mantle vedotincell lymphoma,Brentuximab

1. Dr CK Das
AIIMS
Update in Lymphoma

2. Phase II Trial of R-CHOP Plus Bortezomib
Induction Therapy Followed By Bortezomib
Maintenance for Previously Untreated Mantle Cell
Lymphoma: SWOG 0601
Abstract :149

3. Back ground
• Mantle cell lymphoma (MCL) :no consensus for the optimal
induction regimen.
• Bortezomib: mantle cell lymphoma who have received at least
one prior therapy
• Bortezomib: combination with chemotherapy may be
synergistic.
• maintenance rituximab after R-CHOP led to a survival benefit
in MCL
Kluin-Nelemans et al N Engl J Med. 2012 Aug 9;367(6):520-31

4. N=68
stage III, IV,
or bulky
stage II
MCL
6# R-CHOP
bortezomib
1.3 mg/m2
on D1/D4
Bortezomib
maintance
At least
SD
SalvagePD
• median age of 61
(range 36-85)
• 80% male
• 98% stage III-IV15%
bulky disease,
• 37% elevated LDH
bortezomib maintenance
therapy 1.3 mg/m2 days 1,
4, 8, and 11 every 3
months for 8 cycles

5. Results
• median follow-up time :5.9 years
• induction toxicities: 48% grade 4 hematologic toxicities,6% grade 4 non-
hematologic
• maintenance therapy:13% grade 3 non-hematologic toxicities.
• Grade 3 PN 8% -induction 2% -maintenance bortezomib, and there was no
grade 4 neuropathy.
Therapy 2-year PFS 2-year OS 5 years PFS 5 Year OS
VeR-CHOP 62%, 85%. 28% 66%.
R-CHOP 30%
MIPI Score low intermediate high
N 45% 43% 12%
2 yr PFS 72% 61% 25%

6. “Combination R-CHOP with bortezomib followed by maintenance
bortezomib doubled the historical 2 year PFS rate, with nearly
one third of patients achieving a PFS of 5 years or longer”

7. Abstract:148
Frontline Therapy with the RiBVD Regimen Elicits
High Clinical and Molecular Response Rates and
Long PFS in Elderly Patients Mantle Cell
Lymphoma (MCL); Final Results of a Prospective
Phase II Trial By the LYSA Group

8. Back ground
• RCHOP/21 cycles followed by Rituximab maintenance is considered
the standard of care for first line therapy in elderly MCL
• complete clinical (CR) and molecular responses (MR) to therapy
remain suboptimal(CR rate 30-35%, MR after 8 cycles 67 %).
• Regimen combining Rituximab and Bendamustine and more recently
proteasome inhibitor Bortezomib (Velcade®) with CHOP regimen
(VcR-CAP) demonstrated superior CR rates and PFS compared to R-
CHOP

9. • prospective phase II trial
• The primary objective :improve the median PFS by 6 months over the
current 18 months PFS obtained with RCHOP
• secondary objectives :prognostic impact of molecular and FDG-PET
responses on survival
• inclusion criteria: patients aged 65 or older with a diagnosis of MCL :
stage II-IV, PS < 3, no other neoplasm, no active HIV or HBV or HCV
infections, no renal or cardiac dysfunction, no diabetes.

10. Results
PR/CR/CRu4#RiBVD
2#RiBVD
Salvage
therapy
RQ-PCR
IGH VDJ
FDG-PET
Deauville
Score
>65 yr MCL
N =76
Median age 73
(64-83), sex ratio
M/F = 2 (49/25),
AAstage II/III-IV =
4/70, PS 0-1/2 =
63/11, MIPIscore
low/intermediate
/high= 3/19/50
CR/CRu :74% (n=55) PR rate
was 9% (n=7), 2 SD, 4 PD and
5 died .
MR rate>6 months on blood
83% (43/50) or bone
marrow 74 % (32/43).
At 24 months PFS was 69%
and OS 80%.
Toxicities :grade 3 or 4
neutropenia 51% and
thrombocytopenia 36% 3 or
4 fatigue (19%), neuropathy
(14%), cardiac (7%) or febrile
neutropenia (5%)
The MIPI score (high vs low/int) and blood MR after 6 cycles were the only two statistically prognostic factors for PFS and OS
The median follow-up is 21 months

