Autologous Hematopoietic Stem Cell Transplant Produces Enduring Responses in MCL

Autologous hematopoietic stem cell transplantation (HSCT) for the treatment of mantle cell lymphoma (MCL) has long term efficacy, drawing into question the use of antibody maintenance, high-dose cytarabine, and targeted treatments which tends to have a reduction in efficacy over time, according to a post hoc analysis published in The Lancet Hematology.

The current standard of care for MTC) is autologous HSCT, which has proven high response and progression-free survival (PFS) rates over the past 20 years. HSCT as the standard of care for MCL was established by a 1996 trial that compared HSCT to interferon alfa maintenance after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like induction therapy without or with rituximab (R-CHOP). For those who received HSCT, PFS was significantly longer than for those who received HSCT than for those who received CHOP or R-CHOP. However, overall survival (OS) was not significantly different between the 2 groups.

However, in the years since this study, treatment options for patients with MCL have progressed greatly. For example, the use of rituximab in both induction and maintenance therapy along with other targeted drugs has greatly improved both response rates, PFS, and OS.

The post-hoc analysis looked at the long-term outcomes of patients in the initial phase 3 study. The study recruited 292 individuals, 269 of which were randomized into 1 of 2 groups. The control group, where patients received interferon alfa, enrolled 135 participants. The experimental group, where patients received HSCT, enrolled 134 participants. The Primary end point for the post-hoc analysis was PFS from end of induction until progression or death among patients who had remission.

Of the patients in the control arm, 114 were evaluated for efficacy. Thirty-three patients did not achieve remission. Of those, 21 achieved stable disease, 7 had early progressive disease, 1 had an early death, 2 were not documented, and 2 were not restaged. After induction, 81 remissions were reported.

In the experimental arm, 118 patients were evaluated for efficacy, with 93 patients achieving remission after induction. Of the 25 patients who did not achieve remission, 16 had stable disease, and 9 had early progressive disease.

Eighty-one patients in the control group and 93 patients in the experimental group were included in the post-hoc analysis. In the control arm, 74% of patients were male and 81% of patients were male in experimental arm. The most common stage of disease in both arms was IV, with 83% of patients in the control arm with stage IV disease and 82% of patients in the experimental arm. A minority of patients in both the control (31%) and the experimental (28%) had elevated serum LDH concentration. B symptoms were present in 44% of patients in the control arm and 37% of patients in experimental arm. In the control arm, 51% of patients had an ECOG score of 1, 42% had a score of 0, and 7% had a score of 2. In the experimental arm, 56% of patients had an ECOG score of 1, 41% had a score of 0, and 3% had a score of 2. The majority of patients in both arms had an MCL international prognostic index rating of low risk (control, 68%; experimental 77%). 

For both arms, CHOP was the most common induction treatment. In the control arm, 53% of patients received chop compared with 48% of patients in the experimental arm. In the control arm, 33% of patients received R-CHOP compared with 44% in the experimental arm. The remaining patients in both arms received a CHOP-like chemotherapy regimen. At the end of induction, 23% of patients in the control arm had a complete remission compared with 34% of patients in the experimental arm. In the control arm, 77% of patients had partial remission. In the experimental arm, it was 66%.

Long-term follow-up found that in the experimental arm, the median PFS was 3.3 years with a. median OS of 7.5 years for all patients. For patients in the experimental arm who received induction therapy without rituximab, the median PFS was 3.1 years and the median OS was 6.7 years. For patients who received rituximab-containing induction therapy, the median PFS was 3.4 years and the median OS was 9.6 years.

For the control arm, the median PFS for all patients was 1.5 years and the median OS was 4.8 years. For patients who received CHOP as an induction therapy, the median PFS was 1.2 years and the median OS was 4.3 years. For patients who received R-CHOP, the median PFS was 1.7 years and the median OS was 5.5 years.

“Whether an autologous HSCT should be generally recommended despite the available additional therapeutic options cannot be appropriately addressed with this trial alone. However, the absence of any significant benefit of autologous HSCT for patients after rituximab-containing induction underlines the need to further explore the value of autologous HSCT in comparison with the most effective regimens available,” study authors write.

According to investigators, patients who received CHOP in the experimental group had much better long-term outcomes compared to those in the control group, highlighting rituximab’s benefit. Additionally, investigators claim that the results of the analysis underline the value of autologous-HSCT regimens in the first-line setting for younger MCL patients.

“However, since the completion of these trials, targeted small molecules such as Bruton’styrosine kinase inhibitors, have become the preferred therapeutic approaches in relapsed mantle cell lymphoma and are nowadays tested in first-line trial,” study authors wrote. “Thus, results from the current generation of studies such as the European Mantle Cell LymphomaNetwork’s TRIANGLE trial (NCT02858258) might further challenge the role of autologous HSCT in young patients with mantle cell lymphoma.”

_REFERENCE:

_{Zoellner A, Unterhalt M, Stilgenbauer S, et al. Long-term survival of patients with mantle cell lymphoma after autologous haematopoieticstem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol 2021;8(9): e648–57. doi:https://doi.org/10.1016/S2352-3026(21)00195-2}