Hematologic Events Research Articles

Experience of piloting BPaLM/BPaL for DR-TB care at selected sites in Pakistan.

Pakistan ranks fourth globally in terms of high drug-resistant TB (DR-TB) burden, with approximately one-third of cases resistant to fluoroquinolones. Bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM/BPaL) offers an opportunity for most DR-TB patients to benefit from a shorter, all-oral, well-tolerated and more effective treatment. We conducted a retrospective cohort study to pilot the BPaLM/BPaL regimen at four selected sites in two provinces of Pakistan, i.e. Punjab and Khyber Pakhtunkhwa. Data were extracted and analysed using electronic medical records from the program. Descriptive statistics, survival analysis and binary logistic regression analysis were employed. A total of 116 patients took treatment between October 2022 and February 2023. The treatment success rate was 96%, with 3% deaths and <1% loss to follow-up. Patients typically completed treatment in 26.2-26.7 weeks for BPaLM and BPaL, respectively. No serious adverse events were observed. The most common side effects included QTcF prolongation (BPaLM: 55%, BPaL: 84%), haematological events (BPaLM: 32%, BPaL: 34%), and gastrointestinal problems (BPaLM: 36%, BPaL: 25%). The BPaLM/BPaL regimens for DR-TB are highly effective with minimal adverse events and feasible to implement in routine program circumstances.

Effect analysis of 847 nasopharyngeal carcinoma cases treated with intensity modulated radiation: Experience and suggestions

ObjectivesTo identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. MethodsData on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed. ResultsThe 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome. ConclusionNPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local–regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied.

COVID-19 vaccination and major cardiovascular and haematological adverse events in Abu Dhabi: retrospective cohort study

The widespread administration of COVID-19 vaccines has prompted a need to understand their safety profile. This investigation focuses on the safety of inactivated and mRNA-based COVID-19 vaccines, particularly concerning potential cardiovascular and haematological adverse events. A retrospective cohort study was conducted for 1.3 million individuals residing in Abu Dhabi, United Arab Emirates, who received 1.8 million doses of the inactivated BBIBP CorV (by SinoPharm) and mRNA-based BNT162b2 (Pfizer-BioNTech) vaccines between June 1, 2021, and June 30, 2022. The study’s primary outcome was to assess the occurrence of selected cardiovascular and haematological events leading to hospitalization or emergency room visits within 21 days post-vaccination. Results showed no significant increase in the incidence rates of these events compared to the subsequent 22 to 42 days following vaccination. Analysis revealed no elevated risk for adverse outcomes following first (IRR 1·03; 95% CI 0·82-1·31), second (IRR 0·92; 95% CI 0·72-1·16) and third (IRR 0·82; 95% CI 0·66-1·00) doses of either vaccine. This study found no substantial link between receiving either mRNA and inactivated COVID-19 vaccines and a higher likelihood of cardiovascular or haematological events within 21 days after vaccination.

Rituximab, chidamide, and zanubrutinib (ZCR) ± CHOP as a regimen for treatment naive (TN) double-expressor DLBCL (DE-DLBCL).

