From the Research
The poorest rearrangement in CD19, CD20, CD22, and CD79a expressing lymphomas is typically MYC rearrangement, especially when combined with BCL2 and/or BCL6 rearrangements (known as "double-hit" or "triple-hit" lymphomas). These rearrangements are most commonly found in aggressive B-cell lymphomas, particularly diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma. Patients with MYC rearrangements generally have inferior outcomes with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) therapy, with higher relapse rates and shorter overall survival, as reported in a study published in 2020 1. More intensive regimens like R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) or consideration for consolidative autologous stem cell transplantation may be warranted in these cases. The poor prognosis associated with these rearrangements is due to the dysregulation of cell proliferation (MYC) combined with inhibition of apoptosis (BCL2), creating a particularly aggressive lymphoma phenotype that is resistant to conventional chemotherapy.
Some key points to consider in the management of these patients include:
- Early identification of these rearrangements through FISH testing is crucial for appropriate risk stratification and treatment planning.
- CD19-directed CAR T-cell therapy has shown promise in treating relapsed/refractory B-cell non-Hodgkin lymphoma, but may be limited by antigen escape-mediated relapse, as seen in a study published in 2021 2.
- Sequential antigen loss and branching evolution in lymphoma after CD19- and CD20-targeted T-cell-redirecting therapy can occur, highlighting the complex evolutionary pathways underlying disease progression from these novel therapies, as reported in a study published in 2024 3.
- A recent case report published in 2023 4 highlighted the challenges of diagnosing and managing pediatric high-grade B-cell lymphoma with loss of B-cell markers and CD45, emphasizing the importance of careful diagnostic workup and consideration of novel therapeutic approaches.
Overall, the management of patients with MYC rearrangements in CD19, CD20, CD22, and CD79a expressing lymphomas requires a multidisciplinary approach, incorporating the latest advances in diagnostic testing, targeted therapies, and stem cell transplantation.