Abstract
Carfilzomib plus rituximab, ifosfamide, carboplatin and etoposide (C-RICE) led to higher response, OS, and PFS in patients with transplant-eligible relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Author
person
Mody Amin
University at Buffalo, Buffalo, NY
info_outline
Mody Amin, Alex Niu, Kristopher Attwood, Anthony George, Farhan Azad, Jerry Wong, Grant Schofield, Dorothy C. Pan, Sheila N. J. Sait, Anne Marie W. Block, Eugene Przespolewski, Carolyn Connors, Joseph Demarco, Keryn Gauch, Nikolina Gjorgievski, Michael Johnson, Linda Manth, Kenneth McWhite, Matthew Joseph Cortese, Francisco J. Hernandez-Ilizaliturri
Full text
Authors
person
Mody Amin
University at Buffalo, Buffalo, NY
info_outline
Mody Amin, Alex Niu, Kristopher Attwood, Anthony George, Farhan Azad, Jerry Wong, Grant Schofield, Dorothy C. Pan, Sheila N. J. Sait, Anne Marie W. Block, Eugene Przespolewski, Carolyn Connors, Joseph Demarco, Keryn Gauch, Nikolina Gjorgievski, Michael Johnson, Linda Manth, Kenneth McWhite, Matthew Joseph Cortese, Francisco J. Hernandez-Ilizaliturri
Organizations
University at Buffalo, Buffalo, NY, Roswell Park Comprehensive Cancer Center, Buffalo, NY, Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, Roswell Park Comprehensive Cancer Center., Buffalo, NY, Roswell Park Cancer Institute, Buffalo, NY
Abstract Disclosures
Research Funding
No funding sources reported
Background:
The CORAL study highlighted the need to develop novel salvage regimens for R/Rr/r DLBCL previously treated with R+CHOP. Overall response rate (ORR) to second line immuno-chemotherapy was 51% with a 3-year progression free survival (PFS) of 30% following high-dose chemotherapy and autologous stem cell support (HDC-ASCS). Optimal disease control (complete remission [CR] or partial remission [PR]) prior to HDC-ADCS and more recently to chimeric antigen receptor T-cell therapy (CAR T), correlates with improved outcomes. Dysregulation of Bcl-2 family members has been associated with acquired resistance to rituximab and chemotherapy which we have previously shown may be mitigated by co-treatment with proteasome inhibition in pre-clinical model. Subsequently, we conducted a Phase I/II clinical trial evaluating the safety and efficacy of CRICE as salvage therapy for R/R DLBCL (Blood Adv. 2023 7:1146-1155).
Methods:
Here we retrospectively compared the clinical outcomes of R/R DLBCL patients treated with CRICE (N=28) versus RICE (N=38) on our prior clinical trial (NCT01959698). Demographic, clinical, and pathological characteristics were collected for both groups (Table). Study endpoints consisted of differences in overall response rate (ORR), CR/PR rates, median progression free survival (PFS) and overall survival (OS) between the two cohorts.
Results:
The addition of Carfilzomib to RICE resulted in improved clinical outcomes. A higher ORR (92.9 vs 76.3, P=0.073) and CR rates (82.1 vs. 44.7, P=0.002) were observed in CRICE vs. RICE treated patients. Multivariate analysis confirmed the higher CR rates in CRICE vs. RICE when adjusted by DLBCL subtype (GCB vs. nNon-GCB, P=0.003). More CRICE patients proceeded to HDC-ASCS (52.6% vs. 47.4%, P=0.618). The 3yr PFS rate was higher in CRICE (54%, 32-72%) vs. RICE treated patients (35%, 19-51%). While the median PFS was longer in CRICE treated patients 36.8m (0.8, 73.2) vs. 3.2m (0.5, 54.2) (RICE), it did not reach statistical significance (P=0.714). No differences in OS were observed between CRICE & RICE patients, median OS 67.3m vs. 71.8m.
Conclusions:
The CRICE outcomes were more striking in patients with non-GCB r/r DLBCL (ORR 85%, mPFS and OS not reached). CRICE led to high CR rates and longer PFS among r/r DLBCL patients, especially in non-GCB DLBCL patients. CRICE could be an attractive regimen to achieve disease control in r/r DLBCL patients undergoing consolidation therapy with HDC-ASCT or CAR T-cell therapy.
Patient characteristics.
RICE
C-RICE
P value
Male/Female
22/16
15/13
NS
Median Age
59yr
59yrs
NS
Stage
I
II
III
IV
5
7
3
23
2
4
9
12
NS
IPI score
Low (0-1)
Low-Intermediate (2)
High-Intermediate (3)
High (4-5)
12
4
15
7
6
10
7
6
NS
GBC
Non-GCN
9 (23.7%)
29 (76.3%)
15 (53.6%)
13 (46.4%)
0.019
Double hit status
4
5
NS
Refractory
Relapse
21
15
10
17
NS
Clinical status
Clinical
4 organizations
6 drugs
7 targets
Drug
CarfilzomibDrug
CRICEDrug
RICEDrug
rituximabDrug
chemotherapyTarget
chemotherapyTarget
Bcl-2 family membersTarget
ProteasomeTarget
rituximabTarget
CarfilzomibTarget
CD20+Target
BCL-2 family proteinsOrganization
Roswell Park Comprehensive Cancer CenterOrganization
Roswell Park Cancer Institute