Median overall survival for patients with newly diagnosed multiple myeloma may surpass ten years. Nonetheless, many patients face considerable treatment-related morbidity and relapsed disease. Owing to this typically long overall survival, most multiple myeloma trials now use progression-free survival as their primary end point. In this Comment, we highlight circumstances in which this end point does not best answer the questions that various trials seek to investigate.
This is a preview of subscription content, access via your institution
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Mohyuddin, G. R. et al. Use of endpoints in multiple myeloma randomized controlled trials over the last 15 years: A systematic review. Am. J. Hematol. 96, 690–697 (2021).
Haslam, A. & Prasad, V. When is crossover desirable in cancer drug trials and when is it problematic? Ann. Oncol. 29, 1079–1081 (2018).
Schjesvold, F. H. et al. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Lancet Haematol. 9, e98–e110 (2022).
Kumar, S. K. et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 21, 1630–1642 (2020).
Rajkumar, S. V. et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 11, 29–37 (2010).
Gill, S. K. et al. Inferior outcomes of patients with quad and penta-refractory multiple myeloma (mm) compared to those of patients who have been quad and penta exposed. Blood 138, 4742–4742 (2021).
Gyawali, B. & Prasad, V. Combining drugs and extending treatment — a PFS end point is not sufficient. Nat. Rev. Clin. Oncol. 14, 521–522 (2017).
Mohyuddin, G. R., Koehn, K., Abdallah, A. O., Goodman, A. M. & Prasad, V. Reporting of postprotocol therapies and attrition in multiple myeloma randomized clinical trials: a systematic review. JAMA Netw. Open 4, e218084 (2021).
Munshi, N. C. et al. Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma: a meta-analysis. JAMA Oncol. 3, 28–35 (2017).
The authors declare no competing interests.
About this article
Cite this article
Cliff, E.R.S., Rehman Mohyuddin, G. Overall survival as a primary end point in multiple myeloma trials. Nat Rev Clin Oncol 19, 565–566 (2022). https://doi.org/10.1038/s41571-022-00665-7