Despite Benefits of Stem Cell Transplant in MCL, Best Practices Remain Elusive

Both autologous stem cell transplant (autoSCT) and allogeneic stem cell transplant (alloSCT) can be used as consolidation therapy in patients with mantle cell lymphoma (MCL), according to results from a single-center analysis, presented in a poster at the 2020 Transplantation & Cellular Therapy Meetings. However, the benefit of alloSCT is offset by an increased risk of transplant-related mortality and the development of graft-versus-host-disease (GVHD).

MCL is an aggressive form of lymphoma with the presence of translocation (11:14) or the cyclin D1 mutation. Patients generally tend to have poor survival with chemotherapy alone, and both autoSCT and alloSCT have improved outcomes in this patient population in previous clinical trials. However, appropriate strategies for transplant have not been defined in this space.

In a single-center study, 56 patients with MCL received transplant as consolidation therapy for MCL, and 53 patients were analyzed with a median follow-up of 13.6 years (range, 80-5000 days). In terms of transplant, 21 patients received autologous, 20 had nonmyeloablative allogeneic, 10 had myeloablative, and 2 had reduced intensity conditioning.

The median age of patients at the time of transplant was 57 years. For 32 allografts, donor types included haploidentical donors (n = 1), MSD, (n = 16), and MUD (n = 15), while 21 patients received autografts.

In the autoSCT arm, the median age was 59.7 years (range, 37.7-69.8), and 14 out of 21 patients were male and 7 were female. Ten patients were determined at low-disease risk and 11 high. Overall, 16 patients achieved a complete response (CR), while 2 patients reached a partial response (PR), and 3 were determined primary induction failure/relapse. The graft source in all patients was peripheral blood.

The median age in the alloSCT arm was 56.1 (range, 34-67.8), and all 32 patients were male. One patient had low-risk disease, 3 had intermediate risk, and 28 were high-risk. Overall, 8 patients in this arm achieved a CR, 4 a PR, and 20 had primary induction failure/relapse. Thirty-one patients had peripheral blood as a graft source compared with 2 bone marrow.

In the alloSCT arm, the conditioning regimens were non-myeloablative (n = 20), reduced-intensity conditioning (n = 2), and myeloablative (n = 10). Additionally, 15 patients had matched unrelated donors as their donor source.

A few select subgroups of patients were significant for overall survival (OS), including race (P= 0.009), transplant type (P= 0.00293), and donor type (P= 0.0143). The patient’s gender also had a trend for better OS (P= 0.07). For autoSCT, the 1-year OS was 74.3%, while the 5-year OS was 53.4%.

In Hispanic/Black/Native Hawaiian patients, the 1-year OS was 0.333 (95% CI, 0.009-0.774) versus 0.769 (95% CI, 0.620-0.865) in Caucasian patients. In males versus females, the 1-year OS was 0.707 (95% CI, 0.548-0.819) and 1.000 (95% CI, NA-NA), respectively.

In the alloSCT arm, the 1-year OS in the nonmyeloablative allogeneic group was 0.744 (95% CI, 0.489-0.885) versus 0.417 (95% CI, 0.152-0.665). One-year progression-free survival (PFS) was 78.4%, and 5-year PFS was 65.1% in the allogeneic arm. The only significant factor for PFS was disease status at the time of transplant (P= 0.0185).

Six patients developed acute GVHD (26%), whereas 5 patients developed chronic GVHD, limited in 3 patients (9%) and extensive in 5 patients (22%). The primary cause of death in this analysis was treatment-related in 8 patients, including 4 deaths due to GVHD, 3 to pulmonary, and 1 to multiple organ failure; disease progression in 8 patients; unknown in 4 patients; and other in 1 patient.

Study authors concluded that more randomized clinical trials or larger retrospective studies may be useful in determining the best transplant strategy for patients with MCL in the consolidation setting.

“In the era of better therapies for MCL, CR at the time of transplant may be the most important factor for long term outcome of [patients with MCL],” the study authors wrote.

Reference:

Naik S, Minagawa K, Zheng H, et al. Patterns of Transplant and Survival Outcomes for Mantle Cell lymphoma over Last 17 Years: Single Center Experience. Poster presented at: The Transplantation & Cellular Therapy Meetings; February 19-23, 2020; Orlando, FL.