Contributions
Abstract: 89
Type: Scientific Session
Abstract Category: Therapy - Risk management for disease modifying treatments
Background: As more effective disease-modifying therapies (DMTs) can be expected to exert more profound effects on the immune system, increased cancer risk is a potential long-term concern. Despite this, long-term follow-up data of cancer risks in large real-world cohorts of multiple sclerosis (MS) patients treated with novel DMTs is still limited. This potential risk was underscored in the ORATORIO trial program for ocrelizumab, a novel anti-CD20 MS DMT, where an imbalance in the number of detected breast cancers was seen between the active treatment and comparator arms (26.1 vs 0 cancers / 10 000 person years) [Montalban et al. N Engl J Med 2017].
Objective: To i) determine the risk of breast cancer in female MS patients treated with RTX and ii) compare the risk of all types of cancer in MS patients treated with rituximab (RTX), fingolimod (FGL), and natalizumab (NTZ).
Methods: We performed a nationwide register-based cohort study of MS patients treated between 2006-2016, based on data from the Swedish MS register and linkage to national health care and census registers. Incidence rate of breast cancer was calculated among female patients on RTX. Hazard ratios (HR) and 95% confidence intervals (CI) for all types of cancer were estimated using multivariable Cox regression with robust standard errors. Baseline characteristics were adjusted for using propensity scores (PS) calculated by multinomial logistic regression, including: demographic factors, MS-related disability, and medical history including previous cancer.
Results: In the cohort of female patients on RTX, we identified 2 386 therapy starts and 3 breast cancers over 4 872 person years, corresponding to an incidence rate of 6.2 cancers / 10 000 person years (95% CI: 1.3-18.0). In the cohort of all patients, we identified a total of 8 064 therapy starts and 172 cancers of any type over 28 648 person years. PS-adjusted HR were 2.1 (95% CI: 1.3-3.6) for FGL and 1.9 (95% CI: 1.0-3.4) for NTZ, compared to RTX.
Conclusions: We found an IR for breast cancer on RTX comparable to that of the general female population and lower than the IR reported in the ocrelizumab pivotal trial. For cancer of any type, no increased risk could be seen for RTX, compared to FGL and NTZ, and possibly even a lower rate. Although these preliminary results thus indicate that cancer might not be a major concern when treating MS patients with RTX relative to other DMTs, more detailed analyses are necessary before final conclusions.
Disclosure: PA and TF report no conflicts of interest. FP has received research grants from Biogen, Novartis, and Genzyme, and fees for serving as Chair of DMC in clinical trials with Parexel.
Abstract: 89
Type: Scientific Session
Abstract Category: Therapy - Risk management for disease modifying treatments
Background: As more effective disease-modifying therapies (DMTs) can be expected to exert more profound effects on the immune system, increased cancer risk is a potential long-term concern. Despite this, long-term follow-up data of cancer risks in large real-world cohorts of multiple sclerosis (MS) patients treated with novel DMTs is still limited. This potential risk was underscored in the ORATORIO trial program for ocrelizumab, a novel anti-CD20 MS DMT, where an imbalance in the number of detected breast cancers was seen between the active treatment and comparator arms (26.1 vs 0 cancers / 10 000 person years) [Montalban et al. N Engl J Med 2017].
Objective: To i) determine the risk of breast cancer in female MS patients treated with RTX and ii) compare the risk of all types of cancer in MS patients treated with rituximab (RTX), fingolimod (FGL), and natalizumab (NTZ).
Methods: We performed a nationwide register-based cohort study of MS patients treated between 2006-2016, based on data from the Swedish MS register and linkage to national health care and census registers. Incidence rate of breast cancer was calculated among female patients on RTX. Hazard ratios (HR) and 95% confidence intervals (CI) for all types of cancer were estimated using multivariable Cox regression with robust standard errors. Baseline characteristics were adjusted for using propensity scores (PS) calculated by multinomial logistic regression, including: demographic factors, MS-related disability, and medical history including previous cancer.
Results: In the cohort of female patients on RTX, we identified 2 386 therapy starts and 3 breast cancers over 4 872 person years, corresponding to an incidence rate of 6.2 cancers / 10 000 person years (95% CI: 1.3-18.0). In the cohort of all patients, we identified a total of 8 064 therapy starts and 172 cancers of any type over 28 648 person years. PS-adjusted HR were 2.1 (95% CI: 1.3-3.6) for FGL and 1.9 (95% CI: 1.0-3.4) for NTZ, compared to RTX.
Conclusions: We found an IR for breast cancer on RTX comparable to that of the general female population and lower than the IR reported in the ocrelizumab pivotal trial. For cancer of any type, no increased risk could be seen for RTX, compared to FGL and NTZ, and possibly even a lower rate. Although these preliminary results thus indicate that cancer might not be a major concern when treating MS patients with RTX relative to other DMTs, more detailed analyses are necessary before final conclusions.
Disclosure: PA and TF report no conflicts of interest. FP has received research grants from Biogen, Novartis, and Genzyme, and fees for serving as Chair of DMC in clinical trials with Parexel.