Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is an accepted treatment option for patients with relapsed and refractory B-cell lymphomas or high-risk chronic lymphocytic leukemia (CLL). This treatment option is currently being reshaped by the introduction of pathway inhibitors such as ibrutinib, idelalisib, and venetoclax. However, the mid- and long-term efficacy and toxicity of these drugs are not yet fully defined, and most patients need to discontinue their treatment over time because of disease progression or intolerance. Allo-HSCT could induce long-term disease control with curative potential, especially in poor prognosis patients. In the case of relapse after transplantation, the prognosis is dismal. In this context, pathway inhibitors could be promising in the context of lowering the bulky leukemic cells before proceeding to allo-HSCT as well as when used after transplantation to treat or prevent disease relapse. Michallete and colleagues presented the results of a study designed to provide information on the safety and efficacy of ibrutinib when administered after allo-HSCT for mantle-cell lymphoma (MCL) or CLL.
Patients included in this study were those who had been registered with the European Society for Blood and Marrow Transplantation (EBMT) for an allo-HSCT for CLL or MCL and who received ibrutinib for disease recurrence or persistence at any time after transplant. A total of 30 patients who had undergone allo-HSCT were included in this study. Diagnosis was CLL in 27 (90%) patients and MCL in 3 patients, with a median number of treatment lines prior to transplantation of 3. Before transplantation, in CLL patients, del17p was present in 10/27 (37%) patients and del11q was present in 4/27 (15%) patients. Prior to allo-HSCT, 4 patients (2 CLL and 2 MCL) had received an auto-HSCT and 4 other CLL patients had been exposed to ibrutinib for a median of 261 days. Disease response at allo-HSCT was observed in 20/27 (74%) of the CLL patients, and in 1/3 of the MCL patients. A conditioning regimen consisted of reduced intensity in 20/30 (67%) of the transplants and included in vivo T-cell depletion in the majority of cases (17/20).
Acute graft-versus-host disease (GVHD) grade 2-4 was observed in 5/30 (16.6%) patients (3 grade 2, 2 grade 3), whereas chronic GVHD occurred in 15/29 patients but had resolved in 11/15 patients prior to ibrutinib therapy. Patients received ibrutinib for relapse after allo-HSCT (n = 27, median time from allo-HSCT to progression: 22 months), 1 for stable disease and 2 after positive minimal residual disease. Ibrutinib was generally well-tolerated; major toxicities observed after the start of ibrutinib therapy included secondary cancers in 3 patients and toxic epidermolysis in 1 patient. De novo chronic GVHD occurred in 2 patients.
Overall, 23/30 (77%) patients responded after ibrutinib (33% reached complete response [CR]), 21/27 with CLL (8 CR) and 2/3 with MCL (2 CR). At the last follow-up, 20 (67%) patients were still on ibrutinib after a median exposure of 395 days, 19 of them with ongoing response (8 in CR) and 1 too early for response assessment. Ten patients have discontinued ibrutinib, 4 because of toxicity (2 secondary cancers, 2 skin toxicity), and 6 because of disease progression. In total, 4 deaths (all CLL) were observed and were due to disease progression. The median progression-free survival (PFS) after starting ibrutinib in all 30 patients was 23 months, with 1-year overall survival and PFS probabilities of 92%, and 2-year overall survival probability of 75.5%.
The authors concluded that ibrutinib can be safely administered for CLL/MCL relapse after allo-HSCT, with efficacy that is at least similar to nontransplanted patients with high-risk disease.
Michalette M, et al. ASH 2016. Abstract 4659.