Dear Editor,

Gain/amplification of 1q21 (1q21 +), chromosomal abnormalities frequently observed in patients with multiple myeloma (MM), are poor prognostic factors, with a weight of 0.5 points assigned to 1q21 + in the R2-ISS score [1, 2]. Daratumumab is an anti-CD38 monoclonal antibody effective in patients with newly diagnosed (ND) or relapsed/refractory (RR) MM. Good responses have been achieved even in patients with high-risk chromosomal abnormalities (HRCAs) [3]. However, 1q21 + impact on the effectiveness of daratumumab, lenalidomide, and dexamethasone (DRd), recommended as first-line treatment for patients with transplant-ineligible NDMM, remains controversial.

This retrospective, non-interventional cohort study compiled data from electronic medical records of 39 patients with MM who received DRd as first-line treatment from December 2019 to December 2023 at the Japanese Red Cross Medical Center (JRCMC). The study was approved by the JRCMC Institutional Review Board (details in the Ethics statement).

HRCAs were defined as the presence of t(4;14), t(14;16), or 17p deletion. 1q21 + was defined as a gain of 1q21 [gain(1q21), three copies] and amplification of 1q21 [amp(1q21), four or more copies]. Overall survival (OS) was defined as the interval between the first day of DRd treatment and death from any cause or the last follow-up. Progression-free survival (PFS) was defined as the interval between the first day of DRd treatment and the day of disease progression or death from any cause. Data were censored for patients who were alive or without disease progression at their last follow-up. The data cut-off was set to December 31, 2023. Survival rates were calculated using the Kaplan–Meier method and compared between groups using the log-rank test. P values < 0.05 were considered statistically significant. EZR software (https://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html) was used for all the statistical analyses [4].

Median age was 73 (range, 51–82) years, 20 (51.3%) were female, R-ISS was stage I, II, and III in 5 (12.8%), 28 (71.8%) and 6 (15.4%) patients respectively. HRCA was present in five (12.8%) patients and four (10.3%) had del(17p). 1q21 + was present in 13 (28.3%) patients; gain(1q21) in six, and amp(1q21) in seven, respectively. 1q21 + and HRCA were present simultaneously in only one case. No patients had extramedullary disease, but 17 patients had cardiac amyloidosis. There were no differences in patient backgrounds between groups according to with or without of 1q21 + , including cardiac amyloidosis and HRCA. Median follow-up was 15.6 (range, 0.3–48.3) months. Overall median PFS and OS were not reached and 3-year PFS and OS were 66.7% and 76.7%, respectively (Fig. 1A, B); 1- and 3-year PFS in patients with 1q21 + was 67.8% and 62.9%, and in those without 1q21 + was 62.9% and 62.9%, respectively, which were not significantly different (P = 0.77) (Fig. 1C). Additionally, 1- and 3-year OS in patients with 1q21 + were both 78.9% and in those without 1q21 + were 83.9% and 73.4%, respectively, and not significantly different (P = 0.82) (Fig. 1D). No significant differences in PFS and OS between patients with gain(1q21 +) and amp(1q21 +) (P = 0.95 and 0.84, respectively). HRCA had no impact on PFS and OS (P = 0.85 and 0.83, respectively). In contrast, patients with R-ISS III demonstrated significantly worse median PFS and OS compared to those with R-ISS I and II, with 6.0 and 0.9 months, respectively (P = 0.015 and 0.023, respectively).

Fig. 1
figure 1

Kaplan–Meier survival curves for progression-free and overall survival from the time of DRd initiation. PFS (A) and OS (B) of all patients. PFS stratified by 1q21 + (C) and OS stratified according to 1q21 + (D). OS, overall survival; PFS, progression-free survival; 1q21 + , gain/amplification of 1q21

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In this study, 1q21 + did not significant impact the outcomes of DRd therapy in patients with NDMM, consistence with previous reports [5]. In patients with RRMM, 1q21 + is a poor prognostic factor for daratumumab-based therapy [5,6,7]. Therefore, the impact of 1q21 + may differ between patients with NDMM and those with RRMM. In patients with NDMM, the impact of 1q copy number on prognosis has been reported, and our findings were contradictory to these reports [8]. This discrepancy may be due to the small sample size in our study, and further large-scale analyses are needed. The limitation of this study was its small, retrospective, and single-center design. Large-scale results could further strengthen this evidence. 1q21 + may have no negative impact on DRd therapy in patients with NDMM, supporting the recommendation of DRd therapy as first-line treatment.