181 NK Cell Recovery and Costimulatory Molecule Profiles After Autologous Hematopoietic Cell Transplantation (HCT) in Multiple Myeloma (MM) Patients

Track: Contributed Abstracts
Wednesday, February 13, 2013, 6:45 PM-7:45 PM
Hall 1 (Salt Palace Convention Center)
Myo Htut, MD , Hematology/HCT, City of Hope, Duarte, CA
Ghislaine Gallez-hawkins , Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
Joycelynne Palmer, PhD , Information Sciences, City of Hope, Duarte, CA
Ricardo Spielberger, MD , City of Hope National Medical Center, Duarte, CA
Pablo M Parker, MD , City of Hope National Med Ctr, Duarte, CA
Len T Farol, MD , Kaiser Permanente/City of Hope, Duarte, CA
Anne Franck , Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
Laetitia Jeannet , Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, CA
Eunicia Reburiano , Division of Biostatistics, City of Hope National Medical Center, Duarte, CA;
Valerie Jimenez , Division of Biostatistics, City of Hope National Medical Center, Duarte, CA;
Lupe Duarte , Division of Biostatistics, City of Hope National Medical Center, Duarte, CA
Andy Dagis , Division of Biostatistics, City of Hope National Medical Center, Duarte, CA
Firoozeh Sahebi , Kaiser Permanente Southern California, Duarte, CA
Chatchada Karanes, MD , Hematology/HCT, City of Hope, Duarte, CA
Stephen J. Forman, MD , Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA
Amrita Y. Krishnan, MD , City of Hope Medical Center, Duarte, CA
John Zaia , Virology, Beckman Research Institute of City of Hope, Duarte, CA

NK cell recovery and costimulatory molecule profiles after autologous hematopoietic cell transplantation (HCT) in multiple myeloma (MM) patients

Background:  Enhanced immune responses post autologous HCT is known to be beneficial for long term disease control in MM. Early responses are mediated by NK cells and alternate inhibitory/stimulatory pathways that include the costimulatory molecules. This pilot study assesses the expression of NK cytolytic receptor (CD16) as well as the stimulatory (OX-40, ICOS, 4-1BB, CD28, NKG2D) and inhibitory (PD-1 and CTLA-4) molecules on NK cells after auto-HCT in MM patients.

Methods: 22 patients with MM undergoing HCT, median age 59.6 years (36 - 71.4), were included in the study. Peripheral blood samples were taken 3 days prior to HCT and 14, 30, 60, 90, 180 days after HCT.  At d180 post-HCT, 18/22 patients were receiving lenalidomide with d86 as median start date. NK cells and their costimulatory molecules were evaluated by flowcytometry using 2 six color panels of antibodies. One way ANOVA test (SAS9.3) and Kruskal-Wallis test (non-parametric) were applied to analyze the data using the Graphpad Software.

Results:

 

Pre-HCT

d180

Partial Response or worse (≤   PR)

9

9

Very Good Partial Response or better (VGPR)

10

0

Complete Remission (CR)

3

13

The percent NK cell was highest (median: 20% of total lymphocytes) at d14 (p: 0.0001) compared to pre and post HCT levels and reached baseline at d 60. The percent NK cell was higher in ≥VGPR (n=13) [median: 14.34% (6.29-28.17) and 16.08 % (7.26-31.19)] compared to ≤PR (n=9) [median: 8.17% (4.01- 17.3) and 7.34 %( 5.79- 47.8)] respectively at d 90 (p-0.019) and d 180 (p-0.045). The NK cells expressing CD 16 was 12.2 times higher in patients after receiving Lenalidomide (n=18) (p-0.05) compared to pre-lenalidomide time point.

Conclusion: After auto-HCT, NK cell recovery was reached at 60 days after HCT and was higher in ≥VGPR compared to ≤PR group at later times. This observation could indicate enhanced host NK cell immune response against MM. Lenalidomide therapy increased the percent of NK/ CD 16+ cells that mediates ADCC immune response. Future clinical trials will explore therapies that increase NK cell cytolytic responses to MM cancer cells.

 

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