All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.
Introducing
Now you can personalise
your Lymphoma Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The Lymphoma & CLL Hub is an independent medical education platform, sponsored by Beigene and Roche, and supported through educational grants from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Pfizer, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC View funders.
Bookmark this article
Mantle cell lymphoma (MCL) remains an incurable disease. MCL accounts for 5–7% of all malignant lymphomas, and its incidence rates are increasing. Despite recent advances, patients with refractory disease or those who relapse following induction therapy have limited treatment options, and their disease is considered hard to treat. Younger patients with MCL are believed to have improved outcomes in the long term, however, systematic studies in this population are rare.
In the retrospective MANTLE-FIRST study, Carlo Visco et al. investigated outcomes in younger patients with MCL who relapsed for the first time or were refractory, to assess their second-line treatment options. They recently published their results in Leukemia.1
The total number of patients with R/R MCL was 261, with a median age of 58 years (range, 19–70) and more than half (59%) of patients younger than 60 years. Almost half (49%) of patients had early PD, and 36% had a high MCL International Prognostic Index (MIPI) score. Baseline characteristics of the patients are provided in Table 1.
Table 1. Patient characteristics among treatment groups1
allo-SCT, allogeneic stem cell transplantation; auto-SCT, autologous stem cell transplantation; B, bendamustine; BAC, bendamustine + cytarabine; CHOP, cyclophosphamide + doxorubicin + vincristine + prednisone; DHAP, dexamethasone + high dose cytarabine + cisplatin; HDS, high dose sequential therapy; HyperCVAD, cyclophosphamide + vincristine + doxorubicin + dexamethasone; MA, methotrexate + cytarabine; PD, progression of disease; R, rituximab. |
|||||
Characteristics, n (%) |
Study population (N = 261) |
R-BAC (n = 76) |
R-B (n = 54) |
Ibrutinib (n =50) |
Others (n = 81) |
---|---|---|---|---|---|
Blastoid or pleomorphic disease |
59 (24)
|
17 (24) |
13 (25) |
20 (20) |
19 (27) |
Early PD Late PD |
127 (49) 134 (51) |
31 (41) 45 (59) |
22 (41) 32 (59) |
27 (54) 23 (46) |
47 (58) 34 (42) |
Refractory |
37 (14) |
10 (13) |
5 (9) |
8 (16) |
14 (17) |
Frontline treatment |
|||||
R-HyperCVAD/MA R-CHOP/R-DHAP + auto-SCT Nordic regimen/R-HDS |
64 (24) 85 (33) 112 (43) |
30 (39) 16 (22) 30 (39) |
7 (13) 22 (41) 25 (46) |
3 (6) 23 (46) 24 (48) |
24 (30) 24 (30) 33 (40) |
Further transplantation in subsequent remission, n (%) |
|||||
Auto-SCT Allo-SCT |
18 (7) 59 (23) |
(6) (27) |
(7) (16) |
(2) (29) |
(10) (22) |
ORR to second-line therapies was 59% in all patients, and the highest ORRs were achieved with R-BAC (73%), compared to the lowest ORR with Others (37%). Overall CR rate was 44%, while age- and early/late PD-adjusted CR rates were highest with R-BAC (63%), followed by R-B (43%; odds ratio [OR], 0.43; 95% CI, 0.20–0.93; p = 0.033), ibrutinib (38%; OR, 0.36; 95% CI, 0.16–0.81; p = 0.013), and Others (30%; OR, 0.27; 95% CI, 0.13–0.56; p < 0.0001). While patients with early PD had similar CR rates with ibrutinib (31%) and R-BAC (32%), CR in patients with late PD was highest with R-BAC (85%).
Median OS-2 and PFS-2 for the whole study population were 36 and 13 months, respectively. Patients receiving other regimens (the ‘Others’ group) had a shorter median OS-2 (22.3 months; 95% CI, 13.3–37.8) compared with other second-line options. Treatment with Others was associated with a significantly shorter OS-2 versus ibrutinib (HR, 2.07; 95% CI, 1.14–3.74; p = 0.016). PFS-2 for the respective treatment groups is outlined in Table 2.
Table 2. PFS-2 among study groups1
B, bendamustine; BAC, bendamustine + cytarabine; PFS, progression-free survival; R, rituximab. PFS-2 was defined as time until lymphoma relapse or progression after second-line therapy, or death due to any cause. |
|||||
Outcome |
Study population (N = 261) |
R-BAC (n = 76) |
R-B (n = 54) |
Ibrutinib (n =50) |
Others (n = 81) |
---|---|---|---|---|---|
Median PFS-2, months |
13 |
25 |
13 |
24 |
7 |
Early PD was another factor that had a negative impact on both OS and PFS (see Table 3).
Survival curves demonstrated that patients with early PD were at higher risk of death and disease progression compared with those who experienced late progression (see Table 3).
Survival data among study groups by timepoint of disease progression are presented in Table 3.
Table 3. OS-2 and PFS-2 by time of disease progression and second-line therapy option1
B, bendamustine; BAC, bendamustine + cytarabine; CI, confidence interval; NR, not reached; OS, overall survival; PD, progression of disease; PFS, progression-free survival; R, rituximab. OS-2 was defined as time until death due to any cause, censored at last contact in patients surviving the follow-up period. PFS-2 was defined as time until lymphoma relapse or progression after second-line therapy, or death due to any cause. |
||||
|
Median OS-2, months (95% CI) |
Median PFS-2, months (95% CI) |
||
---|---|---|---|---|
Early PD |
Late PD |
Early PD |
Late PD |
|
R-BAC
|
10.3 (7.7–22.1) p = 0.02 |
NR (34.1–NR) |
6.5 (3.8–18.9) |
52.4 (24.7–NR) |
R-B
|
11.9 (5.3–28.7) p = 0.02 |
73.5 (46.2–NR) |
5.5 (1.9–9.6) |
31.7 (12.6–NR) |
Ibrutinib
|
29.7 (15.7–NR) |
NR (28.1–NR) |
9.9 (4.9–NR) |
44.9 (18.9–NR) |
Others
|
12.8 (6.9–16.6) p = 0.02 |
40.7 (22.3–76.3) |
5.5 (2.7–9.0) |
12.5 (5.49–26.3) |
Patients who were refractory to frontline induction therapy had a median PFS-2 of 3.5 months (95% CI, 2.1–9.3), and a median OS-2 of 7.9 months (95% CI, 4.4–15.7). Ibrutinib was associated with better survival outcomes in these patients (OS-2, 15.7 months; PFS-2, 9.3 months), however, the difference was not statistically significant.
The MANTLE-FIRST study appears to demonstrate that ibrutinib and R-BAC as second-line therapy in younger patients with MCL yield the best survival outcomes, while ORRs were best with R-BAC. This study also confirmed early PD as an independent variable influencing outcome. In terms of PFS-2 and OS-2, the study concluded that ibrutinib therapy was significantly associated with better OS and PFS in patients with early PD, while ibrutinib, R-B, and R-BAC were equally effective in patients with late PD. However, the authors suggest that further evaluation of best treatment options is needed in patients with late PD.
Limitations of this study include the lack of central pathologic review and the use of different allo-SCT guidelines due to the multi-center design. The selection bias that may have arisen from the retrospective study design was another limitation.
Understanding your specialty helps us to deliver the most relevant and engaging content.
Please spare a moment to share yours.
Please select or type your specialty
Your opinion matters
Subscribe to get the best content related to lymphoma & CLL delivered to your inbox