Immune signatures associated with improved progression-free and overall survival for myeloma patients treated with AHSCT

Ho, Christine M.; McCarthy, Philip L.; Wallace, Paul K.; Zhang, Yali; Fora, Ahmad; Mellors, Patrick; Tario, Joseph D.; McCarthy, Benjamin; Chen, George L.; Holstein, Sarah A.; Balderman, Sophia R.; Cao, Xuefang; Paiva, Bruno; Hahn, Theresa

doi:10.1182/bloodadvances.2017005447

Cited by 43 publications

(46 citation statements)

References 30 publications

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“…1,3 Early studies observed that long-term disease-free survival (DFS) of leukemia patients who received ab T-cell-depleted (TCD) partially mismatched related donor (PMRD) transplants had high numbers of circulating gd T cells after HSCT. 4,5 More recent studies with non-TCD PMRD 6 and autologous HSCT 7 further corroborated these findings, describing an improved survival in patients with higher gd T-cell counts posttransplantation. These studies suggested that the recovery of gd T cells after HSCT is critical for an efficient GVL effect 3 and possibly to control infections, 8 helping to pave the way to a more broad application of graft manipulation strategies.…”

Section: Introductionmentioning

confidence: 72%

“…Eleven studies were used in meta-analysis, enrolling 919 patients. [4][5][6][7][8]17,[53][54][55][56][57] From those reports, 8 evaluated gd T-cell reconstitution after HSCT and 3 evaluated gd T-cell content in the graft ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…aGVHD incidence was reported in 7 studies, 4,6,17,[53][54][55]57 and the number of relapses was reported in 7 studies. 4,5,7,[53][54][55][56] Viral infections after HSCT were reported in 6 studies; CMV reactivation was reported in 5, 4,6,53,55,56 whereas Epstein-Barr virus (EBV) reactivation in 1 study. 8 OS was reported in 5 studies, 4,7,53,55,56 whereas DFS was reported in 4.…”

Section: Resultsmentioning

confidence: 99%

“…4,5,7,[53][54][55][56] Viral infections after HSCT were reported in 6 studies; CMV reactivation was reported in 5, 4,6,53,55,56 whereas Epstein-Barr virus (EBV) reactivation in 1 study. 8 OS was reported in 5 studies, 4,7,53,55,56 whereas DFS was reported in 4. 4,5,54,55 gd T-cell content was defined primarily by anti-pan gd T-cell receptor marker, despite some studies using anti-Vd2 8 or anti-Vd1.…”

Section: Resultsmentioning

confidence: 99%

“…6,57 Six studies stratified patients using gd T-cell percentage, 5,6,53,54,56,57 whereas 5 used absolute counts. 4,7,8,17,55 Three studies checked the intragraft gd T-cell content, 17,53,57 whereas 8 studies evaluated its immune reconstitution after HSCT and used 100 days posttransplantation as the median sampling timepoint for group definition. [4][5][6][7][8][54][55][56] The risk of bias and confounding assessment depicted that all studies reported well-documented patient's baseline characteristics, were selected appropriately, and had outcome measures consistently defined across all participants (supplemental Table 1).…”

Section: Resultsmentioning

confidence: 99%

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Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis

2019

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Allogeneic hematopoietic stem cell transplantation (HSCT) using αβ T-/B-cell–depleted grafts recently emerged as a transplant strategy and highlighted the potential role of γδ T cells on HSCT outcomes. Our aim was to scrutinize available evidence of γδ T-cell impact on relapse, infections, survival, and acute graft-versus-host disease (aGVHD). We performed a systematic review and meta-analysis of studies assessing γδ T cells in HSCT. We searched PubMed, Web of Science, Scopus, and conference abstracts from inception to March 2019 for relevant studies. We included all studies that assessed γδ T cells associated with HSCT. Data were extracted independently by 2 investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies. Primary outcome was disease relapse. We also assessed infections, survival, and aGVHD incidence. The review was registered with PROSPERO (CRD42019133344). Our search returned 2412 studies, of which 11 (919 patients) were eligible for meta-analysis. Median follow-up was 30 months (interquartile range, 22-32). High γδ T-cell values after HSCT were associated with less disease relapse (risk ratio [RR], 0.58; 95% confidence interval [95% CI], 0.40-0.84; P = .004; I2 = 0%), fewer viral infections (RR, 0.59; 95% CI, 0.43-0.82; P = .002; I2 = 0%) and higher overall (HR, 0.28; 95% CI, 0.18-0.44; P < .00001; I2 = 0%) and disease-free survivals (HR 0.29; 95% CI, 0.18-0.48; P < .00001; I2 = 0%). We found no association between high γδ T-cell values and aGVHD incidence (RR, 0.72; 95% CI, 0.41-1.27; P = .26; I2 = 0%). In conclusion, high γδ T cells after HSCT is associated with a favorable clinical outcome but not with aGVHD development, suggesting that γδ T cells have a significant effect on the success of HSCT. This study was registered with PROSPERO as #CRD42019133344.

