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Case Reports
Figure 1. Blood counts and spleen size changes over time. Shown are the trends of white blood cell count, hemoglobin, platelet count, and spleen size across the clinical course of the patient. The red arrows at the top indicate significant events that occurred during this time.
In addition to eliminating his symptoms, normalizing the spleen size, lymphocytosis, and anemia, the response to pembrolizumab was both rapid and durable. This striking response was associated with the disappearance of the TP53 I195S mutation and raises parallels to the concept of minimal residual disease and its implications in hematologic diseases. While we cannot rule out that sequencing of a bone marrow sample may have identi- fied the mutation, the SMZL cells clearly were circulating (as evidenced by the lymphocytosis and sequencing data in the pre-treatment sample), and there is evidence to suggest high correlation between clonal mutations iden- tified in the bone marrow and bloodstream.11 The persist- ent thrombocytopenia after treatment was of uncertain etio-logy but presumed to be immune-mediated in nature due to the pembrolizumab therapy.
Finally, to gain insight into the mechanism of activity against the SMZL, we stained the bone marrow biopsy specimen for BSAP to highlight the B-cell population and PD-L1. Consistent with the striking response to pem- brolizumab, the abnormal B-cell population uniformly expressed PD-L1 (Figure 2C). In contrast, the surrounding
myeloid and erythroid cells did not appear to be PD-L1 positive and there was no obvious local inflammatory infiltrate.
There are limited data on the use of checkpoint inhibitors for the treatment of MZL, and we are not aware of any study reporting the use of these agents either as frontline therapy or specifically in SMZL. One patient with MZL was treated in a phase Ib study of nivolumab for relapsed or refractory hematologic malig- nancies but the results for this individual were grouped with other lymphoma subtypes and are therefore unavailable.12 There is an ongoing trial of pembrolizumab alone or with idelalisib or ibrutinib for relapsed or refrac- tory lymphomas that allows for MZL, but the full results have not been reported.13 Furthermore, patients enrolled in clinical trials have generally already received numerous therapies and are thus likely more immune suppressed, in contrast to this case where the patient was therapy- naive. While our data suggest that frontline PD-1 blo- ckade may be efficacious for the treatment of SMZL, we recognize that established frontline therapy options in this disease, in particular rituximab, are already effective
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haematologica | 2021; 106(2)