Vol 27, No 4 (2025)

Multiple myeloma (MM) is a clonal malignant lymphoproliferative disease with a continuously recurrent course. There has been a significant evolution of approaches to MM therapy, including the use of new induction regimens with not three, but four drugs with different mechanisms of action. This approach applies to patients both eligible and non-eligible for autologous hematopoietic stem cell transplantation (auto-HSCT). Thus, an international randomized clinical trial has shown the efficacy and safety of adding isatuximab (an anti-CD38 monoclonal antibody) to triplet therapy in patients with newly diagnosed MM. The publication presents two authors’ clinical cases of the use of the Isa-VRd induction regimen in patients with newly diagnosed MM. In a 61-year-old patient to undergo auto-HSCT (transplantation is not scheduled as initial therapy), after 4 induction cycles with Isa-VRd regimen, the combined positron-emission and X-ray computed tomography showed a pronounced decrease in the metabolic activity of tumor tissue, a negative status of minimal residual disease was achieved with the sensitivity of the NGF (next generation flow) method of 10⁻⁵; currently, maintenance therapy is ongoing. In a 63-year-old patient, a candidate for auto-HSCT, after completing 3 cycles of induction therapy with Isa-VRd quadruplet and an auto-HSCT, strict complete remission of the disease was achieved according to the International Myeloma Working Group (IMWG) 2016 criteria. Maintenance therapy is currently ongoing.

Triple-negative breast cancer (TNBC) is the most unfavorable subtype of breast cancer. Achieving pathological complete responce (pCR) is an important prognostic factor in patients diagnosed with TNBC, as it is associated with increased overall and disease-free survival. Currently, clinical parameters and pathological examination of resection tissue after surgery are used to evaluate the effectiveness of neoadjuvant drug chemotherapy (NAC). Traditional clinical and instrumental methods used in routine practice (examination, palpation, ultrasound of the mammary glands and regional areas, mammography, and MRI of the mammary glands) often do not allow for an accurate assessment of the treatment effect. The rate of detection of complete responses may be lower with clinical and instrumental assessment of the effect compared to pathological examination. In this regard, there is growing interest in assessing the effect of NAC based on changes in circulating tumor DNA (ctDNA) levels in the blood, which is characterized by the presence of genetic alterations specific to tumor tissue, i.e., liquid biopsy. This study examines two clinical cases of TNBC, determining the dynamics of ctDNA level changes during treatment and comparing these results with the severity of pathological tumor responce after NAC. In one case, pathological complete responce was achieved, while in the second, significant residual tumor was detected. Mutations for tracking ctDNA level dynamics were selected based on bioinformatics analysis of whole-exome sequencing of tumor biopsy samples and patient’s blood. Plasma ctDNA levels were assessed using digital PCR (dPCR). We obtained quantitative results for ctDNA determination in the plasma of patients with TNBC at five points and compared the dynamics of ctDNA level changes with the results of NAC. The study discusses the possible relationship between the observed ctDNA dynamics and treatment response (achievement of complete pathological tumor regression) and the feasibility of using liquid biopsy in predicting tumor response to NAC.

Background. Recent clinical trials have demonstrated the potential efficacy of immune checkpoint inhibitors as monotherapy or in combination for the treatment of patients with advanced cervical cancer (CC). At the same time, the effectiveness and safety of this treatment approach in domestic clinical practice remain largely unexplored.

Aim. To evaluate the efficacy and safety of immune checkpoint inhibitors in patients with advanced CC in real clinical practice.

Materials and methods. From January 2018 to June 2023, a retrospective analysis of the efficacy and safety of pembrolizumab therapy was performed in 96 patients, all with histologically confirmed CC: squamous cell (n=81), adenocarcinoma (n=12) and adenosquamous cancer (n=3). At the start of immunotherapy, 21.9% of patients had locoregional relapse and 78.1% distant metastases. The proportion of patients with de novo metastatic CC was 12.5%. The vast majority had a satisfactory somatic condition at the start of therapy – ECOG 0-1 (80.2%). The response to therapy was assessed according to the iRECIST criteria. Statistical analysis was performed using StatTech v. 4.8.11. Patient survival function was estimated using the Kaplan–Meier method.

Results. The objective response rate was 29.2% (n=28), disease control was achieved in 52.1% (n=50) of patients. The median time to response was 3.0 months (1.8–16.0 months), the median duration of response was 14.0 months (1.9–53.2 months). Median рrogression-free survival was 7.6 months (95% confidence interval – CI 5.0–11.0), the median overall survival was 24.0 months (95% CI 15.0–32.4). The median overall survival in the local recurrence group was 11.5 months (95% CI 3.4–22.2), in the group with metachronous metastases – 32.4 months (95% CI 21.4–72.2), and in the group with initially metastatic cancer – 7.8 months (95% CI 5.2–28.5).

