Dr CK Das AIIMS Update in Lymphoma
Jul 16, 2015
Phase II Trial of R-CHOP Plus Bortezomib Induction Therapy Followed By Bortezomib
Maintenance for Previously Untreated Mantle Cell Lymphoma: SWOG 0601
Abstract :149
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
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
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%
“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”
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
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
• 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.
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, MIPIscorelow/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
“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”
Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy
• Abstract 293
Back ground
relapsed/refractory Hodgkin lymphoma salvage chemotherapy autologous stem cell transplantpts 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 %)
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
+bendamustine90 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)
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%).)
• 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 ptswith HL who are either relapsed or are refractory after frontline therapy”
371 Pediatric ALL-like Therapy in Adults with T-Cell Lymphoblastic Lymphoma: Results of the GRAALL-LYSA- LL03 Study
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%.
N=155
N=121
N=5
N=30
Total RelapseN=34
Total death N=37
patients with high-risk disease (defined as need for a second-
induction salvage course and/or CNS
disease
131 T-LL patients
median age, 33 years; M/F ratio 4
95% mediastinalenlargement, 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 – 87.5])
• 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