• O can safely be used in combination with chemotherapy and in maintenance after ASCT as frontline therapy in patients with MCL.

  • O provides better disease control than R without additional toxicity in the MCL.

Abstract

Obinutuzumab (O) and rituximab (R) are 2 CD antibodies that have never been compared in a prospective randomized trial of mantle cell lymphoma (MCL). Herein, we report the long-term outcome of the LyMa-101 trial, in which newly diagnosed patients with MCL were treated with chemotherapy plus O before transplantation, followed by O maintenance (O group). We then compared these patients with those treated with the same treatment design with R instead of O (R group). A propensity score matching (PSM) was used to compare the 2 populations (O vs R groups) in terms of measurable residual disease (MRD) at the end of induction (EOI), progression-free survival (PFS), and overall survival (OS). In LyMa-101, the estimated 5-year PFS and OS after inclusion (n = 85) were 83.4% (95% confidence interval [CI], 73.5-89.8) and 86.9% (95% CI, 77.6-92.5), respectively. At EOI, patients treated in the O group had more frequent bone marrow MRD negativity than those treated in the R group (83.1% vs 63.4%; χ2, P = .007). PSM resulted in 2 sets of 82 patients with comparable characteristics at inclusion. From treatment initiation, the O group had a longer estimated 5-year PFS (P = .029; 82.8% vs 66.6%; hazard ratio [HR], 1.99; 95% confidence interval (CI), 1.05-3.76) and OS (P = .039; 86.4% vs 71.4%; HR, 2.08; 95% CI, 1.01-4.16) compared with the R group. Causes of death were comparable in the 2 groups, the most common cause being lymphoma. O before transplantation and in maintenance provides better disease control and enhances PFS and OS compared with R in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT00921414 and NCT02896582.

1.
Le Gouill
S
,
Thieblemont
C
,
Oberic
L
, et al
.
Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma
.
N Engl J Med
.
2017
;
377
(
13
):
1250
-
1260
.
2.
Bond
D
,
Switchenko
JM
,
Maddocks
KJ
, et al
.
Outcomes following early relapse in patients with mantle cell lymphoma [abstract]
.
Blood
.
2019
;
134
(
suppl 1
):
753
-
754
.
3.
Sarkozy
C
,
Thieblemont
C
,
Oberic
L
, et al
.
Very long-term follow-up of rituximab maintenance in young patients with mantle cell lymphoma included in the LYMA trial, a LYSA study
.
Hematol Oncol
.
2023
;
41
(
S2
):
151
-
152
.
4.
Dreyling
M
,
Doorduijn
JK
,
Gine
E
, et al
.
Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: results from the randomized triangle trial by the European MCL Network [abstract]
.
Blood
.
2022
;
140
(
suppl 1
):
1
-
3
.
5.
Marcus
R
,
Davies
A
,
Ando
K
, et al
.
Obinutuzumab for the first-line treatment of follicular lymphoma
.
N Engl J Med
.
2017
;
377
(
14
):
1331
-
1344
.
6.
Sehn
LH
,
Martelli
M
,
Trněný
M
, et al
.
A randomized, open-label, phase III study of obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-Cell lymphoma: final analysis of GOYA
.
J Hematol Oncol
.
2020
;
13
:
71
.
7.
Chiron
D
,
Bellanger
C
,
Papin
A
, et al
.
Rational targeted therapies to overcome microenvironment-dependent expansion of mantle cell lymphoma
.
Blood
.
2016
;
128
(
24
):
2808
-
2818
.
8.
Le Gouill
S
,
Beldi-Ferchiou
A
,
Alcantara
M
, et al
.
Molecular response after obinutuzumab plus high-dose cytarabine induction for transplant-eligible patients with untreated mantle cell lymphoma (LyMa-101): a phase 2 trial of the LYSA group
.
Lancet Haematol
.
2020
;
7
(
11
):
e798
-
e807
.
9.
Kluin-Nelemans
HC
,
Hoster
E
,
Hermine
O
, et al
.
Treatment of older patients with mantle cell lymphoma (MCL): long-term follow-up of the randomized European MCL elderly trial
.
J Clin Oncol
.
2020
;
38
(
3
):
248
-
256
.
10.
Austin
PC
.
The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments
.
Stat Med
.
2014
;
33
(
7
):
1242
-
1258
.
11.
Cheson
BD
,
Horning
SJ
,
Coiffier
B
, et al
.
Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas
.
J Clin Oncol
.
1999 Apr
;
17
(
4
):
1244
. Erratum in: J Clin Oncol. 2000;18(11):2351.
12.
Ladetto
M
,
Cortelazzo
S
,
Ferrero
S
, et al
.
Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial
.
Lancet Haematol
.
2021
;
8
(
1
):
e34
-
e44
.
13.
Hermine
O
,
Jiang
L
,
Walewski
J
, et al
.
High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: long-term follow-up of the randomized mantle cell lymphoma younger trial of the European Mantle Cell Lymphoma Network
.
J Clin Oncol
.
2023
;
41
(
3
):
479
-
484
.
14.
Seymour
JF
,
Marcus
R
,
Davies
A
, et al
.
Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression
.
Haematologica
.
2019
;
104
(
6
):
1202
-
12088
.
15.
Tessoulin
B
,
Chiron
D
,
Thieblemont
C
, et al
.
Oxaliplatin before autologous transplantation in combination with high-dose cytarabine and rituximab provides longer disease control than cisplatin or carboplatin in patients with mantle-cell lymphoma: results from the LyMA prospective trial
.
Bone Marrow Transplant
.
2021
;
56
(
7
):
1700
-
1709
.
16.
Le Gouill
S
,
Morschhauser
F
,
Chiron
D
, et al
.
Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial
.
Blood
.
2021
;
137
(
7
):
877
-
887
.
17.
Wang
M
,
Robak
T
,
Maddocks
KJ
, et al
.
Acalabrutinib plus venetoclax and rituximab in patients with treatment-naïve (TN) mantle cell lymphoma (MCL): 2-year safety and efficacy analysis [abstract]
.
Blood
.
2022
;
140
(
suppl 1
):
6477
-
6479
.
18.
Kumar
A
,
Soumerai
JD
,
Abramson
JS
, et al
.
Preliminary safety and efficacy from a multicenter, investigator-initiated phase II study in untreated TP53 mutant mantle cell lymphoma with zanubrutinib, obinutuzumab, and venetoclax (BOVen) [abstract]
.
Blood
.
2021
;
138
(
suppl 1
). 3540.
You do not currently have access to this content.
Sign in via your Institution