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High-Risk Lesions: A Consistent Predictor of Ultra-High Risk Multiple Myeloma
Speaking at the 64th American Society of Hematology Annual Meeting and Exposition, Martin F Kaiser, MD, FRCP, FRCPath, presented “Co-occurrence of high-risk lesions is a consistent predictor of ultra-high risk multiple myeloma in newly diagnosed and relapsed/refractory patients: Meta-analysis of 5,808 trial patients.”
Results from a large-scale meta-analysis of randomized clinical trials by Dr Kaiser and colleagues support the assessment of and reporting on single hit/high risk and double hit/ultra-high risk patient groups in clinical trials, including trials for relapsed/refractory multiple myeloma (RRMM), as well as highlighting the importance of access to extended genetic profiling in routine patient care. “It’s also important for informed discussions with patients and general care,” Dr Kaiser added during his presentation. “It can be follow-up intervals, it can be prioritization of certain procedures you need to do in some groups and maybe not as quickly as in others.”
The researchers presented their findings based on the need for readily accessible and easy-to-implement risk prediction tools that allow application in clinical trials and standard care.
“Such a care requires validated, really reliable, clinically accessible tools. We want to have something we can use in the clinic,” Dr Kaiser stated.
The researchers identified 14 prospective randomized interventional trials with availability of extended genetic profiles, including complete information on risk markers gain(1q), t(4;14), del(17p), and consisted of 9 trials for newly diagnosed MM (NDMM) (4 including transplant eligible [TE], 3 transplant ineligible [TNE], 2 both) and 5 trials for RRMM. Cox proportional hazards models were performed for each trial for outcome analysis in relation to presence of no (no hit), one (single hit), or two or more (double hit) risk markers.
A total of 5,808 trial patients were included in the analysis, consisting of 4,807 patients with NDMM (3,296 transplant-eligible [TE], 1,511 transplant-ineligible [TNE]) as well as 1,001 patients with RRMM.
Frequencies for presence of single (median: 38%; range 32%-48%) or double hit (14%; 9%-22%) were found to be comparable between trials. Patients with double hit had a shorter overall survival (OS), meta-analysis summary hazard ratios (HR) for OS were 2.97 (95% CI: 2.37-3.71; P <.0001) for double hit vs 1.87 (95% CI: 1.60-2.19; P <.0001) for single hit. Summary HRs for progression-free survival (PFS) by meta-analysis were 2.18 (95% CI: 1.92-2.47; P <.0001) for double hit vs 1.63 (1.43-1.86; P <.0001) for single hit.
Results were consistent between NDMM and RRMM trials, and between trials with proteasome inhibitor-based (eg, GMMG-HD4/HOVON-65; MUKFive) and immunomodulatory drug (IMiD)-based regimens (eg, GMMG-MM5; MUKSeven). The association of double hit with shortened OS was most pronounced in trials with modern, intensive PI/IMiD induction/autologous stem cell transplantation/maintenance treatments concepts (eg, FORTE, GMMG-HD6, and NCRI Myeloma XI). HRs were lower in trials for older TNE patients; outcome was consistently the worst for patients with double hit MM.
“We feel, in clinical trials, especially as we enter a new era of new agents that are going into the clinic, this could really be valuable knowledge,” concluded Dr Kaiser.
Kaiser MF, Sonneveld P, Cairns D, et al. Co-Occurrence of High-Risk Lesions Is a Consistent Predictor of Ultra-High Risk Multiple Myeloma in Newly Diagnosed and Relapsed/Refractory Patients – Meta-Analysis of 5,808 Trial Patients. Presented at: 64th ASH Annual Meeting and Exposition; December 10-13, 2022. Abstract 644.
