chandan

2. Lenalidomide in combination with rituximab for
relapsed or refractory mantel cell lymphoma:
Updated analysis of a phase 2 trial.
• Yucai Wang, Maria Lourdes Dela Rosa, Shouhao Zhou, Maria Badillo, Alicia Addison, Liang Zhang,
Hun Ju Lee, Jorge Enrique Romaguera, Michael Wang; Rutgers New Jersey Medical School,
Newark, NJ; The University of Texas MD Anderson Cancer Center, Houston, TX
J Clin Oncol 33, 2015 (suppl; abstr 8542)

3. Study characteristic
• Relapsed refractory MCL
• single arm phase 1/2 trial
• Lenalidomide 20 mg daily days 1-21 of each 28-day cycle
• Rituximab 375 mg/m2 weekly during the first cycle only.
• Treatment was continued until disease progression, stem-cell
transplantation, or severe toxicity.
• The primary endpoint :ORR and the secondary endpoint OS.
• Analysis by intention to treat.

4. Result• 46 patients
• The median age was 66.5 (range 46-85).
• Median number of prior lines of therapy was 2 (range 1-4).
• At a median follow up of 24.7 months (range 1.2-96.1),
• CR: 16 (34.8%) PR: 10 (21.7%) ,ORR of 56.5%. SD: 10 (21.7%) patients
• ORR was independent of age, gender, number of prior lines of therapy and.
• Median time to response was 1.8 months (range 1.6-7.7). Median duration of response was 20.9
months (95% CI 10.9-NR).
• The median PFS was 14.1 months (95% CI 8.2-26.7), The 12- and 24-month PFS rates were 53.1%
and 39.9%, respectively
• The median OS was 24.6 months (95% CI 16.8-33.7) The 1-, 2- and 5-year OS rates were 82.6%,
52.2% and 26.1%, respectively.
• Lower Ki-67 at registration ( < 50%) and fewer prior lines of therapy ( < 2) were predictive of
better PFS (HR = 0.242, 95% CI 0.070-0.715, P = 0.012; and HR = 0.245, 95% CI = 0.071-0.841, P =
0.025) and OS (HR = 0.267, 95% CI 0.110-0.648, P = 0.003; and HR = 0.363, 95% CI = 0.147-0.896, P
= 0.028).

5. “Lenalidomide plus rituximab is efficacious in treating
R/R MCL with good ORR (55%) with durable response
(>20 month)”

6. Updated results of a phase II trial of brentuximab
vedotin combined with R-CHOP in frontline treatment
of patients with high-intermediate/high-risk diffuse
large B-cell lymphoma (DLBCL).
Nancy L. Bartlett, Charles M. Farber, Christopher A. Yasenchak, Stephen Maxted Ansell, Ranjana H. Advani, Mark H. Knapp, Luis Fayad, Kathryn S.
Kolibaba, Dipti Patel-Donnelly, Mahesh Seetharam, Habte Aragaw Yimer, Thomas John Manley, John M. Burke, Beata Holkova, L. Elizabeth Budde, Ahmad
Sami Halwani; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO; Hematology-Oncology Associates of Northern
New Jersey and Pennsylvania Carol G. Simon Cancer Center/US Oncology Research, Morristown, NJ; Willamette Valley Cancer Institute and Research
Center/US Oncology Research, Springfield, OR; Mayo Clinic, Rochester, MN; Stanford University Medical Center, Stanford, CA; Mid-Ohio
Oncology/Hematology Inc., Columbus, OH; The University of Texas MD Anderson Cancer Center, Houston, TX; Northwest Cancer Specialists/US Oncology
Research, Vancouver, WA; Virginia Cancer Specialists/US Oncology Research, Fairfax, VA; Arizona Oncology Associates/US Oncology Research, Phoenix,
AZ; Texas Oncology-Tyler/US Oncology Research, Tyler, TX; Seattle Genetics, Inc., Bothell, WA; Rocky Mountain Cancer Centers/US Oncology Research,
Aurora, CO; Virginia Commonwealth University Massey Cancer Center, Richmond, VA; City of Hope National Medical Center, Duarte, CA; University of
Utah Huntsman Cancer Institute, Salt Lake City, UT

7. Study characteristic
• 53 pt: 6# BV+R-CHOP: 1.2 or 1.8 mg/kg BV q3 wks
• Inclusion criteria IPI>3–5 or age-adjusted IPI (aaIPI) scores of 2–3
(high-intermediate/high risk).
• 62% were high-intermediate risk (IPI 3, aaIPI 2) ,38% were high risk
(IPI 4-5, aaIPI 3).
• 70%:stage IV disease
• 28% had an ECOG PS 2.
• Due to an increased rate of G3 neuropathy seen early in the 1.8
mg/kg BV+RCHOP arm (30% vs 8%), treatment continue at 1.2 mg/kg
BV+R-CHOP.

8. Result
• ORR: 97% with PET CMR 80%
• CR: 1.2 mg/kg BV+RCHOP 86% 1.8 mg/kg BV+R-CHOP, 75%
• CD30+ pts (n=13): CR 92% vs CD30– pts (n = 16) CR 69%.
• CR rates were similar between ABC and GCB subtypes.
• Treatment-emergent adverse events (AEs) occurred in 96%
• ≥ G3 febrile neutropenia (27%), and anemia (24%).
• AEs of neuropathy (mostly G1/2) occurred in 55% (38%, 1.2 mg/kg
BV+R-CHOP; 77%, 1.8 mg/kg BV+RCHOP).