Conclusion. Monotherapy with pembrolizumab has shown high efficacy and manageable safety in patients with advanced CC. However, these advantages are primarily observed in the group of patients with metachronous distant metastases. The presence of an unresected or unirradiated primary or recurrent tumor contributes to poorer outcomes with immunotherapy.

Aim. To identify mutational profile differences of non-muscle-invasive (NMIUC) and muscle-invasive urothelial carcinoma (MIUC) of the bladder, assessed through isolating alterations in deoxyribonucleic (DNA) and ribonucleic (RNA) acids by a next-generation sequencing (NGS) method using a panel of 523 genes.

Materials and methods. Tumor tissue and medical data of 72 patients with histologically confirmed bladder UC were studied. NMIUC was diagnosed in 40 (55.6%) patients, and MIUC in 32 (44.4%) patients. In 25 (34.7%) samples the tumor grade was assessed as low: 24 (33.3%) with NMIUC and 1 (1.4%) with MIUC, and in 47 (65.3%) as high: 16 (22.2%) with NMIUC, 31 (43.1%) with MIUC. In isolated tumor cells DNA and RNA alterations were detected by NGS using a panel of 523 genes.

Results. NMIUC, compared to MIUC, was characterized by a lower median mutational burden (9.9 mut/Mb vs. 11.8 mut/Mb, respectively; p=0.037) and was associated with a higher rate of mutations of the FGFR/FGF (p=0.059) and STAG2/IRF (p=0.055) signaling pathways genes, as well as the FGFR3 (p=0.001) and STAG2 (p=0.026) genes with a lower rate of aberrations of the p53 signaling pathway genes (p=0.005), TP53 (p=0.001) and FGF4 (p=0.057). The low grade NMIUC samples had a lower rate of high mutational burden (vs. high grade NMIUC, p=0.004; vs high grade MIUC, p=0.067) and were also associated with a higher rate of FGF/FGFR signaling pathway gene mutations (vs. high grade MIUC, p<0.0001; vs. high grade NMIUC, p<0.0001), mainly due to FGFR3 alterations (vs. high grade NMIUC; p<0.0001; vs. high grade MIUC; p<0.0001). Low grade NMIUC, compared to high grade MIUC, had a higher rate of PIK3CA (p=0.027) and KDM6A (p=0.001) mutations. The mutational profile of high grade NMIUC and high grade MIUC did not differ significantly. High grade MIUC, compared to low grade NMIUC had a higher rate of mutations of the p53 pathway genes (p=0.008), including TP53 (p=0.001), and a significantly lower rate of alterations of the FGF/FGFR signal pathway genes (p<0.0001), including FGFR3 (p<0.0001), as well as the STAG2/IRF pathway genes (p=0.035) and the PIK3CA gene (p=0.027).

Conclusion. Differences of the histological structure and natural history of low grade NMIUC, high grade NMIUC, and high grade MIUC are due to significant differences in their mutational status. NMIUC has a high rate of mutations in genes of the FGF/FGFR signaling pathway and inactivating mutations in STAG2 and KDM6A genes. MIUC typically has driver mutations that inactivate the p53 signal pathway. High grade NMIUC has alterations typical for both NMIUC (FGF/FGFR pathway gene mutations) and MIUC (p53 pathway gene mutations).

In the article «The reasons for prescribing antitumor drugs beyond the registered indications in real clinical practice: A retrospective study», published in the Journal of Modern Oncology, Vol. 26, No.4, 2024 (DOI: 10.26442/18151434.2024.4.203108), errors were made:

1. The number of used medicinal products (MPs) was corrected in the sentence "The use of 47 MPs was reported, including 46 antitumor agents and drugs with antitumor activity as part of 73 antitumor drug therapy regimens".

Correct wording of the sentence:

"The use of 46 MPs as part of 73 antitumor drug therapy regimens was reported".

2. The names of 3 drugs and 1 applied regimen in 4 rows of the table have been corrected.

The errors were corrected at the request of the authors' team. The publisher replaced the original version of the published article with the corrected one; the information on the website was also corrected.

The publisher apologizes to readers and authors for the errors and is confident that the correction of errors will ensure the correct perception and interpretation of the results of the study described in the text.