e19053 Background: DLBCL patients with co-expression of MYC (≥40%) and BCL2 (≥50%) by immunohistochemistry are considered as DE-DLBCL. The prognosis of DE-DLBCL is usually worse than DLBCL-NOS. The Smart Start trial had established the feasibility of chemotherapy-free targeted therapy before 1L chemotherapy. The BTK inhibitor Zanubrutinib (Z) or epigenetic drug Chidamide (C) with R-CHOP regimen has a potential synergistic effect in the treatment of DE-DLBCL. Under the inspiration of Smart Start, this trial aim to explore the feasibility of ZCR±CHOP regimen in TN DE-DLBCL. Methods: This is a multicenter, open-label, single-arm phase 2 study (NCT05527912) conducted in China. If patients achieve complete response (CR) after cycle-2 (C2), ZCR will be continued for up to 8 cycles. Otherwise, ZCR-CHOP will be given for another 6 cycles. The primary endpoint is CR rate at the end of treatment (CRR-EOT); secondary endpoints included ORR (overall response rate) ,2y-PFS, and 2y-OS. Plasma samples were collected at baseline, C2 and the EOT. In evaluable samples, circulating tumor DNA (ctDNA) assays were performed. Results: From February 2023 till now, 34 TN DE-DLBCL patients were enrolled, with 32 patients evaluable. The median age was 52y (range: 22-68), 55.9% were male, 79.4% were Non-GCB (Table 1). 12 patients who achieved CR by C2 were continued with RCZ chemo-free therapy, and CHOP were added to the 14 PR and 3 SD patients. In the 32 evaluable patients, ORR after C2 of RCZ was 81.25% (26/32, CR 37.5%, PR 43.75%, SD 9.4%, PD 9.4%). Up to now, 12 patients have completed 8 courses (C8) and all of them have achieved CR, both ORR and CR are 100% (12/12). 3 patients withdrew due to PD. For safety information in the trial, 64.3% patients reported grade (G)-3/4 AEs. In the Chemo-Free subgroup, only 4 patients (36.4%, 4/11) reported G-3/4 AEs. the majority of G-3/4 AEs is hematological events, including leukopenia, neutropenia and thrombocytopenia. The CR rate at C2 was 66.7% (6/9) in patients with negative baseline ctDNA results. The patients with BCL6 fusion of ctDNA at baseline were more prone to PD (3/4, 75.0%). Compared to baseline, plasma ctDNA levels decreased significantly after C2. 29 patients were evaluable for ctDNA after C2, 100% (12/12) of C2-CR patients and 58.8% (10/17) of non-C2-CR patients were negative, P=0.023. Compared with Non-C2-CR patients, the number of detected mutations and average VAF level were decreased in C2-CR patients. Conclusions: This trial demonstrates ZCR±CHOP could be a promising regimen with active antitumor effect and acceptable toxicity in TN DE-DLBCL patients. Clinical trial information: NCT05527912 .

Adverse Event Profile of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non-small Cell Lung Cancer: An Updated Meta-analysis.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer. An updated toxicity profile of EGFR-TKIs proves valuable in guiding clinical decision making. This study comprehensively assessed the risk of EGFR-TKI-related adverse events (AEs) involving different systems/organs. We systematically searched PubMed, Embase, Web of Science, and Cochrane library for phase III randomized controlled trials comparing EGFR-TKI monotherapy with placebo or chemotherapy in patients with non-small cell lung cancer. The odds ratio (OR) of all-grade and high-grade adverse events (AEs) including dermatologic, gastrointestinal, hematologic, hepatic, and respiratory events was pooled for a meta-analysis. Subgroup analyses based on the control arm (placebo or chemotherapy) and individual EGFR-TKIs (erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib) were conducted. Thirty-four randomized controlled trials comprising 15,887 patients were included. The pooled OR showed EGFR-TKIs were associated with a significantly increased risk of all-grade dermatologic AEs including paronychia, pruritus, rash, skin exfoliation, and skin fissures, gastrointestinal AEs including abdominal pain, diarrhea, dyspepsia, mouth ulceration, and stomatitis, hepatic AEs including elevated alanine aminotransferase and aspartate aminotransferase, and respiratory AEs including epistaxis, interstitial lung disease and rhinorrhea. Furthermore, a significantly increased risk of high-grade rash (OR 7.83, 95% confidence interval [CI] 5.11, 12.00), diarrhea (OR 2.10, 95% CI 1.44, 3.05), elevated alanine aminotransferase (OR 3.93, 95% CI 1.71, 9.03), elevated aspartate aminotransferase (OR 3.22, 95% CI 1.05, 9.92) and interstitial lung disease (OR 2.35, 95% CI 1.38, 4.01) was observed in patients receiving EGFR-TKIs. When stratified by individual EGFR-TKIs, gefitinib showed a significant association with all-grade and high-grade hepatotoxicity and interstitial lung disease. Epidermal growth factor receptor tyrosine kinase inhibitors were associated with a significantly increased risk of various types of AEs. Clinicians should be vigilant about the risks of these EGFR-TKI-related AEs, particularly for severe hepatotoxicity and interstitial lung disease, to facilitate early detection and proper management.

Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial

A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC. This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m2 on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on cycle 1-day 1, and 250 mg/m2 subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m2 was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed. Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%). The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE. French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC. For the French translation of the abstract see Supplementary Materials section.

Case report: NSCLC with pulmonary embolism after treatment with almonertinib

Rationale: Almonertinib is the first independently developed third generation epidermal growth factor receptor tyrosine kinase inhibitors in China. It can be used not only for epidermal growth factor receptor (EGFR) sensitive mutation patients but also for T790M (+) resistant patients, and has better safety and survivability compared to the first and second generation EGFR-TKIs. The previous literature and case studies have reported significant treatment-related adverse reactions in non-small cell lung cancers patients treated with almonertinib, including elevated blood creatine phosphatase, prolonged cardiac QT interval, altered myocardial contractility, interstitial lung disease, eye disease, and hematological events. But there are few individual reports of pulmonary embolism events. Patient concerns: A 55-year-old female with no history of smoking visited a local hospital with mild cough and lower sacrococcygeal pain without obvious cause. Diagnosis: She was diagnosed with right lung adenocarcinoma with multiple bone metastases (T2bN1M1c, stage IVB) after image and histological examination, with EGFR 21 exon L858R sensitive mutation. Interventions: She initially underwent surgical treatment due to the discovery of a sacral tumor, and the pathology of the surgery indicated metastatic lung adenocarcinoma. Genetic testing results showed EGFR 21 exon L858R sensitive mutation. Combined with positron emission tomography/computed tomography imaging results and sacral tumor surgical pathology results, it was considered that the patient had lung adenocarcinoma with multiple bone metastases. Treatment plan: targeted treatment with almonertinib which is the third-generation EGFR-TKIs. After only 1 month of targeted treatment, chest enhanced computed tomography revealed pulmonary embolism imaging, combined with coagulation indicators, considering pulmonary embolism. As the thromboembolic site is located at the end of the pulmonary artery branch and imaging shows that tumor lesions are stable. Consider continuing targeted treatment with almonertinib and adjuvant oral anticoagulant therapy with rivaroxaban for treatment. Outcomes: Two months later, the patient’s condition was followed up and it was found that the imaging manifestations of pulmonary embolism disappeared, but the coagulation indicators remained in a hypercoagulable state. The patient’s treatment plan remained unchanged, and the patient was hospitalized for follow-up every 6 to 8 weeks to closely observe changes in the condition. Lessons: There are many reasons for the occurrence of hypercoagulable blood in tumor patients, and there are very few reports of treatment-related pulmonary embolism events in patients who are treated with almonertinib targeted therapy. It is particularly important to determine whether the hypercoagulable blood in such patients is related to targeted therapy drugs in clinical practice, as this will affect the clinical benefits of patients in epidermal growth factor receptor tyrosine kinase inhibitors treatment and the clinical indicators which need to pay more attention in follow-up observation, to avoid serious pulmonary embolism events and thus affect the patient’s survival status and quality of life.

Janus kinase inhibitors and the changing landscape of vitiligo management: a scoping review.

