Treatment of Plasma Cell Leukemia (PCL) with Bortezomib and Thalidomide: A Case Report and Literature Review.
Authors: Caldera Humberto J. , Fernandez Gustavo L. , Leon Baltrucki 
Published: April 2020

Abstract
PCL is an uncommon disease, accounting for only 3% of the monoclonal gammopathies. Due to its low incidence, there are no large trials addressing the treatment for this condition. Treatment approachs are extrapolated from multiple myeloma trials. Specific treatment for PCL is only supported by case reports and few single institutions series.
Compared to myeloma, the prognosis of PCL is very poor, with a median survival of only a few months with standard chemotherapy.
We report a case of a 65 year-old Caucasian woman who presented to our clinic with a six-month history of progressive back pain, severe fatigue, and a 60-pound weight loss. For the previous week, she was unable to walk and had experienced severe nausea and vomiting.
Upon physical examination, she was pale and in obvious distress. Heart rate was 100 bpm, blood pressure 160/73 mmHg, temperature 36.3° C, and respiratory rate 22 bpm. The oral mucosa was dry with no apparent lesions. Lungs were clear to auscultation and heart examination revealed tachycardia, with normal rhythm and no murmurs. Abdominal examination was benign and her neurological exam was non-focal. Extremities showed no peripheral edema.
Laboratory studies:
WBC 2,290/ml (Neu 50%, Lym 13%, Plasma cells 2%)
Hb 5.6 g/dl, Hct 17%, Plat 130,000/ml.
BUN 43 mg/dl, Creat 7.4 mg/dl, Ca 11.2 mg/dl, Beta 2 MG: 18.3 mg/dl. LDH 176 U/L
Total Prot 8.5 g/dl. SPEP: 1.3 gr IgA Kappa monoclonal spike
24- hour urine collection showed significant proteinuria (3 grams)
Bone scan demonstrated diffuse increased uptake at the calvarium, upper extremities, ribs, spine, and pelvic areas. No lytic lesions on bone survey.
Bone marrow biopsy was completely replaced by a population of immature lymphoplasmacytic cells. The peripheral blood demonstrated a population of atypical lymphoid cells (approximately 20% of the circulating lymphocytes), similar to those infiltrating the bone marrow. Flow cytometric studies showed those cells to be CD38+, CD 138+, CD 19−, CD 20−.
Treatment:
Initially treated with hydration, blood transfusions, pamidronate, and dexamethasone. She then received chemotherapy with a modified DT-PACE regimen consisting of: thalidomide 400 mg PO daily for four days, dexamethasone 40 mg PO daily for four days, doxorubicin, cyclophosphamide, and etoposide as continuous IV infusion for four days. She developed prolonged neutropenia and required hospitalization twice for anemia and infectious complications. Renal function and blood counts started to improve, consistent with partial remission.
Due to significant toxicities from her initial treatment, we decided to treat with a combination of bortezomib 1.3 mg/m2 intravenously on days 1, 4, 8, and 11 every 3 weeks plus thalidomide 50 mg by mouth daily for 8 cycles. She tolerated treatments well. No treatment was held or delayed. By the third cycle of bortezomib, her blood counts and renal function returned to normal. A bone marrow biopsy showed complete remission (1% plasma cells). A repeat SPEP was normal. She completed her planned eight courses of bortezomib. Her performance status returned to 100%. She is currently taking thalidomide 100 mg PO daily for maintenance therapy and is in the work-up for autologous stem cell transplant.
We believe that the combination of bortezomib and thalidomide is active in plasma cell leukemia and can be easily given with little toxicity. To our knowledge, this is the first reported evidence of Bortezomib activity in PCL. This strategy should be explored further as it adds to the available therapeutic armamentarium.