Treatment of Relapsed/Refractory t(11;14) Multiple Myeloma and High-Risk Myelodysplastic Syndrome With Venetoclax

Patients with multiple myeloma (MM) have an inherent risk for secondary myeloid malignancies. Innovative approaches to treatment are needed when these hematologic malignancies co-occur. Venetoclax (VEN), a BCL2 inhibitor, has been used in combination with Azacitidine in acute myeloid leukemia, in the trial setting in high-risk myelodysplastic syndrome (MDS), and in t(11; 14) MM in the salvage setting. Here, we present a case report of concurrent treatment of high-risk MDS and t(11; 14) MM in a patient, using VEN-based therapy. Following diagnosis with IgG t(11; 14) MM, the patient received treatment with Lenalidomide, Bortezomib, and Dexamethasone and achieved a very good partial response. She subsequently proceeded to autologous stem cell transplant and thereafter continued on Lenalidomide maintenance. Relapsed disease was noted 3 years following transplant, with a concurrent diagnosis of a high-risk MDS (mutations in NRAS and DNMT3A). Given the known efficacy of VEN in her concomitant malignancies, we elected to use a VEN-based regimen, at a lower dose of VEN than has been shown to be efficacious in t(11; 14) MM. Bone marrow biopsy demonstrated response from the perspective of both malignancies, until she had relapsed disease with a mixed phenotype acute leukemia ∼ 19 months after relapsed MM/diagnosis of high-risk MDS. Overall, this case demonstrates successful treatment of both hematologic malignancies at a lower dose of VEN than previously shown to be efficacious in t(11; 14) MM.