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Home All Specialties Chronic Disease

Targeted autologous transfusion may aid advanced refractory multiple myeloma

byMatthew Lin, MDandShaidah Deghan, MSc. MD
September 11, 2015
in Chronic Disease, Oncology
Reading Time: 2 mins read
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1. A sustained decrease of up to 12 months in serum IgA measurements was demonstrated after administration of CTL019 transfusion in a patient with multiple myeloma (MM).

2. A sustained decrease of up to 12 months in malignant plasma cells on bone marrow biopsy was demonstrated after administration of CTL019 transfusion. 

Evidence Rating: 4 (Below average)   

Study Rundown: MM is a B-lineage malignancy comprised primarily of terminally differentiated CD19-negative plasma cells. However, a handful of reports have suggested that a subset of drug-resistant MM clones are in fact, CD19 positive. In this study, CTL019 therapy, or the use of autologous T-cells that are genetically modified to express proteins, was used to target B-cell CD19.  In this case report, the authors described the clinical effects of CTL019 therapy in combination with myeloablation with stem cell transplantation in a 43-year-old female patient with refractory IgA kappa MM. The patient in question demonstrated a significant reduction in MM burden after CTL019 therapy in terms of both a decrease in monoclonal IgA concentration and malignant plasma cell presence in the bone marrow. The utility of this case report is that it has highlighted the potential benefits of a previously studied therapy being used in a novel way to treat MM. The study is limited by virtue of being a case report. While the data provides several novel observations, it is not generalizable and is subject to bias.

Click to read the study, published today in NEJM

Relevant Reading: Chimeric antigen receptor T-cell immunotherapy tackles blood cancers 

In-Depth [case report]: In this case report, the authors described the effects of autologous CTL019 therapy in a patient with advanced, refractory MM after myeloablation with melphalan and autologous stem cell transplantation. The patient, a 43-year-old female with IgA kappa MM, was initially treated with lenalidomide, bortezomib and dexamethasone, which failed to adequately stop disease progression. A second line treatment with myeloablation and autologous stem-cell transplantation with lenalidomide maintenance was also unsuccessful, prompting enrollment in a CTL019 trial. Key post-treatment changes were most notable in IgA measurements and marrow biopsies, which were performed at 42 and 100 days after transplantation and also when clinically indicated. Within 50 days after CTL019 transplant, monoclonal IgA had fallen below quantifiable levels (<7 mg/dL), with the effect enduring up to 12 months. The patient’s bone marrow biopsy at baseline was notable for >95% malignant plasma cells, while bone marrow biopsy at day 100 from transplantation demonstrated 1-2% overall cellularity without malignant plasma cells. The researchers also measured the presence of CTL019 and found that CTL019 cells were peripherally identifiable up to 47 days from infusion. This suggests that the long-term presence of CTL019 cells is not required for sustained response. 

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Image: PD

©2015 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.

Tags: multiple myeloma
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