Contributions
Abstract: P1878
Type: Poster
Abstract Category: Late breaking news
Background: An independent meta-analysis (Pakpoor et al. Neurol Neuroimmunol Neuroinflamm 2015;2:e158) assessed malignancy risk in Phase III trials (with a 2-year duration) of disease modifying drugs (DMDs) in patients with relapsing MS (RMS). This found no increased rate of malignancy with cladribine tablets (CT) compared with other DMD treatment groups, but an unusually low rate was observed in the placebo group. Lymphocyte reductions occur following annual courses of CT, but are transient relative to the sustained clinical efficacy characteristic of selective immune reconstitution therapy. Data from additional trials involving treatment with CT 3.5 mg/kg (CT3.5) and a safety registry (up to 8 years of follow up) are now available, allowing further insights into malignancy risk.
Objective: To assess malignancy risk with CT3.5 monotherapy and placebo (PBO) in data from 3 Phase III trials and the PREMIERE registry, and to compare the incidence rate with a global malignancy database.
Methods: The CT 3.5 population comprised 923 patients (3433 patient-years' [PY] total exposure time) and the PBO group comprised 641 patients (2026 PY). Individual case reports of malignancies were reviewed by an independent, blinded adjudication committee. Standardized incidence ratios (SIR) for malignancies were calculated in relation to the GLOBOCAN reference population (excluding non-melanoma skin cancers [NMSCs]) and a Danish reference population to compare NMSC rates.
Results: The incidence per 100 PY of confirmed malignancy was 0.293 (95%CI 0.158-0.544) for CT3.5 and 0.148 (95%CI 0.048-0.460) for PBO; the 95% CI (-0.166-0.414) of the risk difference included 0. Analysis of the malignancy SIR showed that the rate of malignancies with CT 3.5 was almost identical (0.97, 95%CI 0.44-1.85) to the GLOBOCAN matched reference population. The SIR for the PBO group was numerically lower (0.48, 95% CI 0.14-1.53). There were no cases of haematological, lymphoproliferative or virus-induced cancers. There was no clustering of specific tumour types, and the incidence of skin cancer was not increased after treatment with CT3.5 compared with PBO. The incidence of malignancies with CT3.5 was constant and did not increase over time.
Conclusions: Analysis of malignancy rates in a cohort that includes patients with up to 8 years of follow up confirms the conclusions of the earlier meta-analysis; the incidence of malignancies with CT3.5 is similar to that in a matched reference population.
Disclosure: This study was sponsored by EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
Author disclosures:
Andrew Galazka: is an employee of Merck, Aubonne, Switzerland, a division of Merck KGaA, Darmstadt, Germany.
Axel Nolting: is an employee of Merck KGaA, Darmstadt, Germany.
Stuart Cook: has received honoraria for lectures/consultations from Merck, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
Thomas Leist: has received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience.
Giancarlo Comi: has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, Receptos, Biogen Idec, Genentech-Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptos, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
Xavier Montalban: has received speaker honoraria and travel expenses for scientific meetings, steering committee member, and advisory board member of clinical trials for Bayer Schering Pharma, Biogen Idec, EMD Serono, Genentech, Genzyme, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
Christine Hicking: is an employee of Merck KGaA, Darmstadt, Germany.
Fernando Dangond: is an employee of EMD Serono, Inc., Billerica, United States, a business of Merck KGaA, Darmstadt, Germany.
Abstract: P1878
Type: Poster
Abstract Category: Late breaking news
Background: An independent meta-analysis (Pakpoor et al. Neurol Neuroimmunol Neuroinflamm 2015;2:e158) assessed malignancy risk in Phase III trials (with a 2-year duration) of disease modifying drugs (DMDs) in patients with relapsing MS (RMS). This found no increased rate of malignancy with cladribine tablets (CT) compared with other DMD treatment groups, but an unusually low rate was observed in the placebo group. Lymphocyte reductions occur following annual courses of CT, but are transient relative to the sustained clinical efficacy characteristic of selective immune reconstitution therapy. Data from additional trials involving treatment with CT 3.5 mg/kg (CT3.5) and a safety registry (up to 8 years of follow up) are now available, allowing further insights into malignancy risk.
Objective: To assess malignancy risk with CT3.5 monotherapy and placebo (PBO) in data from 3 Phase III trials and the PREMIERE registry, and to compare the incidence rate with a global malignancy database.
Methods: The CT 3.5 population comprised 923 patients (3433 patient-years' [PY] total exposure time) and the PBO group comprised 641 patients (2026 PY). Individual case reports of malignancies were reviewed by an independent, blinded adjudication committee. Standardized incidence ratios (SIR) for malignancies were calculated in relation to the GLOBOCAN reference population (excluding non-melanoma skin cancers [NMSCs]) and a Danish reference population to compare NMSC rates.
Results: The incidence per 100 PY of confirmed malignancy was 0.293 (95%CI 0.158-0.544) for CT3.5 and 0.148 (95%CI 0.048-0.460) for PBO; the 95% CI (-0.166-0.414) of the risk difference included 0. Analysis of the malignancy SIR showed that the rate of malignancies with CT 3.5 was almost identical (0.97, 95%CI 0.44-1.85) to the GLOBOCAN matched reference population. The SIR for the PBO group was numerically lower (0.48, 95% CI 0.14-1.53). There were no cases of haematological, lymphoproliferative or virus-induced cancers. There was no clustering of specific tumour types, and the incidence of skin cancer was not increased after treatment with CT3.5 compared with PBO. The incidence of malignancies with CT3.5 was constant and did not increase over time.
Conclusions: Analysis of malignancy rates in a cohort that includes patients with up to 8 years of follow up confirms the conclusions of the earlier meta-analysis; the incidence of malignancies with CT3.5 is similar to that in a matched reference population.
Disclosure: This study was sponsored by EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
Author disclosures:
Andrew Galazka: is an employee of Merck, Aubonne, Switzerland, a division of Merck KGaA, Darmstadt, Germany.
Axel Nolting: is an employee of Merck KGaA, Darmstadt, Germany.
Stuart Cook: has received honoraria for lectures/consultations from Merck, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
Thomas Leist: has received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience.
Giancarlo Comi: has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, Receptos, Biogen Idec, Genentech-Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptos, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
Xavier Montalban: has received speaker honoraria and travel expenses for scientific meetings, steering committee member, and advisory board member of clinical trials for Bayer Schering Pharma, Biogen Idec, EMD Serono, Genentech, Genzyme, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
Christine Hicking: is an employee of Merck KGaA, Darmstadt, Germany.
Fernando Dangond: is an employee of EMD Serono, Inc., Billerica, United States, a business of Merck KGaA, Darmstadt, Germany.