Evaluating the Impact of Censoring on Progression-Free Survival Comparisons of BCMA-Targeting Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma
Author(s)
Kirsten JM van Nimwegen, PhD1, Suzy Van Sanden, PhD2, Francesca Ghilotti, PhD3, Mary Slavcev, BScPhm4, Eric Ammann, PhD5, Raúl Morano, PhD6, Joris Karel Diels, MSc2.
1Johnson & Johnson, Breda, Netherlands, 2Johnson & Johnson, Beerse, Belgium, 3Johnson & Johnson, Milan, Italy, 4Johnson & Johnson, Toronto, ON, Canada, 5Johnson & Johnson, New Jersey, NJ, USA, 6Johnson & Johnson, Madrid, Spain.
1Johnson & Johnson, Breda, Netherlands, 2Johnson & Johnson, Beerse, Belgium, 3Johnson & Johnson, Milan, Italy, 4Johnson & Johnson, Toronto, ON, Canada, 5Johnson & Johnson, New Jersey, NJ, USA, 6Johnson & Johnson, Madrid, Spain.
OBJECTIVES: The relapsed/refractory multiple myeloma (RRMM) treatment landscape is advancing, with BCMA-targeting bispecific antibodies (BsAbs) teclistamab and elranatamab offering promising therapeutic alternatives for triple-class exposed patients. This study examines comparability of progression-free survival (PFS) outcomes across trials, focusing on informative censoring, a known potential source of bias.
METHODS: Using patient-level data from MajesTEC-1 (teclistamab) and published and digitized data from MagnetisMM-3 (elranatamab), we investigate differences in censoring rules, early censoring rates, and underlying reasons for censoring.
RESULTS: Both clinical studies censored patients who started subsequent anti-MM therapy before disease progression, at the date of last disease evaluation; in MagnetisMM-3, patients were additionally censored on the date of last disease evaluation if a PFS event happened after missing ≥2 disease assessments. Early (24-month) censoring rates differed considerably between teclistamab (7.3%) and elranatamab (22.0%). Since clinical cutoffs occurred ≥2 years after the last patient received their first dose, these censorings are not a result of follow-up duration. Higher early censoring rates for elranatamab likely relate to higher discontinuation due to adverse events versus teclistamab (Table 1) (13.8% and 4.8%, respectively), with older and frailer patients more often discontinuing elranatamab.
CONCLUSIONS: Elranatamab showed higher censoring rates than teclistamab, driven by more patients discontinuing treatment due to adverse events and/or missed disease assessments. As patients with poorer prognoses are more likely to discontinue treatment due to adverse events or miss evaluations, censoring may have been informative, leading to overestimation of PFS. These findings highlight the need to contextualize PFS outcomes when comparing BCMA-targeting bispecific antibodies in relapsed/refractory multiple myeloma. Addressing differences in censoring rates and their causes is crucial to avoid overestimating efficacy, emphasizing the importance of standardized censoring practices and transparent reporting in cross-trial comparisons. In conclusion, cross-trial PFS comparisons between MajesTEC-1 and MagnetisMM-3 should be approached with caution as informative censoring may overestimate elrantamab PFS.
METHODS: Using patient-level data from MajesTEC-1 (teclistamab) and published and digitized data from MagnetisMM-3 (elranatamab), we investigate differences in censoring rules, early censoring rates, and underlying reasons for censoring.
RESULTS: Both clinical studies censored patients who started subsequent anti-MM therapy before disease progression, at the date of last disease evaluation; in MagnetisMM-3, patients were additionally censored on the date of last disease evaluation if a PFS event happened after missing ≥2 disease assessments. Early (24-month) censoring rates differed considerably between teclistamab (7.3%) and elranatamab (22.0%). Since clinical cutoffs occurred ≥2 years after the last patient received their first dose, these censorings are not a result of follow-up duration. Higher early censoring rates for elranatamab likely relate to higher discontinuation due to adverse events versus teclistamab (Table 1) (13.8% and 4.8%, respectively), with older and frailer patients more often discontinuing elranatamab.
CONCLUSIONS: Elranatamab showed higher censoring rates than teclistamab, driven by more patients discontinuing treatment due to adverse events and/or missed disease assessments. As patients with poorer prognoses are more likely to discontinue treatment due to adverse events or miss evaluations, censoring may have been informative, leading to overestimation of PFS. These findings highlight the need to contextualize PFS outcomes when comparing BCMA-targeting bispecific antibodies in relapsed/refractory multiple myeloma. Addressing differences in censoring rates and their causes is crucial to avoid overestimating efficacy, emphasizing the importance of standardized censoring practices and transparent reporting in cross-trial comparisons. In conclusion, cross-trial PFS comparisons between MajesTEC-1 and MagnetisMM-3 should be approached with caution as informative censoring may overestimate elrantamab PFS.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO108
Topic
Clinical Outcomes, Methodological & Statistical Research
Topic Subcategory
Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy
Disease
Oncology, Rare & Orphan Diseases