9. “BV+R-CHOP has encouraging activity in frontline high-
intermediate/high risk DLBCL; with CR rate in CD30+ pts
was higher than in CD30– pts.
In combination with R-CHOP, BV is better tolerated at
1.2 mg/kg than 1.8 mg/kg due to reduced neuropathy.”
“

10. Effect of prednisone and rituximab prephase on
early toxicity in older DLBCL patients (pts) receiving
RCHOP within a NHL specific comprehensive
geriatric assessment (CGA) trial.
• Colette Ngozi Owens, Augustine Iannotta, John F. Gerecitano, Matthew J. Matasar, Ariela Noy, Craig H.
Moskowitz, Pamela Drullinsky, Maria Lia Palomba, David J. Straus, Steven M. Horwitz, Andrew David
Zelenetz, Carol S. Portlock, Anita Kumar, Paul A. Hamlin; Memorial Sloan Kettering Cancer Center, New York,
NY; Memorial Sloan Kettering Cancer Center, Englewood, NJ; Memorial Sloan Kettering Cancer Center,
Rockville Centre, NY

11. Study characteristics
• Eligible pts (n = 30) de novo DLBCL/tDLBCL,
• age ≥ 70 yrs or ≥ 60 yrs with KPS < 80%, and planned RCHOP-like
therapy for 2+ cycles.
• CGA :CARG +CRASH scores as largely self administered assessments.
CGA was assessed at baseline, post pre-phase, with each cycle, and at
end-of-therapy.
• Pre-phase : Pred 50-100mg x 5-10 days + R 375mg/m2 x1 day
completed in the 14 days pre-RCHOP.
• The study is powered to show a 15% change in CGA risk score, with
secondary endpoints of toxicity, TRM, PFS/OS.

12. Cancer and Aging Research Group - Chemo
Toxicity Risk Score

13. Result
• median age 75 (range 65-85), female 59%
• DLBCL 87%, Stage III/IV 60%, aaIPI high-int/high 57%
• cell of origin GC/non-GC 55%/45%
• median ki67 70% (range 60-90%).
• 97 % completed pre-phase and 2+ cycles of chemotherapy.
• Median followup is 6m (range 1-18m) with 28/30 pts alive.

14. RESULT
BASELINE POST PREPHASE
KPS median 70% 80%
CGA predicted risk of G3+ toxicity 65%(range 32-89%) Toxicity risk score 31% (9/29) pts, mean 16% risk
reduction for G3+ toxicity
non-heme grade 3+ events were 41% and
heme G4+ events 16%.
no reported TLS or early TRM (n = 30

15. “A pre-phase intervention of Pred and R may
mitigate early toxicity, resulting in improved KPS and CGA
risk score, with no TLS or early TRM”

16. GADOLIN: Primary results from a phase III study of
obinutuzumab plus bendamustine compared with
bendamustine alone in patients with rituximab-
refractory indolent non-Hodgkin lymphoma
• Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail,
Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch,
Guenter Fingerle-Rowson, Bruce D. Cheson; BC Cancer Agency, Vancouver, BC, Canada; Department of Oncology, Cross Cancer Institute,
University of Alberta, Edmonton, AB, Canada; Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk
University, Brno, Czech Republic; Department of Medical Oncology, BC Cancer Agency, Kelowna, BC, Canada; First Faculty of Medicine,
Charles University General Hospital, Prague, Czech Republic; Department of Haematology, CHU Haut-Lévèque, Pessac, France; The
University of Texas MD Anderson Cancer Center, Houston, TX; Department of Oncology-Hematology and Cell Therapy, University Hospital,
Poitiers, France; Fred Hutchinson Cancer Research Center, Seattle, WA; Hospices Civils de Lyon, Université Claude Bernard, Pierre Bénite,
France; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Northern
Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Hematology, Erasmus MC
Cancer Insitute, Rotterdam, Netherlands; Biostatistics, F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom; Pharma Development
Oncology, F. Hoffmann-La Roche, Basel, Switzerland; Georgetown University Hospital, Washington, DC

17. Study characteristics
• GADOLIN (NCT01059630) is a phase III open label study I
• Primary endpoint was PFS assessed by an independent radiology
facility (IRF), with 80% power to detect 43% improvement in median
PFS.
CD20+Rituximab
Refractory
396 pts
Bendamustine 120 mg/m2
D1/2+G 1000 mg d1, 8, 15
#1,
d1 #2-6 N=194
PD- BSC
Any response: G every 2
mo for up to 2 yrs
Bendamustine 120 mg/m2
D1/2+
N=198

18. Result
• Median age was 63 yrs and pts had a median of 2 prior therapies
• Median PFS was 14 mo for B and 29 mo for GB (HR 0.52, 95% CI 0.39–0.70;
p < 0.0001). OS Not reached
•
• There were no significant differences in IRF-assessed ORR (63.0% B vs
69.1% GB) or CR (12.2% B vs 11.2% GB) at end of induction
• fewer Grade ≥ 3 adverse events with B than GB (62.1% B vs 68% GB),
notably neutropenia (26.3% B vs 33.0% GB) and infusion-related reactions
(3.5% B vs 8.8% GB)

19. “First randomized evidence of benefit for a novel
aCD20 mAb in Rit-Ref iNHL”
“G combined with B (90 mg/m2) followed by G
maintenance significantly improved PFS vs B alone (120
mg/m2) in Rit-Ref iNHL.”