Venetoclax in upfront induction therapy for primary plasma cell leukemia with t(11;14) or BCL2 expression

This is the authors' abstract. We don't add key points for this paper.

Primary plasma cell leukemia (pPCL) is a rare, but aggressive form of plasma cell dyscrasia. It is defined by greater than 20% plasma cells or an absolute plasma cell count greater than 2 10/L circulating in peripheral blood. Overall survival, though modestly improved with newer therapies, is approximately 12months. Given the poor prognosis, novel regimens are necessary to improve outcomes [1,2]. We present two cases to demonstrate the use of venetoclax in upfront induction therapy in pPCL with t(11;14) or BCL2 overexpression. In the first case, a 64 year-old male presented with epistaxis, uncontrolled hypertension, and anorexia was found to have anemia, thrombocytopenia, hypercalcemia and acute kidney injury (hemoglobin 7.5 g/dL, platelets 118 10/uL, calcium 12.9 g/dL, creatinine 15mg/dL). Skeletal imaging revealed lytic lesions in the skull and thoracic spine. Further evaluation revealed serum protein electrophoresis M protein 0.5 g/dL, serum immunofixation kappa light chain, serum kappa free light chain (FLC) at 65,300mg/L, b2 microglobulin 72.1mg/dL and 20% plasma cells on peripheral flow cytometry. A bone marrow showed extensive (90%) involvement of PCL with cyclin D1-positivity, kappa light chain restriction, and Ki67 proliferation index 10%. FISH revealed t(11;14). He was initiated on hemodialysis and remains on dialysis post hospitalization. He received induction therapy with VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide). Cyclophosphamide was stopped due to development of hemorrhagic cystitis. Repeat paraprotein parameters showed less than a partial response with kappa FLC 37,663mg/L, M protein 0.3 g/ dL, and 2% circulating plasma cells. Therefore, therapy was switched to KPD-PAVE: carfilzomib 20mg/m D1 and 70mg/m D2 and D8; pomalidomide 4mg D1-5, dexamethasone 40mg D1-5; cisplatin 12.5mg/m D1-4, adriamycin 10mg/m D1-4, etoposide 75mg/m CI D1-4, and venetoclax 400mg D1-14. Repeat evaluation four weeks after treatment showed partial remission with kappa FLC at 630mg/dL and no circulating plasma cells. Planned autologous transplant was delayed due to insurance coordination. In the interim, he was treated with KPVd: carfilzomib 70mg/m D1, 8, 15; pomalidomide 4mg D1-21; venetoclax 400mg D1-15; dexamethasone 40mg D1, 8, 15 and 22. However, he received a partial cycle due to hospitalization for atrial fibrillation requiring cardioversion. His kappa FLC levels continued to decrease to 106mg/dL. Three months after the partial cycle of KPVd, he underwent high dose G-CSF for stem cell mobilization. Subsequently, he received tandem autologous transplants with melphalan 140mg/m. Post first transplant, a repeat bone marrow biopsy revealed persistent minimal residual disease (MRD) and therefore, he proceeded to a tandem transplant 7 months after the initial transplant. He tolerated both transplants without complications. Repeat bone marrow biopsy 6 months after transplant showed persistent MRD and he was initiated on venetoclax maintenance treatment, initially at 100mg daily and increased to 200mg daily. However, he was unable to receive the planned goal dose of 400mg due to persistent transfusion independent thrombocytopenia. Four months after venetoclax initiation, FLC increased confirming progression of disease. Venetoclax was discontinued and daratumumab, carfilzomib, and dexamethasone were initiated. Presently, he is in a second remission. In the second case, 40 year-old female presented to the hospital with 2 months of excessive vaginal bleeding, weight loss, and night sweats. Lab abnormalities revealed a hemoglobin 2.1 g/dL, white blood cell count 66.9 10/ mL, platelet count 115 10/mL, creatinine 1.93mg/dL. Further diagnostics revealed an IgG level 13,203mg/dL, M protein level 9.1 g/dL, lambda FLC 5,154mg/L. Peripheral flow cytometry revealed 70–80% plasma cells. Bone marrow biopsy confirmed extensive (80%) involvement of plasma cells with IgG lambda restriction. Immunohistochemistry (IHC) analysis was positive for