CoChat
Sign Up
Cited by 134

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Lovo‐cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB ‐206 study

Kanter, Julie, Thompson, Alexis A., Pierciey, Francis J., Hsieh, Matthew, Uchida, Naoya, Leboulch, Philippe, Schmidt, Manfred, Bonner, Melissa, Guo, Ruiting, Miller, Alex, Ribeil, Jean‐Antoine, Davidson, David, Asmal, Mohammed, Walters, Mark C., Tisdale, John F.·2023·American Journal of Hematology
DOI 10.1002/ajh.26741PMC PMC10092845
Open this paper in CoChat — free account

Abstract

lovo‐cel (bb1111; LentiGlobin for sickle cell disease [SCD]) gene therapy (GT) comprises autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified β‐globin gene (β A‐T87Q ) to produce anti‐sickling hemoglobin (HbA T87Q ). The efficacy and safety of lovo‐cel for SCD are being evaluated in the ongoing phase 1/2 HGB‐206 study ( ClinicalTrials.gov : NCT02140554). The treatment process evolved over time, using learnings from outcomes in the initial patients to optimize lovo‐cel's benefit–risk profile. Following modest expression of HbA T87Q in the initial patients (Group A, n = 7), alterations were made to the treatment process for patients subsequently enrolled in Group B ( n = 2, patients B1 and B2), including improvements to cell collection and lovo‐cel manufacturing. After 6 months, median Group A peripheral blood vector copy number (≥0.08 c/dg) and HbA T87Q levels (≥0.46 g/dL) were inadequate for substantial clinical effect but stable and sustained over 5.5 years; both markedly improved in Group B (patient B1: ≥0.53 c/dg and ≥2.69 g/dL; patient B2: ≥2.14 c/dg and ≥6.40 g/dL, respectively) and generated improved biologic and clinical efficacy in Group B, including higher total hemoglobin and decreased hemolysis. The safety of the lovo‐cel for SCD treatment regimen largely reflected the known side effects of HSPC collection, busulfan conditioning regimen, and underlying SCD; acute myeloid leukemia was observed in two patients in Group A and deemed unlikely related to insertional oncogenesis. Changes made during development of the lovo‐cel treatment process were associated with improved outcomes and provide lessons for future SCD GT studies.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/ajh.26741

