T-cell replete allogeneic stem cell transplant for mantle cell lymphoma achieves durable disease control, including against TP53-mutated disease

Lew, Thomas E.; Cliff, Edward R Scheffer; Dickinson, Michael; Tam, Constantine S.; Seymour, John F.; Blombery, Piers; Bajel, Ashish; Ritchie, David; Khot, Amit

doi:10.1038/s41409-021-01418-3

Cited by 7 publications

(6 citation statements)

References 12 publications

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“…51 Since TP53 alterations are associated with resistance to chemotherapy, clinical trials using T-cell activating immunotherapies (CART or bispecific antibodies) or targeted therapies may be favoured over chemoimmunotherapy. [52][53][54] In addition, other trials are exploring chemotherapy-free induction regimens. The use of robust biomarkers of risk may make trial design, results and interpretation more straightforward.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of clinical parameters and biomarkers in older, untreated mantle cell lymphoma patients receiving bendamustine–rituximab

Ramsower,

Rosenthal,

Robetorye

et al. 2023

Br J Haematol

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SummaryMantle cell lymphoma (MCL) is clinically and biologically heterogeneous. While various prognostic features have been proposed, none currently impact therapy selection, particularly in older patients, for whom treatment is primarily dictated by age and comorbidities. Herein, we undertook a comprehensive comparison of clinicopathological features in a cohort of patients 60 years and older, uniformly treated with bendamustine and rituximab, with a median survival of >8 years. The strongest prognostic indicators in this cohort were a high‐risk call by a simplified MCL international prognostic index (s‐MIPI) (HR: 3.32, 95% CI: 1.65–6.68 compared to low risk), a high‐risk call by MCL35 (HR: 10.34, 95% CI: 2.37–45.20 compared to low risk) and blastoid cytology (HR: 4.21, 95% CR: 1.92–9.22 compared to classic). Patients called high risk by both the s‐MIPI and MCL35 had the most dismal prognosis (HR: 11.58, 95% CI: 4.10–32.72), while those with high risk by either had a moderate but clinically relevant prognosis (HR: 2.95, 95% CI: 1.49–5.82). A robust assay to assess proliferation, such as MCL35, along with stringent guidelines for cytological evaluation of MCL, in combination with MIPI, may be a strong path to risk‐stratify older MCL patients in future clinical trials.

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Section: Discussionmentioning

confidence: 99%

Evaluation of clinical parameters and biomarkers in older, untreated mantle cell lymphoma patients receiving bendamustine–rituximab

Ramsower,

Rosenthal,

Robetorye

et al. 2023

Br J Haematol

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“…First, it is a retrospective study that implies real world evidence but lacks homogeneity in terms of frontline or salvage therapies, supportive care strategies, and GVHD prophylaxis and management. We do not have some important diagnostic or prognostic information, such as molecular high-risk profiles or TP53 mutation status that could modify therapeutic decisions for allo-SCT candidates [ 38 , 39 ]. Addressing the abovementioned lack of some new strategies for GVHD prophylaxis such as cyclophosphamide post-allo-SCT, we could also mention a few patients receiving ibrutinib before and after allo-SCT, which may provide a benefit in terms of survival [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience

Gutiérrez¹,

Bento²,

Novelli³

et al. 2022

Cancers

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Allo-SCT is a curative option for selected patients with relapsed/refractory (R/R) MCL, but with significant NRM. We present the long-term results of patients receiving allo-SCT in Spain from March 1995 to February 2020. The primary endpoints were EFS, OS, and cumulative incidence (CI) of NRM, relapse, and GVHD. We included 135 patients, most (85%) receiving RIC. After a median follow-up of 68 months, 5-year EFS and OS were 47 and 50%, respectively. Overall and CR rates were 86 and 80%. The CI of relapse at 1 and 3 years were 7 and 12%. NRM at day 100 and 1 year were 17 and 32%. Previous ASCT and Grade 3–4 aGVHD were associated with a higher NRM. Grade 3–4 aGVHD, donor type (mismatch non-related), and the time-period 2006–2020 were independently related to worse EFS. Patients from 1995–2005 were younger, most from HLA-identical sibling donors, and were pretreated less. Our data confirmed that allo-SCT may be a curative option in R/R MCL with low a CI of relapse, although NRM is still high, being mainly secondary to aGVHD. The arrival of new, highly effective and low toxic immunotherapeutic or targeted therapies inevitably will relegate allo-SCT to those fit patients who fail these therapies, far away from the optimal timing of treatment.

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“…61 A more recent analysis of 32 patients undergoing alloSCT for MCL either in front-line or at relapse included 10 patients with TP53-mutated disease. 62 The 2-year PFS and OS for the TP53 mutated cases was 50% and 60% respectively, and the use of T-cell depletion was associated with inferior OS across all patients.…”

Section: Role Of Allogeneic Stem Cell Transplantation (Allosct) In Fi...mentioning

confidence: 90%

“…Overall, 2‐year PFS and OS were 61% and 78% respectively; however, TP53 mutations, deletions and p53 overexpression by IHC were aggregated, with outcomes specifically in TP53 ‐mutated patients not reported 61 . A more recent analysis of 32 patients undergoing alloSCT for MCL either in front‐line or at relapse included 10 patients with TP53 ‐mutated disease 62 . The 2‐year PFS and OS for the TP53 mutated cases was 50% and 60% respectively, and the use of T‐cell depletion was associated with inferior OS across all patients.…”

Section: Aggressive MCLmentioning

confidence: 99%

How I manage mantle cell lymphoma: indolent versus aggressive disease

et al. 2023

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Summary Mantle cell lymphoma (MCL) is a mature B‐cell lymphoma with a variable clinical course and historically poor prognosis. Management is challenging in part due to the heterogeneity of the disease course, with indolent and aggressive subtypes now well recognised. Indolent MCL is often characterised by a leukaemic presentation, SOX11 negativity and low proliferation index (Ki‐67). Aggressive MCL is characterised by rapid onset widespread lymphadenopathy, extra‐nodal involvement, blastoid or pleomorphic histology and high Ki‐67. Tumour protein p53 (TP53) aberrations in aggressive MCL are recognised with clear negative impact on survival. Until recently, trials have not addressed these specific subtypes separately. With the increasing availability of targeted novel agents and cellular therapies, the treatment landscape is constantly evolving. In this review, we describe the clinical presentation, biological factors, and specific management considerations of both indolent and aggressive MCL and discuss current and potential future evidence which may help move to a more personalised approach.

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T-cell replete allogeneic stem cell transplant for mantle cell lymphoma achieves durable disease control, including against TP53-mutated disease

Cited by 7 publications

References 12 publications

Evaluation of clinical parameters and biomarkers in older, untreated mantle cell lymphoma patients receiving bendamustine–rituximab

Evaluation of clinical parameters and biomarkers in older, untreated mantle cell lymphoma patients receiving bendamustine–rituximab

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience

How I manage mantle cell lymphoma: indolent versus aggressive disease

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