Contributions
Abstract: EP972
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Patients with relapsed/refractory multiple myeloma (RRMM) who are triple-class exposed to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs) and anti-CD38 monoclonal antibodies (MoABs) have few treatment options available and poor outcomes (Gandhi et al., Leukemia, 2019). Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell (CAR-T) therapy, is studied in CARTITUDE-1, an open-label, single arm phase 1b/2 clinical trial assessing safety and efficacy of cilta-cel in adult patients with triple-class exposed RRMM. In absence of a comparator arm in CARTITUDE-1, comparison of trial outcomes versus an external cohort of similar patients allows to quantify clinical benefits relative to treatments used in current clinical practice.
Aims
To compare overall survival (OS) and time to next treatment (TTNT) in triple-class exposed patients with RRMM treated with cilta-cel vs. therapies as currently used in real world clinical practice (RWCP).
Methods
Individual patient data (IPD) for baseline risk factors and outcomes on OS/TTNT were available for cilta-cel patients from CARTITUDE-1 (September 2020) and for triple-class exposed RRMM patients treated with RWCP therapies from a German registry (OIs). This registry includes around 3,400 RRMM patients captured from a representative sample of 108 centers collected between January 2016 and March 2020. Patients with ECOG score 0 or 1 and ≥ 3 prior therapy lines, who received at least 1 subsequent active MM therapy after becoming triple-class exposed were selected from the registry. Hazard ratios (HR) with 95% confidence intervals (CI) for cilta-cel vs. RWCP were estimated for OS and TTNT using IPW weighted (Li et al., FJAjoe, 2019; Austin et al., PCJSim, 2016) and multivariable Cox proportional hazards regression models, adjusting for differences in commonly available baseline characteristics. Patients with multiple treatment lines initiated after fulfilling the inclusion criteria, contributed multiple times to the analyses, with line of therapy and its follow-up (observations) as unit of analysis and baseline information defined specific at initiation of each treatment line. Correlation of observations within patients was corrected using robust standard errors.
Results
Patients enrolled in CARTITUDE-1 (113 patients) and observations from RWCP (258 observations from 192 patients) were used for comparison. Cilta-cel patients had more advanced disease in terms of higher refractoriness, shorter time to progression on most recent prior line, higher number of prior lines, and shorter average duration of prior lines. RWCP included more patients with R-ISS stage III and ECOG score 1. Overlap weights analyses led to well-balanced cohorts and HR estimates for OS (HR 0.18, 95% CI 0.09-0.38) and TTNT (HR 0.19, 95% CI 0.09-0.39) were statistically significant in favor of cilta-cel. Multivariable regression analyses including baseline characteristics as covariates showed similar results confirming findings using IPW.
Conclusion
Comparative analyses using PLD, adjusting for differences in patient characteristics between both cohorts, shows that cilta-cel patients had significantly longer OS and TTNT compared to patients treated with therapies used in current clinical practice in Germany. These findings highlight cilta-cel’s potential as an effective treatment option to address currently unmet treatment needs in triple-class exposed patients with RRMM.
Keyword(s): CAR-T, Multiple myeloma
Abstract: EP972
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Patients with relapsed/refractory multiple myeloma (RRMM) who are triple-class exposed to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs) and anti-CD38 monoclonal antibodies (MoABs) have few treatment options available and poor outcomes (Gandhi et al., Leukemia, 2019). Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell (CAR-T) therapy, is studied in CARTITUDE-1, an open-label, single arm phase 1b/2 clinical trial assessing safety and efficacy of cilta-cel in adult patients with triple-class exposed RRMM. In absence of a comparator arm in CARTITUDE-1, comparison of trial outcomes versus an external cohort of similar patients allows to quantify clinical benefits relative to treatments used in current clinical practice.
Aims
To compare overall survival (OS) and time to next treatment (TTNT) in triple-class exposed patients with RRMM treated with cilta-cel vs. therapies as currently used in real world clinical practice (RWCP).
Methods
Individual patient data (IPD) for baseline risk factors and outcomes on OS/TTNT were available for cilta-cel patients from CARTITUDE-1 (September 2020) and for triple-class exposed RRMM patients treated with RWCP therapies from a German registry (OIs). This registry includes around 3,400 RRMM patients captured from a representative sample of 108 centers collected between January 2016 and March 2020. Patients with ECOG score 0 or 1 and ≥ 3 prior therapy lines, who received at least 1 subsequent active MM therapy after becoming triple-class exposed were selected from the registry. Hazard ratios (HR) with 95% confidence intervals (CI) for cilta-cel vs. RWCP were estimated for OS and TTNT using IPW weighted (Li et al., FJAjoe, 2019; Austin et al., PCJSim, 2016) and multivariable Cox proportional hazards regression models, adjusting for differences in commonly available baseline characteristics. Patients with multiple treatment lines initiated after fulfilling the inclusion criteria, contributed multiple times to the analyses, with line of therapy and its follow-up (observations) as unit of analysis and baseline information defined specific at initiation of each treatment line. Correlation of observations within patients was corrected using robust standard errors.
Results
Patients enrolled in CARTITUDE-1 (113 patients) and observations from RWCP (258 observations from 192 patients) were used for comparison. Cilta-cel patients had more advanced disease in terms of higher refractoriness, shorter time to progression on most recent prior line, higher number of prior lines, and shorter average duration of prior lines. RWCP included more patients with R-ISS stage III and ECOG score 1. Overlap weights analyses led to well-balanced cohorts and HR estimates for OS (HR 0.18, 95% CI 0.09-0.38) and TTNT (HR 0.19, 95% CI 0.09-0.39) were statistically significant in favor of cilta-cel. Multivariable regression analyses including baseline characteristics as covariates showed similar results confirming findings using IPW.
Conclusion
Comparative analyses using PLD, adjusting for differences in patient characteristics between both cohorts, shows that cilta-cel patients had significantly longer OS and TTNT compared to patients treated with therapies used in current clinical practice in Germany. These findings highlight cilta-cel’s potential as an effective treatment option to address currently unmet treatment needs in triple-class exposed patients with RRMM.
Keyword(s): CAR-T, Multiple myeloma