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Figures

FIGURE 1 Overview of the lovo‐cel treatment process and HGB‐206 study design evolution. (A) Gene therapy treatment process of lovo‐cel for SCD. (B) Treatment process evolution. *The target TNC for BMH was ≥6 × 108/kg per patient. The Group B1 patient received lovo‐cel produced using both the original and refined manufacturing process, and the Group B2 patient received lovo‐cel produced using only the refined manufacturing process. Both Group B patients received lovo‐cel manufactured from HSPCs collected using BMH; however, the Group B2 patient also underwent rescue HSPC collection by plerixafor mobilization/apheresis for the exploratory evaluation of its safety and enhancement of the lovo‐cel manufacturing process. The Group B2 patient did not receive lovo‐cel manufactured from HSPCs collected using plerixafor mobilization/apheresis. Figure adapted from N Engl J Med, Kanter, J. et al., Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease, 386, 617–628. Copyright © 2022 Massachusetts Medical Society. Reprinted with permission. 16 AUC, area under the curve; BMH, bone marrow harvest; DP, drug product; HbAT87Q, Hb with modified β‐globin gene (βA‐T87Q); HbS, sickle Hb; HSPC, hematopoietic stem and progenitor cell; LVV, lentiviral vector; RBC, red blood cell; SCD, sickle cell disease; TNC, total nucleated cell count. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 1 Overview of the lovo‐cel treatment process and HGB‐206 study design evolution. (A) Gene therapy treatment process of lovo‐cel for SCD. (B) Treatment process evolution. *The target TNC for BMH was ≥6 × 108/kg per patient. The Group B1 patient received lovo‐cel produced using both the original and refined manufacturing process, and the Group B2 patient received lovo‐cel produced using only the refined manufacturing process. Both Group B patients received lovo‐cel manufactured from HSPCs collected using BMH; however, the Group B2 patient also underwent rescue HSPC collection by plerixafor mobilization/apheresis for the exploratory evaluation of its safety and enhancement of the lovo‐cel manufacturing process. The Group B2 patient did not receive lovo‐cel manufactured from HSPCs collected using plerixafor mobilization/apheresis. Figure adapted from N Engl J Med, Kanter, J. et al., Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease, 386, 617–628. Copyright © 2022 Massachusetts Medical Society. Reprinted with permission. 16 AUC, area under the curve; BMH, bone marrow harvest; DP, drug product; HbAT87Q, Hb with modified β‐globin gene (βA‐T87Q); HbS, sickle Hb; HSPC, hematopoietic stem and progenitor cell; LVV, lentiviral vector; RBC, red blood cell; SCD, sickle cell disease; TNC, total nucleated cell count. [Color figure can be viewed at wileyonlinelibrary.com]CC BY-NC-ND · PubMed Central
FIGURE 2 Hb fractions over time and at last visit following lovo‐cel infusion. (A) PB VCN. (B) HbAT87Q. (C) Hb fractions at last visit. (D) Total Hb. (E) HbF. Dashed lines indicate Group A patients 1 and 2 who, for an extended period post‐engraftment, were receiving regular transfusions and hydroxyurea; pRBC transfusion volume, day of transfusion, and transfusion type are reported in Table S3.*Patient diagnosed with AML in 2021. 27 †Patient diagnosed with myelodysplastic syndrome/AML in 2018 26 ; data for efficacy endpoints are shown up to last visit prior to diagnosis of malignancy. ‡Received regular transfusions and hydroxyurea for an extended period after lovo‐cel infusion, including the year prior to last visit; packed red blood cell transfusion volume, day of transfusion, and transfusion type are reported in Table S3. §Received a transfusion at last follow‐up. Total Hb baseline values (panel C) were defined as the average of the two most recent Hb assessments at/prior to screening; assessments were separated by >1 month, ≤24 months before informed consent, and excluded any patients who received a pRBC transfusion ≤3 months of each assessment; for patients receiving chronic transfusions, Hb values ≤24 months before the start of a regular transfusion program and separated by >1 month were used. AML, acute myeloid leukemia; c/dg, copies per diploid genome; Hb, hemoglobin; HbA, adult Hb; HbAT87Q, Hb with modified β‐globin gene (βA‐T87Q); HbF, fetal Hb; HbS, sickle Hb; M, month; pt, patient; PB, peripheral blood; pRBC, packed red blood cell; pt, patient; VCN, vector copy number. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2 Hb fractions over time and at last visit following lovo‐cel infusion. (A) PB VCN. (B) HbAT87Q. (C) Hb fractions at last visit. (D) Total Hb. (E) HbF. Dashed lines indicate Group A patients 1 and 2 who, for an extended period post‐engraftment, were receiving regular transfusions and hydroxyurea; pRBC transfusion volume, day of transfusion, and transfusion type are reported in Table S3.*Patient diagnosed with AML in 2021. 27 †Patient diagnosed with myelodysplastic syndrome/AML in 2018 26 ; data for efficacy endpoints are shown up to last visit prior to diagnosis of malignancy. ‡Received regular transfusions and hydroxyurea for an extended period after lovo‐cel infusion, including the year prior to last visit; packed red blood cell transfusion volume, day of transfusion, and transfusion type are reported in Table S3. §Received a transfusion at last follow‐up. Total Hb baseline values (panel C) were defined as the average of the two most recent Hb assessments at/prior to screening; assessments were separated by >1 month, ≤24 months before informed consent, and excluded any patients who received a pRBC transfusion ≤3 months of each assessment; for patients receiving chronic transfusions, Hb values ≤24 months before the start of a regular transfusion program and separated by >1 month were used. AML, acute myeloid leukemia; c/dg, copies per diploid genome; Hb, hemoglobin; HbA, adult Hb; HbAT87Q, Hb with modified β‐globin gene (βA‐T87Q); HbF, fetal Hb; HbS, sickle Hb; M, month; pt, patient; PB, peripheral blood; pRBC, packed red blood cell; pt, patient; VCN, vector copy number. [Color figure can be viewed at wileyonlinelibrary.com]CC BY-NC-ND · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 7 references

