Oncology

Mantle Cell Lymphoma

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Autologous Stem Cell Transplantation for Mantle Cell Lymphoma in Different Treatment Settings

clinical topic updates by Bijal Shah, MD, MS
Overview

For several years, the hematologic community has been asking a lot of hard questions about the role of autologous stem cell transplant (ASCT) in patients with mantle cell lymphoma (MCL). The debate about transplants is based on both historical data and recent updates from the TRIANGLE and ECOG-ACRIN EA4151 trials reported at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2024.

“I think that the initial debate over the role of transplant in patients with MCL started after the results were reported from a European trial of CHOP or R-CHOP followed by ASCT or interferon alfa maintenance therapy.”
— Bijal Shah, MD, MS

I think that the initial debate over the role of transplant in patients with MCL started after the results were reported from a European trial of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP) followed by ASCT or interferon alfa maintenance therapy. In this trial, it was hard to see any added benefit of transplant because overall survival was not extended. However, the patients in this trial were not treated aggressively with cytarabine or a BTK inhibitor, so we thought that patients had a high burden of disease that the transplants could not overcome. That might be the reason we were not seeing a benefit to transplantation.

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At ASH 2024, updated data were presented from the TRIANGLE study comparing chemoimmunotherapy followed by ASCT with chemoimmunotherapy plus a BTK inhibitor and 2 years of BTK maintenance therapy with or without a transplant. There was no benefit to transplantation in patients treated maximally with chemoimmunotherapy, cytarabine, and a BTK inhibitor, and mortality increased with ASCT. However, in patients with high TP53 expression by immunohistochemistry, there was a benefit, although the 3 failure-free survival events that caused the survival curves to split occurred within approximately 6 months. Moreover, an analysis of patients from the Nordic MCL2 and MCL3 trials previously found that those with TP53 mutations did not benefit from chemoimmunotherapy followed by transplant, although these trials did not include BTK inhibitors. Regardless, with such small numbers in this subgroup analysis, there is not enough support to resume ASCTs for patients with TP53 mutations. The subgroup analysis of the blastoid variant of MCL from TRIANGLE was more interesting, even though there were only a handful of events. However, in this case, the events occurred mostly at the tail end of the curve, meaning that they cannot be attributed to study design but, rather, are truly treatment failures. So, for the TP53-unmutated blastoid variant of MCL, we really need to think harder, as there is potentially some benefit from this approach.

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The phase 3 ECOG-ACRIN EA4151 study was also presented at ASH 2024 as a late-breaking abstract and evaluated measurable residual disease (MRD)–guided transplantation independent of induction therapy. Patients who were MRD negative were randomized to receive a transplant with 3 years of rituximab maintenance or rituximab maintenance alone, while all patients with MRD positivity received a transplant with 3 years of rituximab. At the interim analysis, there was no added benefit of transplant, and, since there was no randomization for the MRD-positive arm, we cannot tell what its role is.

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Looking forward, I could see the treatment space evolving, and there could be a role for CAR T-cell therapy. A beautiful study recently looked at long-term follow-up after CAR T-cell immunotherapy in patients with lymphoma and multiple myeloma. Nonrelapse mortality was 10.6% in patients with MCL, and most of these deaths were attributed to infections. This is pretty good, since these are patients who had received multiple lines of therapy, and outcomes might be better in earlier lines of therapy when people’s immune systems are a little healthier.

References

Cordas Dos Santos DM, Tix T, Shouval R, et al. A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy. Nat Med. 2024;30(9):2667-2678. doi:10.1038/s41591-024-03084-6

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Dreyling M, Doorduijn J, Giné E, et al. Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. Lancet. 2024;403(10441):2293-2306. doi:10.1016/S0140-6736(24)00184-3

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Dreyling M, Doorduijn JK, Gine E, et al. Role of autologous stem cell transplantation in the context of ibrutinib-containing first-line treatment in younger patients with mantle cell lymphoma: results from the randomized TRIANGLE trial by the European MCL Network. Blood. 2024;144(suppl 1):240. doi:10.1182/blood-2024-200735

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Dreyling M, Lenz G, Hoster E, et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005;105(7):2677-2684. doi:10.1182/blood-2004-10-3883

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Eskelund CW, Dahl C, Hansen JW, et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017;130(17):1903-1910. doi:10.1182/blood-2017-04-779736

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Fenske TS, Wang XV, Till BG, et al. Lack of benefit of autologous hematopoietic cell transplantation (auto-HCT) in mantle cell lymphoma (MCL) patients (pts) in first complete remission (CR) with undetectable minimal residual disease (uMRD): initial report from the ECOG-ACRIN EA4151 phase 3 randomized trial. Blood. 2024;144(suppl 2):LBA-6. doi:10.1182/blood-2024-212973

Bijal Shah, MD, MS

Senior Member and Clinical Research Medical Director
Department of Malignant Hematology
Clinical Leader, Mantle Cell Lymphoma and Acute Lymphocytic Leukemia
Moffitt Cancer Center
Tampa, FL

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