Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties

Abstract

The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.

Allogeneic transplantation in high-risk chronic lymphocytic leukemia: a single-center, intent-to-treat analysis

“…The reason for this could just be chance because of the small sample size, but it is in line with a recent EBMT analysis demonstrating 12month non-relapse mortality rates of 5% and 10% in ibrutinib-pretreated patients with mantle cell lymphoma and CLL, respectively. 8 In contrast to the findings of the EBMT study, the post-transplant relapse risk was also quite low in our series with only four events, three of which occurred in patients with refractory disease prior to transplantation. It remains to be shown whether our transplant strategy (bridging with pathway inhibitor therapy until maximum response, intensive conditioning with 8 Gy total body irradiation plus fludarabine in 11 patients, treosulfan 30 g plus fludarabine in 5 patients; pathway inhibitor discontinuation at day -1) contributed to this, or whether other factors played a role.…”

Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019

“…has not yet significantly affected the natural course of the disease and thus transplant indications. On the other hand, ibrutinib might be beneficial for bridging patients with MCL to allogeneic HSCT [84]. Studies testing ibrutinib as part of first-line therapy are ongoing.…”

Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial

“…However, late relapses do occur, and these patients may benefit from strategies involving innovative pathway inhibitors. Taking into account preliminary data suggesting that allo-HCT can be safe and effective in ibrutinib-sensitive but chemoimmunotherapy-refractory patients with HR-CLL, 13 the information on long-term results of transplantation provided here may help when counseling patients with advanced CLL about potential treatment options. Years from HCT Percent relapsed Figure 2.…”