abt-199 and Leukemia--Plasma-Cell

BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.

Topics: Bortezomib; Dexamethasone; Female; Humans; Lenalidomide; Leukemia, Plasma Cell; Transplantation, Homologous

Topics: Antineoplastic Agents; Bridged Bicyclo Compounds, Heterocyclic; Humans; Induction Chemotherapy; Leukemia, Plasma Cell; Proto-Oncogene Proteins c-bcl-2; Sulfonamides

Plasma cell leukemia (PCL) is a rare but aggressive variant of multiple myeloma (MM) with a poor prognosis. Due to the limited number of prospective clinical trials studying PCL, treatment options are often extrapolated from data available for the treatment of MM. Venetoclax has recently demonstrated antimyeloma activity in patients with relapsed/refractory MM carrying the t(11;14) translocation. However, few cases have reported the analogous efficacy of venetoclax in PCL.. A 64-year-old Caucasian male developed relapsed PCL despite treatment with hyperCD (hyperfractionated cyclophosphamide and dexamethasone) and Dara-KRd (daratumumab, carfilzomib, lenalidomide, dexamethasone). Due to the refractory nature of his disease and the presence of a t(11:14) translocation, the patient was subsequently initiated on venetoclax 400 mg daily and dexamethasone 4 mg once weekly.. The patient achieved a complete response by International Myeloma Working Group criteria three months after initiating venetoclax-dexamethasone, including a repeat bone marrow biopsy that showed no abnormal plasma cells. He successfully underwent consolidation with melphalan-based autologous stem cell transplantation. He remains disease-free 9 months after venetoclax initiation.. Combination all-oral therapy with venetoclax and dexamethasone can induce deep hematologic responses in patients with relapsed/refractory PCL carrying the t(11;14) translocation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Plasma Cell; Male; Middle Aged; Multiple Myeloma; Prospective Studies; Transplantation, Autologous

A 70-year-old man with medical history of IgG kappa multiple myeloma, initially diagnosed in 2017, underwent induction therapy with carfilzomib, lenalidomide and dexamethasone followed by autologous haematopoietic stem cell transplantation. Nine months following transplant, disease relapsed in the form of plasma cell leukaemia. Fluorescent in situ hybridisation of malignant plasma cells revealed t(11;14). A combination therapy including venetoclax was used based on efficacy data for Bcl-2 inhibitor venetoclax from available early-phase clinical trials in patients with relapsed multiple myeloma with t(11;14) and other published case studies. Unfortunately, the disease was primary refractory, and after further ineffective therapies, the patient did not have a successful outcome.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; In Situ Hybridization, Fluorescence; Lenalidomide; Leukemia, Plasma Cell; Male; Multiple Myeloma; Neoplasm Recurrence, Local; Oligopeptides; Oncogene Proteins, Fusion; Sulfonamides; Translocation, Genetic; Transplantation, Autologous; Treatment Failure

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Dexamethasone; Humans; Leukemia, Plasma Cell; Male; Sulfonamides

Secondary plasma cell leukemia (sPCL) patients typically are either refractory to conventional therapies or have short remissions to drug regimens used in multiple myeloma (MM), which highlights sPCL's aggressive nature and association with advanced stage disease. t(11,14) is correlated with increased BCL-2 expression, which makes it a cytogenic marker of interest for use of the BCL-2 inhibitor venetoclax. Little data of venetoclax's use has been published in plasma cell leukemia. We present a case of a refractory/relapsed sPCL patient displaying t(11,14) who achieved a very good partial response (VGPR) from venetoclax therapy in combination with dexamethasone and bortezomib.. Our case describes a 67-year-old male initially diagnosed with IgG kappa MM in 2013, which transformed into non-secretory secondary plasma cell leukemia. Over a two-year period, despite responses to various therapies, the patient continued to experience relapses and exhausted options of novel agents seen in MM treatment. The patient was started on venetoclax in combination with bortezomib and oral dexamethasone.. Due to the patient's disease transformation into a non-secretory form of sPCL, PET/CT scans were relied upon to monitor disease progression. The PET/CT scan after three months of venetoclax combination treatment showed a very good partial response to therapy, with near resolution of metabolically active osseous disease.. The success of venetoclax-based therapy in achieving a very good partial response suggests its utility in relapsed/refractory sPCL patients, who have exhausted various combinations of drug regimens used in treatment of MM and have historically poor survival outcomes.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Bridged Bicyclo Compounds, Heterocyclic; Dexamethasone; Humans; Leukemia, Plasma Cell; Male; Positron Emission Tomography Computed Tomography; Recurrence; Sulfonamides; Treatment Outcome

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Combined Modality Therapy; Drug Resistance, Neoplasm; Female; Humans; Leukemia, Plasma Cell; Multiple Myeloma; Neoplasm Proteins; Neoplasms, Second Primary; Plasma Cells; Plasmapheresis; Progression-Free Survival; Proto-Oncogene Proteins c-bcl-2; Sulfonamides; Translocation, Genetic

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Bridged Bicyclo Compounds, Heterocyclic; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Plasma Cell; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Proteins; Neoplasm, Residual; Proto-Oncogene Proteins c-bcl-2; Recurrence; Sulfonamides; Translocation, Genetic; Vincristine

Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell (PC) malignancy, multiple myeloma (MM). It has been commonly associated with the presence of a chromosome translocation involving the immunoglobulin heavy chain (IgH) locus on 14q32, that is t (11;14). Results from early phase clinical trials utilizing the selective Bcl-2 inhibitor, venetoclax, as a single agent in patients with relapsed MM have had remarkable efficacy among patients with t (11;14) abnormality. The present case demonstrates the ability of a combination regimen incorporating Bcl-2 inhibition with daratumumab, bortezomib, venetoclax, and dexamethasone to induce a rapid and very deep hematologic response in a pPCL patient with t (11;14), even in a setting of very refractory disease. This case highlights the need to further study Bcl-2 inhibition-based therapy as an option for therapy in patients with pPCL with t (11;14).

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone Marrow; Bridged Bicyclo Compounds, Heterocyclic; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Drug Resistance, Neoplasm; Female; Humans; Immunoglobulin kappa-Chains; Leukemia, Plasma Cell; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Retreatment; Sulfonamides; Translocation, Genetic; Treatment Outcome