Dose-Escalated Therapy May Be Curative for Multiple B-Cell Malignancies

Dose-escalated therapy involving a single agent produced complete and partial responses in patients with different B-cell malignancies.

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Rituximab, a chimeric monoclonal antibody targeting CD20 antigen on B-cells, is considered a standard of care in the treatment of B-cell malignancies (standard dose: 375 mg/m²), especially in combination with cytotoxic chemotherapy as induction therapy or as a single agent for induction and maintenance therapy. Positive activity has been reported in multiple types of B-cell lymphoma, such as diffuse large cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, lymphocyte predominant Hodgkin lymphoma, and Waldenström macroglobulinemia. Dose-escalation of rituximab as a single agent has shown improved activity in previously treated, poor prognosis chronic lymphocytic leukemia.

Lauren M Jacobs, BS, George Washington University, and colleagues presented 4 cases of patients with B-cell malignancies (chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, and Waldenström macroglobulinemia) who received dose-escalated rituximab as a single agent after declined cytotoxic chemotherapy. All patients received weekly induction doses for 4 weeks, starting at 375-500 mg/m² and then followed by weekly or monthly dose escalation to 1500 mg/m². Researchers presented their findings at the American Federation for Clinical Research (Washington DC; April 18, 2017).

Results of the dose-escalation rituximab treatment showed 3 patients (chronic lymphocytic leukemia, mantle cell lymphoma, and follicular lymphoma) achieved complete responses and 1 patient (Waldenström macroglobulinemia) achieved stable disease/partial response. After treatment conclusion, all patients maintained their response for 6.5 to longer than 15 years.

Minimal toxicities were reported as a result of rituximab treatment. Only initial infusion reactions similar to those observed with standard dose infusions were reported. Additionally, there were no serious treatment-related adverse events or infections observed in the patient population.

Researchers concluded that dose-escalated rituximab as a single agent may possibly be curative for some patients with B-cell malignancies. Further studies are required to validate these findings. – Zachary Bessette