This month, Jorge Castillo, MD, discusses treatment of low-grade B-cell lymphoma with high-risk cytogenetics.
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An 82-year-old asymptomatic patient presented with an elevated white blood cell count of 24×109 cells/L, a hemoglobin level of 11 g/dL, a platelet count of 56×109/L, and an absolute lymphocyte count of 20×109 cells/L. The marrow was hypercellular (80%-90%) with small lymphocytes representing 70%-80% of the marrow cellularity. By flow cytometry, the lymphocytes were CD20-expressing and kappa light chain–restricted B cells, and were negative for CD10, CD200, and BCL1. A subset showed dim CD5 expression, but CD5 was largely negative and the cells were also negative for CD19, CD23, FMC7, CD11c, and CD38. Cytogenetics showed deletion 7q, an unbalanced translocation between 3q and 21p resulting in gain of 3q; monosomy 17/deletion of TP53, and other aberrations in 17/20 cells. MYD88 was wild type. The pathologists characterized this a low-grade B-cell lymphoma, either marginal zone or something else. My concern is about the TP53 loss and use of single-agent rituximab with likely shorter time to progression and survival. I am favoring instead using ibrutinib upfront given poor cytogenetics and would appreciate your thoughts.
Based on the data reported above, I agree with your assessment that the patient’s disease is probably an MYD88 negative lymphoplasmacytic lymphoma (LPL) or a marginal zone lymphoma (MZL). Single agent ibrutinib 420 mg by mouth once daily would be a reasonable option, as ibrutinib is approved for both conditions. Furthermore, the presence of deletion 17p increases the likelihood that the patient’s disease would have a degree of chemoresistance. The rate of response to ibrutinib does differ between these conditions, with 90% response rates in LPL and 50% in MZL. In case this is truly an MYD88 negative LPL, I would consider adding rituximab to ibrutinib per the INNOVATE study.1 Rituximab is administered at an intravenous dose of 375 mg/m2 once weekly on weeks one to four and 17 to 20. Ibrutinib therapy would be indefinite until disease progression or unacceptable toxicity.
- Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenström’s macroglobulinemia. N Engl J Med. 2018; 378:2399-2410.
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NEXT MONTH'S CLINICAL DILEMMA
I am treating a 40-year-old female patient with a new diagnosis of aggressive systemic mastocytosis. She had a years-long history of progressive back pain, further exacerbated by a motor vehicle accident in January 2020.
A CT scan of her chest, abdomen, and pelvis showed subcentimeter left axilla nodes and dense, diffuse, bony sclerosis with small areas of lysis. Her bone scan revealed diffuse increased bony remodeling in the distribution of the adult red marrow; metastatic or metabolic bony disease was felt to be unlikely based on lack of heterogeneity and peripheral involvement. Her complete blood cell, metabolic, and liver profile were within normal limits.
The patient had no complaints aside from back pain and no unusual allergic reactions or sensitivities. She has a reported history of blotchy erythema to the thighs when exposed to the cold (a dermatologist diagnosed telangiectasia macularis eruptiva perstans [TMEP] on skin biopsy years ago). She has no family history of blood disorders. She was not taking any medications and has no known drug allergies. She reports that she does not smoke and occasionally consumes alcohol. The exam revealed no rashes and no organomegaly.
Subsequent bone marrow analysis was normocellular for her age, revealing many aggregates/clusters of CD117+ mast cells and areas of densely packed spindle-shaped mast cells that account for 30%-40% of the marrow. There was minimal surrounding fibrosis. Karyotype was normal, molecular testing was positive for KIT D816V although at low variant allele frequency. Her tryptase level was 73.7 ng/mL.
The patient meets the major and three minor criteria for aggressive systemic mastocytosis, with one B finding (bone marrow mast cells >30%) and one C finding (lytic lesions). She is starting on midostaurin 100 mg orally twice daily.
Given her young age, would you consider allogeneic hematopoietic cell transplantation? If so, what timing would you recommend? Is there a particular bisphosphonate you would recommend? We have access to zoledronic acid and pamidronic acid in our medical day unit. Would you suggest cromolyn sodium for her bone pain?
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