patient care perspectives
All-Oral Treatment Strategies for Multiple Myeloma
Lenalidomide-based triplet therapy is standard in the treatment of multiple myeloma. An all-oral triplet, with ixazomib instead of bortezomib, may be an option for patients who cannot make once-weekly visits for their treatment.
Edward W. and Betty Knight Scripps Professor of Medicine
“IRd is an all-oral triplet, and this regimen may be considered when the reason for not reaching for the triplet is that the patient cannot travel to the clinic every week or is too frail to come in.”
With respect to oral doublet therapy for multiple myeloma, we are essentially referring to Rd (lenalidomide plus dexamethasone); however, we now know that we can add bortezomib even in frail patients without substantially increasing the toxicity by decreasing the dose of lenalidomide (ie, VRd-lite). In patients with newly diagnosed multiple myeloma, the addition of bortezomib to lenalidomide and dexamethasone has been shown to significantly improve progression-free and overall survivals. DRd (daratumumab plus lenalidomide and dexamethasone) is another regimen that can be used in the newly diagnosed transplant-ineligible population, and it also offers benefits over Rd alone. Thus, from the perspective of patient care, the value of triplet therapy should be emphasized.
However, both VRd-lite and DRd do require once-weekly visits. IRd (ixazomib plus lenalidomide and dexamethasone) is an all-oral triplet, and this regimen may be considered when the reason for not reaching for the triplet is that the patient cannot travel to the clinic every week or is too frail to come in. Data from placebo-controlled randomized trials show that this triplet is effective, adding to the progression-free survival. IRd is also well tolerated, with very limited toxicity, because ixazomib is extremely well tolerated.
Now, if a doublet is to be used in a newly diagnosed patient, the data comparing doublets (eg, Rd vs bortezomib plus dexamethasone) are challenging to interpret. High-quality comparative data are lacking. In the newly diagnosed setting, if you had to use only a doublet, I would use Rd. I believe that the data for Rd are much stronger than the data for bortezomib-dexamethasone. Rd has been used as a control arm in numerous clinical trials of newly diagnosed multiple myeloma, and the experience with Rd has been strong. This is all well settled. The bortezomib-dexamethasone data are coming mainly from 1 or 2 European trials. One of them was actually in a transplant-eligible patient population.
Barth P, Giri S, Reagan JL, Olszewski AJ. Outcomes of lenalidomide- or bortezomib-based regimens in older patients with plasma cell myeloma. Am J Hematol. 2021;96(1):14-22. doi:10.1002/ajh.25996
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. doi:10.1016/S0140-6736(16)31594-X
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. doi:10.1056/NEJMoa1817249
Facon T, Venner CP, Bahils N, et al. The phase 3 TOURMALINE-MM2 trial: oral ixazomib, lenalidomide, and dexamethasone (IRd) vs placebo-Rd for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) [abstract 551]. Abstract presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020.
Kumar SK, Berdeja JG, Niesvizky R, et al. Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance. Leukemia. 2019;33(7):1736-1746. doi:10.1038/s41375-019-0384-1