Vitiligo is a chronic skin condition caused by an autoimmune response that results in the progressive loss of melanocytes and recent studies have suggested that Janus kinase inhibitors (JAKi) are emerging as a promising new treatment modality. Therefore, to assess and understand the extent of knowledge in the emerging field of JAKi use in vitiligo, a scoping review of the literature was undertaken. The reviewed articles explored a wide variety of JAKi administered either orally or topically for vitiligo. There were no injectable JAKi studied. Tofacitinib was the most commonly studied oral JAKi in 16 of the 35 studies selected for review, followed by baricitinib (n = 3), and one study each with ritlecitinib, ruxolitinib, and upadacitinib. Ruxolitinib (n = 6) and tofacitinib (n = 6) were the most often studied topical JAKi, followed by delgocitinib (n = 1). Potential benefits may vary between JAKi based on their receptor selectivity profile and coexistent autoimmune diseases. A topical JAKi would be advantageous in limited body area involvement and in adolescents. Concurrent use of JAKi with phototherapy or sun exposure appears beneficial. Most studies permitted the use of other topical agents. Acne-related events, though frequent yet mild, were reported with both oral and topical JAKi. Nasopharyngitis, upper respiratory tract infections, and headaches were the most common adverse effects seen in the larger trials with JAKi. No serious or clinically meaningful hematology or thromboembolic events were detected. Treatment of vitiligo with oral or topical JAKi seems to be promising and the growing evidence shows a favorable risk-benefit profile.

Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis.

This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

Safety and effectiveness of the radium-223-taxane treatment sequence in patients with metastatic castration-resistant prostate cancer in a global observational study (REASSURE).

Radium-223 and taxane chemotherapy each improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). Whether the radium-223-taxane sequence could extend survival without cumulative toxicity was explored. The global, prospective, observational REASSURE study (NCT02141438) assessed real-world safety and effectiveness of radium-223 in patients with mCRPC. Using data from the prespecified second interim analysis (data cutoff, March 20, 2019), hematologic events and overall survival (OS) were evaluated in patients who were chemotherapy-naive at radium-223 initiation and subsequently received taxane chemotherapy starting ≤90days ("immediate") or >90days ("delayed") after the last radium-223 dose. Following radium-223 therapy, 182 patients received docetaxel (172 [95%]) and/or cabazitaxel (44 [24%]); 34 patients (19%) received both. Seventy-three patients (40%) received immediate chemotherapy and 109 patients (60%) received delayed chemotherapy. Median time from last radium-223 dose to first taxane cycle was 3.6months (range, 0.3-28.4). Median duration of first taxane was 3.7months (range, 0-22.0). Fourteen patients (10 in the immediate and four in the delayed subgroup) had grade 3/4 hematologic events during taxane chemotherapy, including neutropenia in two patients in the delayed subgroup and thrombocytopenia in one patient in each subgroup. Median OS was 24.3months from radium-223 initiation and 11.8months from start of taxane therapy. In real-world clinical practice settings, a heterogeneous population of patients who received sequential radium-223-taxane therapy had a low incidence of hematologic events, with a median survival of 1year from taxane initiation. Thus, taxane chemotherapy is a feasible option for those who progress after radium-223. ClinicalTrials.gov identifier NCT02141438. Radium-223 and chemotherapy are treatment options for metastatic prostate cancer, which increase survival but may affect production of blood cells as a side effect. We wanted to know what would happen if patients received chemotherapy after radium-223. Among the 182 men treated with radium-223 who went on to receive chemotherapy, only two men had severe side effects affecting white blood cell production (neutropenia) during chemotherapy. On average, the 182 men lived for 2years after starting radium-223 and 1year after starting chemotherapy. In conclusion, patients may benefit from chemotherapy after radium-223 treatment without increasing the risk of side effects.

Single Ventricular Assist Device Care and Outcomes for Failed Stage I Palliation: A Single-Center Decade of Experience.

