A Bortezomib-Based Protocol Induces a High Rate of Complete Remission with Minor Toxicity in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia

Abstract

The treatment of relapsed/refractory acute lymphoblastic leukemia (RR-ALL) presents a true clinical challenge. In 2012, a protocol combining bortezomib, dexamethasone, asparaginase, doxorubicin, and vincristine administered to children with RR-ALL was published with encouraging results. Over the past 5 years, we have implemented this protocol in the adult RR-ALL population (> 18 years) and addressed its feasibility in terms of remission rate and toxicity. Here, we present the results of our experience in 9 patients, all of whom received multiple previous chemotherapy protocols, two of them relapsing after an allogeneic bone marrow transplantation. All of the five B-ALL patients, and two of the four T-ALL achieved complete remission. Of the seven patients achieving complete remission, two patients were referred for allogeneic bone marrow transplantation, two patients were subsequently given blinatumomab, and one patient subsequently received donor lymphocyte infusion followed by blinatumomab. Thus, five out of nine patients treated (55%) were able to proceed to best available therapy in a complete remission. We observed minimal adverse effects, mainly hematological toxicity. We conclude that the bortezomib-based protocol should be evaluated as an effective and well-tolerated treatment option for adult patients either unfit for or failing standard salvage chemotherapy, as a bridge to immunotherapy or allogeneic bone marrow transplantation.

Combination of Donor Lymphocyte Infusion and Blinatumomab for B-Cell Lymphoblastic Lymphoma Relapse after Allogeneic Stem-Cell Transplantation

“…However, in a previous study [11], blinatumomab and DLI were used in combination with chemotherapy, which made it difficult to assess the efficacy of blinatumomab and DLI. Since the other studies have not described whether blinatumomab was used before transplantation [7‒10], it is not possible to compare the effect of blinatumomab before and after transplantation. However, in the present case, blinatumomab had no effect before transplantation but did after transplantation, suggesting that allogeneic T-lymphocytes engaged by blinatumomab suppressed the tumors to which the patient‘s original T-lymphocytes did not respond.…”

“…In the present case, the combination therapy of blinatumomab and DLI allowed us to successfully bridge to the second transplantation. A few previous reports have documented the potential efficacy of this combination therapy in patients with posttransplantation relapse (Table 1) [7‒11]. However, in a previous study [11], blinatumomab and DLI were used in combination with chemotherapy, which made it difficult to assess the efficacy of blinatumomab and DLI.…”

“…In the post-allo-SCT setting, recent reports have also shown the potential benefits of blinatumomab in directing allogeneic CD3+ T-cells to residual or relapsed CD19+ leukemia cells and enhancing the graft-versus-leukemia/lymphoma effect without exacerbating graft-versus-host disease (GVHD) [5, 6]. A few case reports also describe the concurrent use of DLI and blinatumomab and the promising results [7‒11]. Here, we present a case of B-cell lymphoblastic lymphoma (B-LBL) where blinatumomab was ineffective before allo-SCT, but a combination of DLI and blinatumomab was effective in the posttransplantation recurrence period.…”

Opciones para el tratamiento de la recaída en leucemia linfoblástica aguda. Revisión de tema

“…La primera evidencia de su actividad se identificó en un paciente pediátrico de 8 años con recaídas múltiples; se le adicionó bortezomib con dexametasona (Bortezomib 1,2 mg/m 2 días 1, 4, 8, 11) mostrando respuesta 53 . Posterior a esto, diferentes grupos alrededor del mundo han combinado el uso de Bortezomib (1,3 mg/m 2 dos veces por semana) con el esquema de tratamiento estándar para el tratamiento principalmente de leucemias en recaída o refractarias al tratamiento 54,55 , por ejemplo, en México, Nachmias y colaboradores evaluaron el perfil de toxicidad de Bortezomib reportando la ausencia de eventos adversos serios e inclusive sin modificaciones en la frecuencia de neuropatía 56 .…”

The Role of Proteasome Inhibitors in Treating Acute Lymphoblastic Leukaemia

“…Nachmias et al. showed 78% overall response rate in adult patients with relapse/refractory ALL with minimal toxicities when treated with combined chemotherapy and bortezomib ( 67 ). Jain et al.…”