Blinatumomab As Primary Treatment for Adult Newly Diagnosed B-ALL

Background

Although the multi-drug chemotherapy regimen known as VDCLP can induce hematological remission in 70-90% of adults with acute lymphoblastic leukemia, many patients, particularly young women, remain concerned about chemotherapy-related complications such as alopecia, infection, and bleeding risk. Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, has notably enhanced the remission rates for relapsed and refractory adult ALL when combined with chemotherapy. Additionally, the combination of blinatumomab and TKI has demonstrated significant efficacy in treating ph+ adult ALL. However, there is currently no clinical evidence indicating whether blinatumomab, as a first-line therapy, can achieve higher remission rates and reduce toxic and side effects in newly diagnosed adult ALL patients. In this report, we present the findings from our center where we have used the blinatumomab regimen as the primary treatment for adult ALL.

Method

A total of 12 newly diagnosed adult ALL patients were enrolled in this study. These patients consisted of 3 males and 9 females, with ages ranging from 23 to 72 years. All patients underwent bone marrow aspiration and were diagnosed according to morphology, immunophenotyping, cytogenetics, and molecular biology（MICM）. They were categorized into 7 cases of Ph+ ALL and 5 cases of Ph- ALL(Table1). All patients received a combination regimen consisting of vincristine (1.4mg/m2 on D1 and D8), prednisone (1mg/kg orally from D1-14,decrease gradually after D15), and blinatumomab. Blinatumomab was initiated on D3 and administered in an escalating dose manner for 15-28 days (9 μg/day from D1-7, 28 μg/day from D8) .

Result

Seven patients completed the 15-day treatment course, and five patients completed the full 28-day treatment course. Bone marrow morphology and MRD assessments were conducted on days 15 and 28 post-treatment. On day 15, the hematological remission rate (HCR) of bone marrow reached 100% (12 out of 12 patients), while the MRD negativity rate was 16.7% (2 out of 12 patients tested). five patients completed the full 28-day treatment course, and upon re-examination on day 28, maintained a 100% HCR. Among these, the MRD negativity rate improved to 80% (4 out of 5 patients). No significant difference in HCR was observed between ph+ ALL and ph- ALL groups.

Five patients underwent allogeneic stem cell transplantation, and four of these patients were thriving, while one patient died of COVID-19 infection 3 months after transplantation. Of the seven patients without a transplant, two elderly patients received non-chemotherapy maintenance treatment but unfortunately passed away due to disease recurrence within 12 months. Four patients with ph+all received alternating chemotherapy and oral TKI treatment and are currently in good health and alive. One patient with ph-all received CAR-T therapy and still alive with MRD negative. (Figure1)

Discuss

Our center's findings further corroborate that for adults with new diagnosis Ph+/- ALL, initial treatment involving blinatumomab combined with low-dose chemotherapy can attain a 100% HCR rate, absent of pronounced toxicity or side effects, thereby offering a viable option for patients intolerant or averse to chemotherapy. Currently, there is insufficient evidence to determine the ideal duration for blinatumomab treatment in adult ALL patients. However, for refractory and relapsed ALL cases, a continuous 28-day course of blinatumomab therapy may be required. Initial findings from our center indicate that after 15 days of VP+blinatumomab therapy, all patients achieved hematological remission. This outcome is particularly advantageous for patients in developing nations and regions. Switching to chemotherapy or oral TKI promptly after 15 days of blinatumomab treatment can considerably decrease treatment expenses and minimize complications associated with combined chemotherapy. Nevertheless, the sample size in this study is limited, necessitating further clinical evidence to validate this perspective.

Chen:Nuwacell Biotechnologies Co., Ltd.: Current Employment.