Page 222 - Haematologica Vol. 109 - July 2024

ARTICLE - Carfilzomib, thalidomide and dexamethasone (KTd) in RRMM S. Ninkovic et al.
(Figure 2A). Combined, these observations suggest that carfilzomib ought to be used until disease progression, a strategy which was shown to be safe and effective in the ENDEAVOR study.14
Consistent with previous reports on pre-specified sub- group analyses, albeit acknowledging limited numbers of patients within these subgroups, the KTd combination ap- pears equally successful irrespective of age or cytogenetic risk group of the patients. Similarly, Revised International Staging System score, prior stem cell transplant or prior exposure to bortezomib or thalidomide did not have an impact on outcomes.20-22 Although 32% of patients had previously been treated with thalidomide, with exposure rates of 15% in the non-Asian and 50% in the Asian study cohorts, this disparity appears to align with regional front- line therapy practices at the time. It is important to note that data regarding refractoriness to prior treatments were not collected in this study, posing a minor limitation in in- terpreting the results of these sub-group analyses. A less favorable outcome compared to that of the overall group was still seen in patients with elevated b2-microglobulin with a trend towards increased efficacy of KTd in patients
having second- or third-line therapy, similarly consistent with evidence that carfilzomib remains efficacious whether used early or late in relapse.23 In our study, patients with poor renal function still did poorly compared to the overall cohort, and while the sample size is too small to make de- finitive remarks, impaired renal function is known to be a poor prognostic factor in myeloma.24 Strong evidence already exists that carfilzomib is safe and efficacious irrespective of renal function, with no starting dose adjustments required even in patients with end-stage renal failure.25,26 Given that thalidomide, as opposed to lenalidomide, is more practical in patients with renal impairment, KTd could be an effective combination when lenalidomide cannot be used.
Of interest, both the impressive overall response rate and the benefit to PFS were similarly observed in both the Asian and non-Asian cohorts of patients. This is consistent with previous reports of efficacy of carfilzomib in Asian patients and a subgroup analysis of the ENDEAVOR and A.R.R.O.W. trials which specifically reported on outcomes in Asian patients.27-29 This report, while cognizant of the smaller sample size, highlighted increased rates of ≥ grade 3 adverse events, especially grade ≥3 cardiac failure, in the Asian pop-
Figure 3. Hazard ratios and 95% confidence intervals for progression-free survival in pre-specified subgroups according to base- line characteristics. HR: hazard ratio; 95% CI: 95% confidence interval; yrs: years; FISH: fluorescence in situ hybridization; R-ISS: Revised International Staging System; PL: prior line; autoSCT: autologous stem cell transplant; eGFR: estimated glomerular fil- tration rate; TTP: thrombotic thrombocytopenic purpura.
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