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Section: Introductionmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis

2019

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The immune system in multiple myeloma and precursor states: Lessons and implications for immunotherapy and interception

Dhodapkar

2022

American J Hematol

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Multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS) are distinct disorders that likely originate in the setting of chronic immune activation. Evolution of these lesions is impacted by cross‐talk with both innate and adaptive immune systems of the host. Harnessing the immune system may, therefore, be an attractive strategy to prevent clinical malignancy. While clinical MM is characterized by both regional and systemic immune suppression and paresis, immune‐based approaches, particularly redirecting T cells have shown remarkable efficacy in MM patients. Optimal application and sequencing of these new immune therapies and their integration into clinical MM management may depend on the underlying immune status, in turn impacted by host, tumor, and environmental features. Immune therapies carry the potential to achieve durable unmaintained responses and cures in MM.

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Continuous lenalidomide and low‐dose dexamethasone in patients with transplant‐ineligible newly diagnosed MM: FIRST trial subanalysis of Canadian/US patients

Belch¹,

Bahlis

White

et al. 2020

Cancer Medicine

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The phase 3 FIRST trial demonstrated significant improvement in progression‐free survival (PFS) and overall survival (OS) with an immune‐stimulatory agent, lenalidomide, in combination with low‐dose dexamethasone until disease progression (Rd continuous) vs melphalan +prednisone + thalidomide (MPT) in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM). Rd continuous similarly extended PFS vs fixed‐duration Rd for 18 cycles (Rd18). Outcomes in the Canadian/US subgroup (104 patients per arm) are reported in this analysis. Rd continuous demonstrated a significant improvement in PFS vs MPT (median, 29.3 vs 20.2 months; HR, 0.69 [95% CI, 0.49‐0.97]; p = 0.03326) and an improvement vs Rd18 (median, 21.9 months). Median OS was 56.9 vs 46.8 months with Rd continuous vs MPT ( p = 0.15346) and 59.5 months with Rd18. The overall response rate was higher with Rd continuous and Rd18 (78.8% and 79.8%) vs MPT (65.4%). In the 49.0%, 52.9%, and 29.8% of patients with at least very good partial response in the Rd continuous, Rd18, and MPT arms, respectively, the median PFS was 56.0, 30.9, and 40.2 months, respectively. The most common grade 3/4 treatment‐emergent adverse events were neutropenia (28.4%, 30.1%, and 52.0%), anemia (23.5%, 21.4%, and 23.5%), and infections (37.3%, 30.1%, and 24.5%) with Rd continuous, Rd18, and MPT, respectively. These results were consistent with those in the intent‐to‐treat population, confirming the benefit of Rd continuous vs MPT in the Canadian/US subgroup and supporting the role of Rd continuous as a standard of care for transplant‐ineligible patients with NDMM.

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Immune signatures associated with improved progression-free and overall survival for myeloma patients treated with AHSCT

Abstract: Key Points Specific immune phenotypes were predictive of long-term survival for MM patients undergoing transplantation. MRD status and use of maintenance therapy were associated with unique immune profiles predictive of outcome.

Cited by 43 publications

References 30 publications

Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis

Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis

The immune system in multiple myeloma and precursor states: Lessons and implications for immunotherapy and interception

Continuous lenalidomide and low‐dose dexamethasone in patients with transplant‐ineligible newly diagnosed MM: FIRST trial subanalysis of Canadian/US patients

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