Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

Barsegian, Vahé; Möckel, Daniel; Horn, Peter A.; Bockisch, Andreas; Lindemann, Monika

doi:10.1007/s00259-016-3536-9

Cited by 10 publications

(9 citation statements)

References 16 publications

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“…The authors concluded that immune responses against pathogens should remain unaffected by Ra-223. 22 One limitation of this study was whether immune responses were tested after a single or multiple doses of Ra-223. Furthermore, in a preliminary study of 7 patients with mCRPC who received Ra-223, levels of programmed cell death 1 expression decreased on effector memory CD8 þ T cells and memory CD4 þ T cells after Ra-223.…”

Section: Ra-223 Hematologic Effectsmentioning

confidence: 99%

Hematologic Toxicity From Radium-223 Therapy for Bone Metastases in Castration-Resistant Prostate Cancer: Risk Factors and Practical Considerations

Jacene

Gomella

et al. 2018

Clinical Genitourinary Cancer

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Radium-223 dichloride is an α-emitting radiopharmaceutical that localizes to bone matrix and is approved for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. The cumulative impact of Ra-223 and other therapeutic agents for metastatic CRPC on myelosuppression in bone marrow is unknown. The phase 3 randomized, double-blind, placebo-controlled ALSYMPCA trial of Ra-223 in patients with CRPC and symptomatic bone metastases demonstrated a significant improvement in overall survival. Of the 571 patients subsequently followed for 3 years, few in either the Ra-223 or placebo arm experienced hematologic adverse events. Little evidence shows secondary malignancies associated with Ra-223 treatment; only 2 cases of secondary leukemia after Ra-223 treatment were found in the literature. The goals of this review were to summarize safety and efficacy results from clinical trials and institutional safety data pertaining to hematologic adverse events occurring with Ra-223, and to discuss practical management issues.

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Section: Ra-223 Hematologic Effectsmentioning

confidence: 99%

Hematologic Toxicity From Radium-223 Therapy for Bone Metastases in Castration-Resistant Prostate Cancer: Risk Factors and Practical Considerations

Jacene

Gomella

et al. 2018

Clinical Genitourinary Cancer

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“…It is also possible that radium-223 may inhibit B-and T-cell proliferation and function. While a prior small study did not show a negative impact of radium-223 on lymphocyte function (18), that study used different time points to assess immune parameters and did not examine longer term T-cell effects. Thus, radium-223 could have been myelosuppressive, leading to dampened immune responses overall; however, there was no evidence of this detected within the product parameters for sipuleucel-T. Another hypothesis is that genomic alterations could be playing a role, especially if these were not balanced across arms.…”

Section: Discussionmentioning

confidence: 99%

Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer

Marshall

Wang

et al. 2021

Clinical Cancer Research

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Purpose: To investigate if radium-223 increases peripheral immune responses to sipuleucel-T in men with bone-predominant, minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).Methods: 32 patients were randomized 1:1 in this open label, phase 2 multicenter trial. Patients in the control arm received 3 sipuleucel-T treatments, 2 weeks apart. Those in the combination arm received 6 doses of radium-223 monthly, with sipuleucel-T intercalated between the second and fourth doses of radium-223. The primary endpoint was a comparison of peripheral antigen PA2024-specific T cell responses (measured by proliferation index). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and PSA responses. Results:We enrolled 32 patients, followed for a median of 1.6 years. Six weeks after the first sipuleucel-T dose, participants in the control arm had a 3.2-fold greater change in PA2024-specific T cell responses compared to those who received combination treatment (p=0.036). Patients in the combination arm were more likely to have a >50% PSA decline (5 (31%) versus 0 patients; P=0.04), and also demonstrated longer PFS (39 vs 12 weeks; HR 0.32; 95% CI 0.14-0.76) and OS (not-reached vs 2.6 years; HR 0.32; 95% CI 0.08-1.23).

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“…It has been published that radiotherapy with beta and gamma isotopes induces numerical and also functional changes in leukocytes [ 11 , 12 , 13 , 14 , 15 ]. In line with only mild effects of 223 Ra, our group showed that in eleven patients with metastasized, castration-resistant prostate cancer one cycle of treatment with this alpha-emitter did not significantly impair lymphocyte function in vitro [ 16 ]. However, in patients with ankylosing spondylitis treatment with 223 Ra led to a reduction of inflammatory responses (C-reactive protein) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…As compared to a single cycle of 223 Ra therapy, consecutive cycles may have an additive effect on hematopoietic toxicity and may thus lead to detectable effects on in vitro immune function in patients with metastatic prostate cancer. Due to its high sensitivity, the lymphocyte transformation test (LTT) is considered the gold standard for the determination of lymphocyte proliferation after irradiation [ 11 , 12 , 14 , 15 , 19 , 20 , 21 , 22 ] and was also used in our previous study on antimicrobial immune function after one cycle of 223 Ra therapy [ 16 ]. The LTT determines cell proliferation by measuring the incorporation of 3 H-thymidine during DNA duplication, e.g., after stimulation with mitogens or recall antigens.…”

Section: Introductionmentioning

confidence: 99%

Lymphocyte Function at Baseline Could Be a New Predictor of Tumor Burden following Six Cycles of Radium-223 Therapy in Patients with Metastasized, Castration-Resistant Prostate Cancer

Barsegian,

Möckel,

Buehler

et al. 2024

Cancers

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Previous data indicate that one cycle of treatment with radium-223 (223Ra) did not significantly impair lymphocyte function in patients with metastasized, castration-resistant prostate cancer. The aim of the current study was to assess in 21 patients whether six cycles of this therapy had an effect on lymphocyte proliferation and interferon-γ and interleukin (IL)-10 ELISpot results. Lymphocyte proliferation after stimulation with microbial antigens and the production of interferon-γ continuously decreased after six cycles of radionuclide therapy, reaching statistical significance (p < 0.05) at months 1, 2, 4, and/or 6 after therapy. One month after the last cycle of therapy, 67% of patients showed a decrease in tumor burden. The tumor burden correlated negatively with IL-10 secretion at baseline, e.g., after stimulation with tetanus antigen (p < 0.0001, r = −0.82). As determined by receiver operating characteristic (ROC) curve analysis, tetanus-specific IL-10 spots at baseline had the highest predictive value (p = 0.005) for tumor burden at month 6, with an area under the curve (AUC) of 0.90 (sensitivity 100%, specificity 78%). In conclusion, we observed an additive effect of treatment with 223Ra on immune function and found that IL-10 secretion at baseline predicted tumor burden at month 6 after treatment.

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Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

Abstract: The results argue against an impairment of lymphocyte function after Ra therapy. Thus, immune responses against pathogens should remain unaffected.

Cited by 10 publications

References 16 publications

Hematologic Toxicity From Radium-223 Therapy for Bone Metastases in Castration-Resistant Prostate Cancer: Risk Factors and Practical Considerations

Hematologic Toxicity From Radium-223 Therapy for Bone Metastases in Castration-Resistant Prostate Cancer: Risk Factors and Practical Considerations

Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer

Lymphocyte Function at Baseline Could Be a New Predictor of Tumor Burden following Six Cycles of Radium-223 Therapy in Patients with Metastasized, Castration-Resistant Prostate Cancer

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