Looking Ahead: 4‑Drug Combinations
Based on data from various trials, Dr Suzuki anticipates a shift toward the use of quadruplet treatment regimens. In the CASSIOPEIA trial (ClinicalTrials.gov Identifier: NCT02541383), for example, 39% of patients receiving daratumumab with bortezomib, thalidomide, and dexamethasone (Dara-VTd) achieved CR or better at 100 days post-ASCT, compared to 26% of those receiving VTd alone. In addition, 64% of those in the Dara-VTd group achieved MRD– compared to 44% in the VTd group (both P <.0001).5
Promising results from a trial of of Dara-VRd led to a phase 3 study in which patients “who achieve sustained MRD– for 12 months after ≥ 24 months of maintenance will stop Dara but continue Len maintenance until PD; upon loss of CR or MRD–, patients will restart Dara treatment,” Dr Suzuki explained. “The results of this study will address how MRD– guides treatment modification.”
For select patients with RRMM, he also noted the potential roles of chimeric antigen receptor‑T cell therapy targeting anti‑B‑cell maturation antigen, multiagent combination chemotherapy such as VTDPACE (Bor/Thal/Dex, cisplatin, doxorubicin, CPA, and etoposide), and allogeneic stem cell transplantation.
Dr Suzuki also emphasized the exorbitant cost of myeloma therapies, underscoring the need for more financially sustainable treatment models. “Ongoing efforts to improve the treatment paradigm even further include using oncogenomics to better characterize molecular pathogenesis and to develop refined patient stratification and personalized treatment of MM using immune-based therapies, including antibodies, cytokines, and novel immunocytic strategies,” he concluded.
Disclosure: Dr Suzuki has received honoraria from Celgene, Takeda, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie, and Janssen; consulted for Amgen, Janssen, Takeda, and Celgene; and received research funding from Bristol-Myers Squibb, Celgene, and Amgen.
- Suzuki K. Latest treatment strategies aiming for a cure in transplant-eligible multiple myeloma patients: how I cure younger MM patients with lower cost. Int J Hematol. 2020;111(4):512-518.
- Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-527.
- Usmani SZ, Hoering A, Cavo M, et al. Clinical predictors of long-term survival in newly diagnosed transplant eligible multiple myeloma – an IMWG Research Project. Blood Cancer J. 2018;8(12):123.
- Facon T, Kumar S, Plesner T, et al; MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019;380(22):2104-2115.
- Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29-38.