A case study published in Leukemia and Lymphoma described a patient with a diagnosis of Waldenström Macroglobulinemia (WM) that had subsequently undergone histological transformation to refractory high grade B-cell lymphoma and was successfully treated with CD19-targeted chimeric antigen receptor (CAR)-T cell therapy.1

WM is a type of B-cell non-Hodgkin lymphoma (NHL), typically characterized by overproduction of monoclonal immunoglobulin M, as well as infiltration of malignant lymphoplasmacytic cells into the bone marrow.

Although considered incurable, WM often follows an indolent course and some patients can be asymptomatic for long periods. Rarely, the disease transforms into a more aggressive form of NHL that has been associated with a poor prognosis.

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The patient described in the case study was a 71-year-old man who was first diagnosed with WM in 1998. The patient was monitored without undergoing active treatment for a period of 12 years, at which time he developed anemia and splenomegaly. At that time, he underwent treatment with 6 cycles of fludarabine and rituximab and achieved a partial response to treatment. Following a worsening of symptoms 4 years later, the patient was treated with 6 cycles of bendamustine and rituximab.

Biopsy of an enlarged cervical lymph node performed at that time revealed high-grade B-cell lymphoma that was “clonally related to the previously seen lymphoplasmacytic infiltrate, consistent with transformation.”

The patient subsequently achieved a complete response to 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) plus ibrutinib followed by 6 months of ibrutinib maintenance therapy that lasted for 18 months.

Salvage therapy included 2 cycles of rituximab, dexamethasone, cytarabine, cisplatin (R-DHAP) followed by 1 cycle of rituximab plus high-dose cytarabine, followed by autologous stem cell transplantation several months later.

As the patient’s disease was considered to be chemorefractory based on subsequent imaging and pathological analyses, he was treated with axicabtagene ciloleucel, a CD19-targeted CAR-T cell therapy currently approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma, including high grade B-cell lymphoma, after 2 or more lines of systemic therapy.2

Although the patient experienced pancytopenia, grade 1 cytokine release syndrome, and grade 1 neurotoxicity following CAR-T therapy, he achieved a complete response 1 month following treatment.

Notably, there was no evidence of either underlying WM or transformed disease at 6 and 12 months follow-up.

The study authors noted that “longer term follow up in this patient will be informative, as late relapses have occurred even in patients who achieve a deep response after transplant. CAR-T cell therapy may be an effective treatment for relapsed or refractory WM that has not yet undergone histological transformation, as CD19 is almost universally expressed on lymphoplasmacytic lymphoma cells.” The researchers concluded that further analysis of this is warranted in the context of clinical trials.


  1. Bansal RJurcic JGSawas AMapara MYReshef R. Chimeric antigen receptor T cells for treatment of transformed Waldenström macroglobulinemia. Leuk Lymphoma.doi:10.1080/10428194.2019.1665668
  2. Axicabtagene ciloleucel (Yescarta) [package insert]. Santa Monica, CA: Kite Pharma, Inc; 2019.