ANIMALS 40 client-owned dogs with a histopathologically confirmed diagnosis of peripheral nodal lymphoma and an expected survival time of > 4 weeks with treatment.
PROCEDURES Treatment consisted of a combination of L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone (L-CHOP) or an identical protocol except for the omission of prednisone (L-CHO). The primary outcome of interest was progression-free survival time. Veterinary caregivers and assessors of outcome were not blinded to treatment assignment. Treatment assignment was concealed from the owners of study dogs prior to enrollment, but was revealed after written informed consent was provided.
RESULTS The trial was terminated early because of slow enrollment. The 40 dogs successfully enrolled in the study were randomly assigned to the L-CHOP (n = 18) or L-CHO (22) group; results for all 40 dogs were analyzed with respect to the primary outcome. Median progression-free survival time was 142.5 days for dogs receiving L-CHO and 292 days for dogs receiving L-CHOP (hazard ratio, 1.79; 95% confidence interval, 0.85 to 3.75). Serious adverse events were more common among dogs receiving L-CHO. However, this difference was not significant.
CONCLUSIONS AND CLINICAL RELEVANCE The exclusion of prednisone from the L-CHOP protocol did not appear to result in improved progression-free survival time for dogs with peripheral nodal lymphomas. However, the present trial was likely underpowered to detect a clinically meaningful difference in progression-free survival time between groups.
OBJECTIVE To measure programmed cell death ligand-1 (PD-L1) mRNA expression in archived primary nodal diffuse large B-cell lymphoma (DLBCL) specimens of dogs and determine whether that expression was associated with progression-free survival time (PFST).
SAMPLE Archived tumoral lymph node specimens from 42 dogs with DLBCL and lymph node specimens from 10 healthy dogs (controls).
PROCEDURES Archived tumoral and control lymph node specimens underwent multiplex qPCR analysis with probes and primers against canine PD-L1 and glyceraldehyde 3-phosphate dehydrogenase (housekeeping gene) to determine PD-L1 mRNA expression. The 2−ΔΔCt method was used to calculate the fold change in PD-L1 expression in DLBCL specimens relative to that in control lymph nodes. Kaplan-Meier and Cox proportional hazard analyses were used to evaluate the association of various tumoral and clinical factors with PFST.
RESULTS The fold change in PD-L1 mRNA expression in DLBCL specimens relative to control specimens ranged from 0.21 to 7.44. Twenty-one of 42 (50%) DLBCL specimens had a PD-L1-fold change > 1, which suggested PD-L1 was overexpressed in those specimens. Median PFST was 249 days for dogs with DLBCL. The PFST was not associated with PD-L1 mRNA expression but was associated with thrombocytopenia at the time of diagnosis (hazard ratio, 2.56; 95% confidence interval, 1.28 to 5.15).
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that tumoral PD-L1 mRNA expression varied among dogs with DLBCL and that PD-L1 MRNA was overexpressed in half the study population. Therefore, anti–PD-L1 therapies may be clinically beneficial for some dogs with DLBCL.
Objective—To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs.
Sample—10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma.
Procedures—Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis.
Results—FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild.
Conclusions and Clinical Relevance—This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.