Single ventricular assist device (SVAD) use before and after stage I palliation (S1P) is increasing with limited data on outcomes. To address this knowledge gap, we conducted a single-center retrospective review to assess pre- and post-SVAD clinical status, complications, and outcomes. We leveraged a granular, longitudinal, local database that captures end-organ support, procedural interventions, hematologic events, laboratory data, and antithrombotic strategy. We identified 25 patients between 2013 and 2023 implanted at median age of 53 days (interquartile range [IQR] = 16-130); 80% had systemic right ventricles and underwent S1P. Median SVAD days were 54 (IQR = 29-86), and 40% were implanted directly from ECMO. Compared to preimplant, there was a significant reduction in inotrope use ( p = 0.013) and improved weight gain ( p = 0.008) post-SVAD. Complications were frequent including bleeding (80%), stroke (40%), acute kidney injury (AKI) (40%), infection (36%), and unanticipated catheterization (56%). Patients with in-hospital mortality had significantly more bleeding complications ( p = 0.02) and were more likely to have had Blalock-Thomas-Taussig shunts pre-SVAD ( p = 0.028). Survival to 1 year postexplant was 40% and included three recovered and explanted patients. At 1 year posttransplant, all survivors have technology dependence or neurologic injury. This study highlights the clinical outcomes and ongoing support required for successful SVAD use in failed single-ventricle physiology before or after S1P.

Bladder-Preserving Trimodality Therapy With Capecitabine

IntroductionMany patients with muscle-invasive bladder cancer are poor candidates for radical cystectomy or trimodality therapy with maximal transurethral resection of bladder tumor (TURBT) and chemoradiotherapy with cisplatin or mitomycin C. Given the benefit of chemotherapy in bladder-preserving therapy, less-intense concurrent chemotherapy regimens are needed. This study reports on efficacy and toxicity for patients treated with trimodality therapy using single-agent concurrent capecitabine. Materials and MethodsPatients deemed ineligible for radical cystectomy or standard chemoradiotherapy by a multidisciplinary tumor board and patients who refused cystectomy were included. Following TURBT, patients received twice-daily capecitabine (goal dose 825 mg/m2) concurrent with radiotherapy to the bladder +/˗ pelvis depending on nodal staging and patient risk factors. Toxicity was evaluated prospectively in weekly on-treatment visits and follow-up visits by the treating physicians. Descriptive statistics are provided. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival were estimated using the Kaplan-Meier method. ResultsTwenty-seven consecutive patients met criteria for inclusion from 2013 to 2023. The median age was 79 with 9 patients staged cT3-4a and 7 staged cN1-3. The rate of complete response in the bladder and pelvis was 93%. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival at 2 years were estimated as 81%, 65%, 91%, 75%, and 92%, respectively. There were 2 bladder recurrences, both noninvasive. There were 7 grade 3 acute hematologic or metabolic events but no other grade 3+ toxicities. ConclusionMaximal TURBT followed by radiotherapy with concurrent capecitabine offers a high rate of bladder control and low rates of acute and late toxicity.

Comparative safety of novel targeted therapies in relapsed/refractory chronic lymphocytic leukemia: a network meta-analysis.

