Meletios Athanasios Dimopoulos1, Jonathan L Kaufman2, Darrell White3, Gordon Cook4, Maria Rizzo5, Yingxin Xu6, Kyle Fahrbach6, Maren Gaudig7, Mary Slavcev8, Lindsay Dearden8, Annette Lam8. 1. National and Kapodistrian University of Athens, Athens, Greece. Electronic address: mdimop@cc.uoa.gr. 2. Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA. 3. Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada. 4. St James's Institute of Oncology, Leeds Teaching Hospitals National Health Services Trust and University of Leeds, Leeds, United Kingdom. 5. Evidera, London, United Kingdom. 6. Evidera, Waltham, MA. 7. Janssen-Cilag, Johnson & Johnson, Neuss, Germany. 8. Janssen Global Services, Raritan, NJ.
Abstract
BACKGROUND: Previous network meta-analyses combined studies of immunomodulatory drug (IMiD)-containing and IMiD-free regimens, despite a lack of head-to-head randomized controlled trials to robustly link them. However, patients with relapsed or refractory multiple myeloma (RRMM) treated with IMiD-containing regimens differ from those treated with IMiD-free regimens, especially relating to treatment history, which is an important treatment-effect modifier requiring clinical consideration when evaluating the most appropriate subsequent treatment options. A need exists to separately assess the efficacy of treatment regimens for patients who are suitable candidates for IMiD-containing and IMiD-free regimens. The presented analyses will enable clinicians to assess the best regimens to use in patients suitable for IMiD-containing regimens. MATERIALS AND METHODS: We used a Bayesian network meta-analysis to compare IMiD-containing regimens in patients with RRMM. Additionally, subgroup analyses were conducted stratified by previous therapy line, previous bortezomib therapy, and previous lenalidomide therapy. RESULTS: The results indicated that triplet combinations are more effective than doublet combinations. Of the triplet combinations, daratumumab, lenalidomide, dexamethasone (DRd) was significantly better in improving progression-free survival in patients with RRMM than were other IMiD-containing regimens (lenalidomide, dexamethasone [Rd]: hazard ratio [HR], 0.37; carfilzomib, Rd: HR, 0.54; elotuzumab, Rd: HR, 0.54; ixazomib, Rd: HR, 0.50). Similar trends were observed for overall survival and overall response. DRd showed the greatest probability of being the best treatment for all clinical efficacy outcomes. The subgroup analyses results were consistent with the base-case results. CONCLUSION: In patients with RRMM who are suitable for an IMiD-containing regimen, DRd showed clear advantages in survival and response outcomes compared with other IMiD-containing regimens.
BACKGROUND: Previous network meta-analyses combined studies of immunomodulatory drug (IMiD)-containing and IMiD-free regimens, despite a lack of head-to-head randomized controlled trials to robustly link them. However, patients with relapsed or refractory multiple myeloma (RRMM) treated with IMiD-containing regimens differ from those treated with IMiD-free regimens, especially relating to treatment history, which is an important treatment-effect modifier requiring clinical consideration when evaluating the most appropriate subsequent treatment options. A need exists to separately assess the efficacy of treatment regimens for patients who are suitable candidates for IMiD-containing and IMiD-free regimens. The presented analyses will enable clinicians to assess the best regimens to use in patients suitable for IMiD-containing regimens. MATERIALS AND METHODS: We used a Bayesian network meta-analysis to compare IMiD-containing regimens in patients with RRMM. Additionally, subgroup analyses were conducted stratified by previous therapy line, previous bortezomib therapy, and previous lenalidomide therapy. RESULTS: The results indicated that triplet combinations are more effective than doublet combinations. Of the triplet combinations, daratumumab, lenalidomide, dexamethasone (DRd) was significantly better in improving progression-free survival in patients with RRMM than were other IMiD-containing regimens (lenalidomide, dexamethasone [Rd]: hazard ratio [HR], 0.37; carfilzomib, Rd: HR, 0.54; elotuzumab, Rd: HR, 0.54; ixazomib, Rd: HR, 0.50). Similar trends were observed for overall survival and overall response. DRd showed the greatest probability of being the best treatment for all clinical efficacy outcomes. The subgroup analyses results were consistent with the base-case results. CONCLUSION: In patients with RRMM who are suitable for an IMiD-containing regimen, DRd showed clear advantages in survival and response outcomes compared with other IMiD-containing regimens.
Authors: Sergio Giralt; Luciano J Costa; David Maloney; Amrita Krishnan; Mingwei Fei; Joseph H Antin; Claudio Brunstein; Nancy Geller; Stacey Goodman; Parameswaran Hari; Brent Logan; Robert Lowsky; Muzaffar H Qazilbash; Firoozeh Sahebi; George Somlo; Scott Rowley; Dan T Vogl; David H Vesole; Marcelo Pasquini; Edward Stadtmauer Journal: Biol Blood Marrow Transplant Date: 2019-11-19 Impact factor: 5.742
Authors: Gergely Varga; Zsolt Nagy; Judit Demeter; Szabolcs Kosztolányi; Árpád Szomor; Hussain Alizadeh; Beáta Deák; Tamás Schneider; Márk Plander; Tamás Szendrei; László Váróczy; Árpád Illés; Árpád Bátai; Mónika Pető; Gábor Mikala Journal: Pathol Oncol Res Date: 2019-02-02 Impact factor: 3.201