Contributions
Abstract: PB2233
Type: Publication Only
Background
Secondary plasma cell leukemia presenting as a myeloma relapse after multiple prior lines of therapy is a condition with dismal prognosis and a usual survival of only a few weeks. Recently, it has been shown that multiple myeloma with translocation t(11;14) may be exquisitely sensitive to the bcl-2 inhibitor venetoclax.
Aims
Here we report the highly successful therapeutic result of a myeloma patient diagnosed 11 years ago who received 8 prior lines of therapy that included all available therapeutic agents (including thalidomide, lenalidomide, bortezomib, carfilzomib, bendamustine, daratumumab and twice high-dose melphalan with autologous stem cell transplantation). The patient presented at our institution with hypercalcaemia (3.01 mmol/l), cytopenias, ECOG 3 physical condition due to profuse bone pain. Blood smear indicated plasma cell leukemia, flow cytometry analysis confirmed plasma cell leukemia with circulating plasma cells at the level of 14 G/l.
Methods
We are reporting on a clinical case documented with clinical laboratory, FISH and flow cytometry analysis.
Results
Since the patient was known to have broad resistance to available myeloma therapies, however had translocation t(11;14) since diagnosis, after initial zoledronic acid infusion, we elected to administer bortezomib-dexamethason-bendamustine combination with the addition of clarithromycine 500 mg BID and 400 mg daily dose of venetoclax orally. On day 3, the circulatory plasma cells disappeared and grade II tumor lysis syndrome developed (LDH max at 3107 U/l, with manageable hyperuricaemia, hyperkalemia, and hyperphosphatemia). The overall clinical state of the patient was steadily improving, he currently continues to receive venetoclax in monotherapy at the dose level of 400 mg daily. As CYP3A4 inhibition, initially clarithromycine was administered, but after 1 month due to GI symptoms, clarithromycine was switched to fluconazole 100 mg daily that was well tolerated. After 5 month of venetoclax 400 mg OD (only) in this pharmacologically enhanced monotherapy, the patient is ECOG 0, his M-protein is detectable only by immunofixation, free light chains and their ratio are normal, blood counts are in the normal range. Bone marrow aspiration indicated pathological plasma cells below the level of detection of available flow cytometry.
Conclusion
Our case indicates that in secondary plasma cell leukaemia refractory to available prior therapies and exhibiting translocation t(11;14), venetoclax may be a potentially effective salvage therapy. Additionally, pharmacological enhancement of 400 mg daily dose of venetoclax - with CYP3A4 inhibitors clarithromycine or azole antifungal agents - may provide a cost effective alternative to the generally recommended 1200 mg daily dose of this expensive novel medication.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): BCL2, Myeloma, Plasma cells
Abstract: PB2233
Type: Publication Only
Background
Secondary plasma cell leukemia presenting as a myeloma relapse after multiple prior lines of therapy is a condition with dismal prognosis and a usual survival of only a few weeks. Recently, it has been shown that multiple myeloma with translocation t(11;14) may be exquisitely sensitive to the bcl-2 inhibitor venetoclax.
Aims
Here we report the highly successful therapeutic result of a myeloma patient diagnosed 11 years ago who received 8 prior lines of therapy that included all available therapeutic agents (including thalidomide, lenalidomide, bortezomib, carfilzomib, bendamustine, daratumumab and twice high-dose melphalan with autologous stem cell transplantation). The patient presented at our institution with hypercalcaemia (3.01 mmol/l), cytopenias, ECOG 3 physical condition due to profuse bone pain. Blood smear indicated plasma cell leukemia, flow cytometry analysis confirmed plasma cell leukemia with circulating plasma cells at the level of 14 G/l.
Methods
We are reporting on a clinical case documented with clinical laboratory, FISH and flow cytometry analysis.
Results
Since the patient was known to have broad resistance to available myeloma therapies, however had translocation t(11;14) since diagnosis, after initial zoledronic acid infusion, we elected to administer bortezomib-dexamethason-bendamustine combination with the addition of clarithromycine 500 mg BID and 400 mg daily dose of venetoclax orally. On day 3, the circulatory plasma cells disappeared and grade II tumor lysis syndrome developed (LDH max at 3107 U/l, with manageable hyperuricaemia, hyperkalemia, and hyperphosphatemia). The overall clinical state of the patient was steadily improving, he currently continues to receive venetoclax in monotherapy at the dose level of 400 mg daily. As CYP3A4 inhibition, initially clarithromycine was administered, but after 1 month due to GI symptoms, clarithromycine was switched to fluconazole 100 mg daily that was well tolerated. After 5 month of venetoclax 400 mg OD (only) in this pharmacologically enhanced monotherapy, the patient is ECOG 0, his M-protein is detectable only by immunofixation, free light chains and their ratio are normal, blood counts are in the normal range. Bone marrow aspiration indicated pathological plasma cells below the level of detection of available flow cytometry.
Conclusion
Our case indicates that in secondary plasma cell leukaemia refractory to available prior therapies and exhibiting translocation t(11;14), venetoclax may be a potentially effective salvage therapy. Additionally, pharmacological enhancement of 400 mg daily dose of venetoclax - with CYP3A4 inhibitors clarithromycine or azole antifungal agents - may provide a cost effective alternative to the generally recommended 1200 mg daily dose of this expensive novel medication.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): BCL2, Myeloma, Plasma cells