Research works printed but not linked: 28

  1. 10.1182/blood-2007-03-079665 · DOI
  2. Platt OS, 1984, Hydroxyurea increases fetal hemoglobin production in sickle cell anemia, Trans Assoc Am Phys, 97, 268
  3. BradtPS E. Synnott P. Chapman R. Rind D.M.;Pearson S.Crizanlizumab Voxelotor and L‐glutamine for sickle cell disease: effectiveness and value. Institute for Clinical and Economic Review;2020.
  4. 10.1111/bjh.12413 · DOI · Paper page
  5. 10.1016/j.bbmt.2015.10.017 · DOI
  6. 10.1016/j.bbmt.2009.10.005 · DOI
  7. 10.1182/asheducation-2011.1.273 · DOI
  8. 10.1111/ejh.13546 · DOI
  9. 10.1073/pnas.92.7.3014 · DOI · Paper page
  10. 10.1016/j.omtm.2020.04.013 · DOI
  11. 10.1038/s41591-021-01650-w · DOI
  12. 10.1089/hum.2016.007 · DOI · Paper page
  13. 10.1016/j.stem.2017.10.010 · DOI
  14. 10.15252/emmm.201809958 · DOI
  15. 10.1182/blood-2019-129124 · DOI
  16. 10.1002/ajh.25867 · DOI
  17. 10.1182/blood.V126.23.202.202 · DOI
  18. 10.1164/rccm.201401-0065ST · DOI
  19. 10.1182/bloodadvances.2019001330 · DOI · Paper page
  20. 10.1056/NEJMoa2109167 · DOI · Paper page
  21. 10.1053/bbmt.2002.v8.pm12374452 · DOI
  22. 10.1111/j.1365-2141.1995.tb05199.x · DOI
  23. Locatelli F, 1996, Hematopoietic and immune recovery after transplantation of cord blood progenitor cells in children, Bone Marrow Transplant, 18, 1095
  24. 10.1172/JCI109286 · DOI
  25. 10.1016/j.beha.2019.02.004 · DOI
  26. 10.1182/blood-2017-05-783233 · DOI · Paper page
  27. 10.1177/0141076816651037 · DOI · Paper page
  28. 10.1111/bjh.15902 · DOI

Cited by

See all 134

Metadata

Authors
Kanter, J., Thompson, A. A., Pierciey, F. J., Hsieh, M., Uchida, N., Leboulch, P., Schmidt, M., Bonner, M., Guo, R., Miller, A., Ribeil, J., Davidson, D., Asmal, M., Walters, M. C., & Tisdale, J. F.
Venue
American Journal of Hematology
Publisher
Wiley
Published
2022-10-10
Volume
98
Issue
1
Pages
11-22
ISSN
  • 0361-8609
  • 1096-8652
DOI
10.1002/ajh.26741
PMC
PMC10092845
Cited by
134
References
7
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Funders
bluebird bio

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Lovo‐cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB ‐206 study. https://app.cochat.ai/papers/10.1002/ajh.26741
The paper
Kanter, J., Thompson, A. A., Pierciey, F. J., Hsieh, M., Uchida, N., Leboulch, P., Schmidt, M., Bonner, M., Guo, R., Miller, A., Ribeil, J., Davidson, D., Asmal, M., Walters, M. C., & Tisdale, J. F. (2023). Lovo‐cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB ‐206 study. American Journal of Hematology. https://doi.org/10.1002/ajh.26741