Session: 203. Lymphocytes and Acquired or Congenital Immunodeficiency Disorders: Poster III
Hematology Disease Topics & Pathways:
Research, Autoimmune disorders, Translational Research, Clinical Research, Diseases, Immune Disorders, Lymphoid Malignancies, Myeloid Malignancies
5162 Mass General Brigham patients with a GG genotype (corresponding to high thymopoiesis) were compared with 5650 patients with an AA genotype (predicting low thymopoiesis) to calculate the incidence rate of all cancers and individual cancer subtypes. Manual chart review was also conducted to evaluate survival, relapse, risk of progression, and response to therapy among patients of different rs2204985 genotypes with myelodysplastic syndrome (N=68 patients), chronic lymphocytic leukemia (CLL; N=50 patients), gastroesophageal cancers (N=182 patients), lung cancers (N=57 patients), and melanoma (N=40 patients). Patients within the two groups had similar age, race, sex, smoking history, kidney function, and A1c.
Compared to patients with the high thymopoiesis genotype (GG), demographically-similar patients with the low thymopoiesis genotype (AA) had a higher risk of developing all cancers over a period of 10 years (incidence rate ratio, IRR [95% confidence interval]: 1.1 [1.05-1.14], p<0.001). Patients with the AA genotype had a higher risk of developing a diverse host of cancers, including melanoma (1.14 [1.07-1.23], p<0.001) and genitourinary cancers (1.16 [1.02-1.33], p=0.02) compared with patients with the GG genotype.
Clinical outcomes of demographically-similar patients with cancer also differed between groups. Among patients with low thymopoiesis, progression free survival was significantly inferior and the numbers of relapses were greater compared to patients with high thymopoiesis across myelodysplastic syndrome (2.1 vs 3.3 years, p=0.02; 1.0 vs 0.5 relapses per patient, p=0.03), CLL (4.3 vs 8.8 years, p<0.001; 1.7 vs 0.3 relapses per patient, p=0.004), gastroesophageal cancers (2.6 vs 4.5 years, p<0.001; 1.7 vs 0.8 relapses per patient, p=0.02), lung cancers (0.83 vs 1.24 years, p=0.01; 3.7 vs 2.2 relapses per patient, p=0.003), and melanoma (0.91 vs 2.1 years, p<0.001; 6.4 vs 3.1 relapses per patient, p=0.004). Among patients with low thymopoiesis, the numbers of metastases and immune-related adverse events (irAEs) in response to therapy were greater compared with patients with high thymopoiesis across gastroesophageal cancers (5.2 vs 3.1 metastases, p=0.002; 0.81 vs 0.29 irAEs per patient, p=0.007), lung cancers (8.5 vs 2.7 metastases, p<0.001; 1.9 vs 0.89 irAEs per patient, p=0.03), and melanoma (7.5 vs 2.5 metastases, p<0.001; 5.4 vs 1.6 irAEs per patient, p<0.001). Finally, progression of myelodysplastic syndrome to leukemia and transformation of CLL to lymphoma were also more frequent outcomes among patients with low thymopoiesis (50.0% vs 20.6% and 56.3% vs 9.7% of patients progressed to leukemia [p=0.02] and lymphoma [p<0.001], respectively).
More robust thymopoiesis associated with the rs2204985 GG genotype correlates with both reduced development of cancer in adults and improved outcomes across a variety of hematologic and solid cancers. These data support the importance of sustained thymus function to health throughout adult life particularly in cancer control.
Disclosures: Scadden: Editas Medicine: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Lightning Biotherapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Sonata Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Carisma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Garuda Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Clear Creek Bio: Current holder of stock options in a privately-held company; VCanBio: Consultancy.
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