https://orcid.org/0000-0003-2638-5773
Key Points
Simultaneous criteria allow for identifying patients with true progressive disease without overestimating the progression rate of myeloma.
Confirmatory results of progression in patients already having 2 biomarkers meeting criteria of progression at the same time is useless.
Disease response and progression assessment in multiple myeloma is based on various measurements of monoclonal protein (serum and urine protein electrophoresis, serum free light chain, and/or quantitative immunoglobulins). Currently, the International Myeloma Working Group consensus response criteria require 2 sequential assessments of any 1 marker made at any time before confirmation of disease progression and the institution of any new therapy. However, this can be cumbersome in clinical trials. Herein, we hypothesized that if 2 markers meet the progression criteria simultaneously, a repeat of either will not be necessary for confirmation. We retrospectively studied all sequential patients with myeloma enrolled in clinical trials at Mayo Clinic. We identified 583 episodes of confirmed progression in our study. Among the 583 progression episodes, nearly 70% (sensitivity of the simultaneous criteria) met the 2 simultaneous variable criteria at the first testing, indicating progression. Conversely, among 413 patients who met progression criteria by 2 simultaneous values, 98% (specificity of the simultaneous criteria) of patients subsequently had confirmed progression by sequential values. In summary, for patients with 2 disease burden markers meeting the simultaneous progression criteria, sequential assessment of either 1 for confirmation may not be necessary to determine disease progression.
Comments
Single assessment may be sufficient for both efficacy and progression evaluation in multiple myeloma
We agree with this conclusion and would like to highlight that our previous study, JCOG1105S1, provided complementary evidence focusing on efficacy evaluation3. In a supplementary analysis of our randomized phase II trial (JCOG1105, jRCTs031180097) 4,5, we showed that a single response assessment produced highly concordant results with the IMWG two-consecutive assessment criteria (κ = 0.76), with no disadvantage in predicting progression-free or overall survival. These results indicate that single assessment can be sufficient not only for PD determination but also for efficacy evaluation.
Taken together, these findings suggest that the long-standing IMWG requirement for two consecutive assessments may warrant reconsideration. Both for progression and efficacy, simplified criteria could better reflect real-world practice, minimize underestimation of responses, and may help guide the future refinement of response assessment in multiple myeloma.
References
1. Claveau J-S, Kapoor P, Binder M, et al. Eliminating the need for sequential confirmation of response in multiple myeloma. Blood. 2025;146(7):802–805.
2. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328–e346.
3. Nakamura N, Maruyama D, Machida R, et al. Single response assessment of transplant-ineligible multiple myeloma: a supplementary analysis of JCOG1105 (JCOG1105S1). Jpn. J. Clin. Oncol. 2021;51(7):1059–1066.
4. Maruyama D, Iida S, Ogawa G, et al. Randomised phase II study to optimise melphalan, prednisolone, and bortezomib in untreated multiple myeloma (JCOG1105). Br. J. Haematol. 2021;192(3):531–541.
5. Maruyama D, Iida S, Machida R, et al. Final analysis of randomized phase II study optimizing melphalan, prednisolone, bortezomib in multiple myeloma (JCOG1105). Cancer Sci. 2022;113(9):3267–3270.