Beneficial initial HDT consolidation in myeloma with high-risk cytogenetics

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Patients with multiple myeloma and high-risk cytogenetics may benefit from treatment with high-dose consolidation rather than delaying this approach.

Although the overall survival (OS) benefit of high-dose therapy (HDT) depends on cytogenetics, the researchers recommend that patients with high-risk multiple myeloma receive this therapy initially as consolidation therapy. , according to the results published in Cancer.

After a median follow-up ranging from 3.1 to 7.8 years, researchers reported a pooled OS hazard ratio of 0.90 (95% CI, 0.70-1.17) for HDT compared to 0.66 (95% CI, 0.45-0.97) for standard-dose treatment (SDT) consolidation in people with standard-risk and high-risk disease. Additionally, when evaluating the effectiveness of SG with HDT between standard-risk and high-risk populations, researchers reported that the high-risk group benefited the most from the diet (P = .03). Additionally, the hazard ratios for progression-free survival (PFS) for HDT vs SDT in both cohorts were 0.65 (95% CI, 0.56-0.76) and 0.52 (95 %, 0.330.83), respectively, with a non-significant difference in HDT use in all risk groups (P = 0.25).

“Initial HDT consolidation, compared to SDT, continues to provide PFS benefits in newly diagnosed myeloma, with the magnitude of benefit being similar across all cytogenetic risk subgroups. However, the OS benefit of the initial HDT comes mainly from patients at high cytogenetic risk despite a high rate of salvage HDT in the control arms. Based on our results, HDT consolidation should not be delayed in patients at high cytogenetic risk outside of well-designed clinical trials. Future [randomized controlled trials] in high-risk transplant-eligible patients who are investigating novel initial immunotherapies such as CAR T cell therapy or T cell engagers should ensure that healthy patients in the control group are not deprived of initial HDT,” wrote writes the researchers.

To perform the systemic review and meta-analysis, researchers searched databases from 2000 to 2021. The main objective was to examine any differences in effectiveness between standard and high risk patients. risk treated with HDT. A total of 3305 citations were identified, of which 42 met the inclusion criteria. Of these trials, 6 were randomized controlled trials with a total of 2959 patients.

Among trial populations, 70.3% to 91.7% of patients were evaluable for cytogenetic risk stratification. Patients with high-risk cytogenetics represented 17% to 34% and 17% to 29% of those in the HDT and SDT treatment arms, respectively.

Induction regimens in the HDT arm included bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd; n=1); carfilzomib (Kyprolis), lenalidomide and dexamethasone (KRd; n=1); Rd (n=2); bortezomib, cyclophosphamide and dexamethasone (n=1); and carfilzomib, cyclophosphamide, and dexamethasone (KCd; n=1). Additionally, in the SDT arm, consolidation patterns included VRd (n=1); bortezomib, melphalan and prednisone (n=1); cyclophosphamide, lenalidomide, and dexamethasone (n=1); melphalan, prednisone, and lenalidomide (n=1); KRd (n=1); and KCd (n=1).

Patients who received HDT salvage treatment at relapse represented 43% to 77% of those included. In another approach to subgroup analysis, researchers reported a hazard ratio of 0.76 (95% CI, 0.54-1.08) for OS in high-risk populations compared to to standard-risk populations, respectively.

“This is the first systematic review and meta-analysis of consolidation outcomes with baseline HDT vs SDT by cytogenetic risk subgroup in newly diagnosed myeloma. We demonstrated that the magnitude of benefit of PFS with HDT consolidation versus SDT was similar in all cytogenetic risk subgroups, however, the benefit of OS with initial HDT consolidation was observed only in patients at high cytogenetic risk. the benefit of SG in high-risk patients was observed despite a high incidence of salvage grafts in the SDT group,” the researchers concluded.

Reference

Chakraborty R, Siddiqi R, Wilson G, et al. Impact of autologous transplantation on survival in newly diagnosed patients with multiple myeloma with high-risk cytogenetics: a meta-analysis of randomized controlled trials. Cancer. Published online April 4, 2022. doi:10.1002/cncr.34211

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