P440 Allogeneic Stem Cell Transplantation can be Successfully Delivered Following BTKI Therapy Failure Following R-bac Re-induction Chemotherapy in Patients with Mantle Cell Lymphoma

Background: Allogeneic haematopoietic stem cell transplant (alloHSCT) is a potentially curative treatment option for patients with mantle cell lymphoma (MCL). Bruton’s Tyrosine Kinase inhibitors (BTKi) eg ibrutinib are highly effective in relapsed/refractory (R/R) MCL. The optimal timing of alloHSCT in this setting is not currently known. Here we report data on two groups of patients undergoing alloHSCT for R/R MCL following BTKi therapy. The first received BTKi as a bridge to alloHSCT, and a second underwent alloHSCT following BTKi failure and subsequent treatment with rituximab, bendamustine and cytarabine (R-BAC) chemotherapy Methods: Twenty eligible patients were retrospectively collected across 13 centres (2016-2019). Follow-up was censored in 07/2019. Eleven patients received alloHSCT following ibrutinib as second-line treatment, 9 received alloHSCT after BTKi failure and subsequent salvage chemotherapy with R-BAC. Progression-free survival (PFS) and overall survival (OS) analyses were performed using Kaplan Meier methods and Cox regression with comparisons between categories using the log-rank test. Results: Median OS of the whole group post alloHSCT was not reached (63% at 1 year). Median follow up post alloHSCT was 12 months. AlloHSCT post BTKi alone Of patients transplanted following BTKi as bridging therapy, all received ibrutinib as second-line treatment (7/11 prior NORDIC protocol, 4/11 high dose cytarabine (HDAC)). Nine had undergone prior autologous stem cell transplantation. 1/11 was primary refractory to HDAC. Median time on treatment with ibrutinib was 6 (3-20) months. 5/11 achieved a complete response / complete response undetermined (CR/Cru) to ibrutinib, 5/11 had a partial response (PR) and one was transplanted after progressive disease (PD). 2/11 patients were transplanted from a sibling donor, 7/11 from an unrelated donor and 2/11 from a haploidentical donor. Conditioning regimen was fludarabine/melphalan in 8/11 patients. 1/11 received BEAM conditioning and 2/11 received fludarabine/cyclophosphamide/TBI. T-cell depletion with alemtuzumab was used in 8/11 patients. Median OS of patients was not reached (OS at 1 year 52%). All 4 deaths were due to transplant-related mortality (3/4 deaths were GvHD related). AlloHSCT post BTKi and subsequent R-BAC Of patients transplanted following BTKi failure and subsequent R-BAC treatment. 8/9 had received prior ibrutinib, 1/9 had received M7583 (Merck BTKi). All patients had previously stopped BTKi due to PD/lack of response. 5/9 patients achieved a CR with R-BAC prior to alloHSCT, 1/9 PR and 2/9 had stable disease, best response was unknown in 1/9. Eight are alive with a median follow up of 4.3 months (median OS not reached, estimated 1 year OS 85.7%). 1/9 patient died due to PD. There was no significant difference in OS between patients receiving alloHSCT following BTKi bridging, compared with patients undergoing alloHSCT following BTKi failure and subsequent R-BAC (p = 0.39, log-rank test). Conclusions: We have recently reported that R-BAC is a highly efficacious regimen in the post BTKi setting. These data demonstrate that alloHSCT following BTKi failure and subsequent R-BAC salvage treatment represents a reasonable treatment option for a subset of patients. Thus, maximising the PFS on BTKi and reserving alloHSCT post BTKi failure and subsequent salvage with R-BAC may be a reasonable strategy for selected patients.

Citation

Lewis, D., McCulloch, R., Eyre, T., Tucker, D., Shah, N., Turner, D., Miles, O., Crosbie, N., & Rule, S. (2020). Allogeneic stem cell transplantation can be successfully delivered following BTKI therapy failure following R-BAC re-induction chemotherapy in patients with mantle cell lymphoma. Bone Marrow Transplantation, 55, 2347–2349. https://doi.org/10.1038/s41409-020-01120-w

DOI

10.1038/s41409-020-01120-w

URI

https://hdl.handle.net/20.500.14709/1033