Ruxolitinib, Venetoclax Combo Delays Disease Progression in Case Report of BCR-JAK2 Rearranged Myeloid Neoplasm

Researchers detailed the case of a patient with therapy-related BCR-JAK2⁺ myeloid neoplasm with significant disease in his lymph nodes, suggesting that a combination of a JAK2 inhibitor and a BCL2 inhibitor may help prolong disease progression.

While allogeneic stem cell transplantation (allo-SCT) is the only approach that demonstrates an ability to elicit long-term remission in these patients, JAK2 inhibitors like ruxolitinib have shown some benefit in controlling disease.

In the current case report, a 54-year-old patient received a combination of ruxolitinib with venetoclax after his disease progressed on ruxolitinib monotherapy. The treatment combination delayed disease progression for a year and a half, suggesting the combination may be a viable option for patients not eligible for allo-SCT.

“Combining these 2 inhibitors may be strategic since downstream transcriptional targets of JAK/ STAT signaling include antiapoptotic members of the BCL2 family, such as BCL2 and BCL-xl,” explained the researchers. “Several preclinical studies have suggested a beneficial synergistic effect of combining these 2 inhibitors in patients with JAK2-mutated hematological malignancies.”

The description of hematologic malignancies with a BCR-JAK2 rearrangement has historically been scarce in literature according to researchers, who highlighted the importance of better understanding the phenotype of the rare disorders, particularly as JAK2-rearranged malignancies have now been included in major classification systems.

For example, in 2017, the World Health Organization revised their Classification of Myeloid Neoplasms and Acute Leukemia to include myeloid neoplasm with PCM1-JAK2 rearrangement as a new provisional entity.

“While the patient described here does not have a hematological malignancy with a PCM1- JAK2 rearrangement, many experts in the field advocate to classify those rare cases with a JAK2 rearrangement, including gene partners other than PCM1, in the same category because of similar clinical features,” researchers said.

“This is also highlighted by the inclusion of patients with a BCR-JAK2 rearrangement in the latest version of the US National Comprehensive Cancer Network guidelines for ‘Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Fusion Genes’ (version 3.2021),” they continued.

In the current case report, the patient received ruxolitinib 20 mg twice daily for his disease, showing early improvement in blood counts with a reduced need for transfusions.

However, after 5 months the patient experienced worsened anemia, thrombocytopenia, and leukocytosis, and his spleen remained enlarged. As a result, venetoclax was added to his treatment regimen. When evaluated for allo-HCT, the patient was deemed ineligible due to weakened pulmonary function.

While on the treatment combination, the patient’s blood counts normalized, his spleen dropped from 19 cm to 13.1 cm, and scans showed stable disease. Notably, the combination yielded minimal toxicity concerns for the patient.

Reference:

Lap CJ, Nassereddine S, Liu M, Nava VE, and Aggarwal A. Combined ruxolitinib and venetoclax treatment in a patient with a BCR-JAK2 rearranged myeloid neoplasm. Case Rep Hematol. Published online July 28, 2021. doi:10.1155/2021/2348977