Min Kyoung Kim

Bortezomib-melphalan-prednisone (VMP) is an established induction regimen for transplant-ineligible newly diagnosed multiple myeloma (NDMM), yet optimal post-induction strategies remain unclear. This study evaluated the effectiveness of bortezomib maintenance following VMP using target trial emulation. We compared a prospective maintenance cohort (KMMWP-174 study) with an external control cohort from a multicenter registry. Eligible patients completed 9 VMP cycles, achieved ≥ partial response, and were progression-free for 60 days. The index date was maintenance initiation for cases and day 60 post-VMP for controls. Propensity score matching (1:1) balanced baseline covariates. The primary endpoint was progression-free survival (PFS); overall survival (OS) was secondary. Sensitivity analyses included multivariable regression, landmark analyses, and E-value assessment. Among 178 eligible patients, 60 comprised the maintenance cohort and 118 the control cohort; 54 per group were analyzed after matching. Median PFS was significantly longer with bortezomib maintenance (26.5 vs. 8.8 months; HR 0.437, 95% CI: 0.275–0.694, P < 0.001). PFS benefits were consistent across subgroups, including patients aged ≥ 70 years, those with ISS stage II-III disease, and those with high-risk cytogenetics. OS showed a favorable trend (HR 0.703, P = 0.252). Grade ≥ 3 adverse events occurred in 31.4% (control) and 18.7% (maintenance). No grade ≥ 3 peripheral neuropathy was observed. Bortezomib maintenance following VMP significantly prolonged PFS in transplant-ineligible NDMM with acceptable toxicity. These real-world data support proteasome inhibitor-based maintenance where VMP remains widely used, particularly among older adults with limited treatment options.

Lee SE, et al. J Korean Med Sci. 2024 Jan;39(3):e24. https://doi.org/10.3346/jkms.2024.39.e24

We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before (p = 0.260) and after (p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59–1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68–3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice.

Kim JS, et al. J Korean Med Sci. 2023 Sep;38:e328. https://doi.org/10.3346/jkms.2023.38.e328

External beam radiotherapy is effective for stage I orbital mucosa-associated lymphoid tissue lymphoma (MALToma). Hence, very-low-dose radiotherapy is increasingly being investigated. We conducted a single-center prospective phase II trial to evaluate the effectiveness of very-low-dose radiotherapy of 4 Gy (2 Gy × 2 fractions) in pathologically confirmed stage I orbital MALToma. In this first prospective trial, patients with complete response were observed after 3–6 months of follow-up. For patients without complete remission, a radiation dose of 24 Gy/12 fractions was additionally delivered. The primary endpoint was complete response rate; secondary endpoints were overall survival, local control, and progression-free survival. Seventeen patients were screened and three patients refused enrollment during October 2018–October 2021. Thus, 14 patients (17 eyes) were analyzed (median follow-up, 28.2 months). The overall response rate was 100% (complete remission: 11 lesions; partial remission: six lesions). In all lesions with residual disease, additional radiation therapy (dose: 24 Gy) was performed. One local failure was observed. Therefore, 4 Gy ultralow-dose radiation therapy for orbital MALToma was safely performed with a planned second-line treatment in patients without complete remission. This is the first prospective study to report the effectiveness of ultralow-dose radiotherapy of 4 Gy for stage I orbital MALToma treatment.

Compared to ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) patients with symptoms related invasion beyond the ocular adnexa, the different approaches to staging assessment may be required in OAML patients with symptoms limited to the ocular adnexa. Seventy-six patients to be diagnosed with OAML and performed bone marrow biopsy and imaging study at Yeungnam University Hospital in 1995–2014 were enrolled. Patients with symptoms limited to the ocular adnexa were included. Computed tomography, magnetic resonance imaging, positron emission tomography (PET), and bone marrow biopsies were performed for diagnosis, NM staging and follow up evaluation. Most patients were treated with external beam irradiation (median dose, 30 Gray (Gy)). The relapse-free survival (RFS) was analyzed according to the tumor laterality and TNM stage. The median follow-up period was 72 months. The 5-year RFS and overall survival rates were 82.1% and 95.6% respectively. Of all 76 patients, lymph node and bone marrow involvement was identified in 1 patient, respectively. Among the 3 patients with T4 stage as tumor invasion beyond ocular adnexa, bone marrow involvement was confirmed in a patient with left cheek invasion. Only 11 of the 43 patients who underwent PET showed positive uptakes in orbital lesion. The patients with advanced stage were alive without recurrences. Bone marrow examination is useful in OAML patients with T4 for extended stage assessment. The AJCC TNM staging system was not significantly predictive factor for relapse, but may contribute to clarifying the patient group that needs bone marrow study.

Lee JM, et al. J Korean Med Sci. 2021 Jan;36(4):e37. https://doi.org/10.3346/jkms.2021.36.e37

Immune system dysfunction is associated with head and neck squamous cell carcinoma (HNSCC) development and progression and immune checkpoint inhibitors have demonstrated substantial survival benefits in platinum-refractory HNSCC; therefore, we examined the prognostic value of immune-related gene (IRG) expression in HNSCC. We analyzed the expression of 82 IRGs in 71 patients with HNSCC enrolled in a feasibility study for a prospective HNSCC biomarker-driven umbrella trial (Korean Cancer Study Group TRIUMPH study, NCT03292250). CD200R1 was identified as an independent prognostic factor and validated in GEO and TCGA database. CD2000R1 mRNA expression was found to be an independent favorable prognostic factor in patients with HNSCC. Moreover, CD200R1 was found to affect genes and pathways associated with the immune response, while seven differentially expressed genes (CD8A, DOK2, CX3CR1, TYROBP, CXCL9, CD300LF, IFNG) were associated with CD200R1 expression. Samples with higher CD200R1 expression displayed higher tumor-infiltrating immune cell counts both in silico and in histological analysis. These findings will help in the development of more accurate prognostic tools and suggest CD200R1 modulation as a HNSCC immunotherapy.

Lee JM, et al. J Korean Med Sci. 2020 Oct;35(46):e393. https://doi.org/10.3346/jkms.2020.35.e393