Salvage Therapy in Early Relapse of T-Lymphoblastic Leukemia/Lymphoma Using Daratumumab/Nelarabine Combination: Two Consecutive Cases

Abstract

Treatment of early relapses of T lymphoblastic leukemia/lymphoma is often unsuccessful. We tested an experimental regimen containing daratumumab and nelarabine in two young patients with early relapses of T lymphoblastic lymphoma and T-ALL, respectively. Both patients achieved a deep complete remission. Combining daratumumab with chemotherapy may have a role in relapsing T lymphoblastic leukemia/lymphoma.

Daratumumab and Nelarabine Treatment as Salvage Therapy for T-Lymphoblastic Lymphoma: A Case Report

“…Daratumumab is an option to be considered due to high CD38 expression on the cell membranes of T-lymphoblasts, which seems to persist even post-treatment without leading to downregulation processes and avoiding a loss of response to this drug [ 14 ], although it should be noted that this persistence seems to be lower than the observed in multiple myeloma (MM) cases [ 15 ]. Studies conducted regarding MM suggest that daratumumab’s effectiveness could correlate with the expression of CD38 found in the tumor [ 16 ]. The regimen involving daratumumab and nelarabine seems to offer some advantages as salvage therapy according to some studies, but experience in this area is clearly limited by this regimen’s use in only a few cases or to treat T-ALL [ 16 , 17 ].…”

“…Studies conducted regarding MM suggest that daratumumab’s effectiveness could correlate with the expression of CD38 found in the tumor [ 16 ]. The regimen involving daratumumab and nelarabine seems to offer some advantages as salvage therapy according to some studies, but experience in this area is clearly limited by this regimen’s use in only a few cases or to treat T-ALL [ 16 , 17 ]. Its broad spectrum of activity offers a treatment opportunity in other lymphoid processes beyond MM [ 6 ], showing tumor burden reduction in animal models using daratumumab.…”

The role of daratumumab in relapsed/refractory CD38 positive acute leukemias—case report on three cases with a literature review

“…The real-world data regarding the usage of daratumumab are limited to 34 cases ( Table 3 ). Daratumumab has been used in pediatric and adult patients ( 24 , 27 ). Daratumumab proved to be effective in patients with MRD positivity, especially those with MRD relapse after transplantation.…”

“…Neurological side effects (described as maculopathy with paresis of the upper and lower limbs) were observed in one patient after transplantation with conditioning with TBI. The patient was treated with nelarabine and daratumumab; however, it is unclear which agent was responsible for the observed neurotoxicity ( 24 ). In fact, nelarabine in monotherapy is known to induce grade III–IV neurologic toxicities in approximately 10% of patients ( 2 ).…”