11. “With 74% of CR/CRu, a 2 year PFS of 69% and
86% of patients achieving an MRD negative status
in the blood after 6 cycles, the RiBVD regimen is
identified as a highly effective, well tolerated, first
line treatment for elderly MCL patients”

12. Brentuximab Vedotin in Combination with
Bendamustine for Patients with Hodgkin
Lymphoma who are Relapsed or Refractory after
Frontline Therapy
• Abstract 293

13. Back ground
relapsed/refractory Hodgkin lymphoma salvage chemotherapy autologous stem cell
transplant
pts who CR with salvage chemotherapy prior to ASCT. Improved outcomes
standard salvage therapy(ICE/DHAP/MINE/mBEAM): Variable CR rates (19%-60%) and significant
toxicities
BENDAMUSTINE in HL:Relapsed refractory setting(ORR 52% CR 33%)
BRENTUXIMAB :Post ASCT relapsed Hodgkin lymphoma and relapsed refractory HL(ORR 73% with
a median duration of 6.7 months ,CR) rate 32 %)

14.  58% female
 median age of 35 yrs
relapsed disease
58% and primary
refractory
disease42%
 median of 13.1 m
post diagnosis
Auto
HSCT
N-24
BV 1.8 mg/kg
on D 1
+bendamustine
90 mg/m2 on
Days 1 and 2 of
3-week cycles
N=55
HL
median of 2 cycles
(range, 1-6)
median number of CD34+ : 4.3 x106
median of 2 apheresis sessions (range, 1-5)

15. results
• CR rate : 82% (28/34 pts evaluable for response)
• overall objective response rate (CR and PR) 94% (32/34 pts).
• The majority of CRs (24/28 pts) were achieved after 2 cycles of
combination therapy.
• Stem cell mobilization and collection was considered adequate in all
24 pts who underwent the procedure.
• The median number of CD34+ : 4.3 x106 (range, 1.7- 16.0 x106)
median of 2 apheresis sessions (range, 1-5)
• 0 SAEs, 1 treatment discontinuation, and 2 Grade 3 toxicity
(dyspnea (13%), flushing (13%), and chills (11%).)

16. • brentuximab +bendamustine :manageable safety profile
• The very high CR rate with combination treatment compares
favorably with historical data.
• “A promising approach for maximizing responses prior to ASCT in pts
with HL who are either relapsed or are refractory after frontline
therapy”

17. 371 Pediatric ALL-like Therapy in Adults with T-Cell
Lymphoblastic Lymphoma: Results of the GRAALL-
LYSA- LL03 Study

18. Back ground
• using paediatrics inspired protocols in Adult ALL yielded good results
–GRALLL-2003 study
• disease-free survival of about 65%-75% and an overall survival rate of
60%.

19. N=155
N=121
N=5
N=30
Total Relapse
N=34
Total death N=37
patients with high-
risk disease (defined
as need for a second-
induction salvage
course and/or CNS
disease

20. 131 T-LL patients
median age, 33 years; M/F
ratio 4
95% mediastinal
enlargement, 5% CNS
involvement,
119 patients (91%) reached
CR/CRu
30 patients needing a
salvage course
34 relapsed.
46 Death(37 relapse; 5
induction; 3 TRM and 1
other)
 Response evaluation was
based on CT scan
 5 years DFS 71% EFS 61% and
OS 66%,
 The lymphoma IPI-score had
no prognostic value
 increased serum LDH level
associated with a significant
decrease in EFS and OS
 need for a salvage course was
not associated with shorter
DFS in CR/CRu patients.
 4-gene risk
classifier (NOTCH1,
FBXW7, N/K-RAS
and PTEN status)
 high-risk genetic
profile was
predictive of
shorter EFS (HR =
14.3 [1.9 – 107.8])
 DFS (HR = 9.5 [1.2
– 74.3])
 OS (HR = 11.5 [1.5

21. • Good outcome in T-LL patients treated with a pediatric-inspired ALL
strategy.
• The NOTCH1/FBXW7/RAS/PTEN T-ALL risk classification is a strong
prognostic factor in these T-LL patients.
• Allogeneic SCT did not appear to significantly influence the outcome
of selected T-LL patients