The emergence of new antileukemic drugs, including Bruton tyrosine kinase inhibitors (BTKis), phosphoinositide 3-kinase inhibitors (PI3Kis), and B-cell lymphoma 2 antagonists (BCL-2a), has significantly improved the outcomes for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Despite advances in treatment efficacy, the comprehensive safety profile of these novel agents versus traditional chemotherapy and immunotherapy has not been adequately explored, and there have been few direct comparisons. This study aimed to compare the safety profiles of novel therapeutic agents, chemotherapy, and immunotherapy in patients with relapsed/refractory CLL using a Bayesian network meta-analysis (NMA). A systematic literature review was conducted to identify randomized clinical trials on relapsed/refractory CLL. The search encompassed major medical databases (MEDLINE, Embase, and CENTRAL) and gray literature, with the aim to integrate the findings into a Bayesian NMA framework for safety outcome assessment. Systematic literature review with Bayesian NMA. The systematic search identified 14 randomized trials that formed networks for the comparison of safety outcomes. No differences were shown between therapies in terms of overall adverse events (AEs). However, bendamustine + rituximab had a more favorable safety profile for grade ⩾3 AEs when compared with ibrutinib (risk ratio 0.62 (95% credible interval 0.40-0.86)), acalabrutinib (0.69 (0.45-0.94)), zanubrutinib (0.64 (0.42-0.91)), and venetoclax + rituximab (0.87 (0.79-0.96)). The frequency of grade ⩾3 AEs, serious AEs, and treatment discontinuations and deaths due to AEs was comparable between acalabrutinib, zanubrutinib, and venetoclax + rituximab. There were no significant differences in the safety profiles regarding hematological events, events affecting the quality of life, and infections for most comparisons of venetoclax + rituximab with BTKis. Among BTKi-specific events, zanubrutinib was associated with a higher risk of hypertension (2.96 (1.74-5.16)) and bleeding (1.38 (1.06-1.81)) than acalabrutinib. No differences in the risk of atrial fibrillation were found between acalabrutinib and zanubrutinib (1.56 (0.74-3.34)). Our findings showed that venetoclax + rituximab, acalabrutinib, and zanubrutinib have acceptable safety profiles, which indicates that they may be the preferred therapeutic options in the setting of relapsed/refractory CLL. PROSPERO CRD42022304330.

Carboplatin in metastatic castration-resistant prostate cancer patients with molecular alterations of the DNA damage repair pathway: the PRO-CARBO phase II trial.

DNA damage repair genes are altered in 20-35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination repair (HRR) deficiency. These alterations could also predict platinum sensitivity. Although carboplatin was inconclusive in unselected mCRPC, the literature suggests an anti-tumoral activity in mCRPC with HHR gene alterations. We aimed to assess the efficacy of carboplatin monotherapy in mCRPC patients with HRR deficiency. This prospective multicenter single-arm two-stage phase II addressed mCRPC men with HRR somatic and/or germline alterations, pretreated with ⩾2 taxane chemotherapy regimens and one androgen receptor pathway inhibitor. Prior PARPi treatment was allowed. Enrolled patients received intravenous carboplatin (AUC5) every 21 days for 6-9 cycles. The primary endpoint was the best response rate according to adapted PCWG3 guidelines: radiological response (RECIST 1.1 criteria) and/or biological response [⩾50% prostate-specific antigen (PSA) decline]. A total of 15 out of 16 enrolled patients started carboplatin treatment. Genomic alterations were identified for BRCA2 (n = 5), CDK12 (n = 3), ATM (n = 3) CHEK2 (n = 2), CHEK1 (n = 1), and BRCA1 (n = 1) genes. Objective response (partial biological response + stable radiological response) was achieved in one patient (6.7%), carrying a BRCA2 mutation and not pre-treated with PARPi; stable disease was observed for five patients (33.5%). Among seven patients (46.7%) with previous PARPi treatment, four patients (57.1%) had a stable disease. The median progression-free and overall survivals were 1.9 [95% confidence interval (95% CI), 1.8-9.5] and 8.6 months (95% CI, 4.3-19.5), respectively. The most common severe (grade 3-4) treatment-related toxicities were thrombocytopenia (66.7%), anemia (66.7%), and nausea (60%). Overall, 8 (53.3%) patients experienced a severe hematological event. The study was prematurely stopped as pre-planned considering the limited activity of carboplatin monotherapy in heavily pre-treated, HHR-deficient mCRPC patients. Larger experience is needed in mCRPC with BRCA alterations. NCT03652493, EudraCT ID number 2017-004764-35.

Abstract B160: A phase 1 open-label, dose-escalation study of central nervous system–penetrant cyclin-dependent kinase (CDK)4/6 inhibitor PRT3645 in patients with select advanced or metastatic solid tumors

Abstract Introduction: CDK4/6 mediate cell cycle progression and are important for cancer initiation, growth, and survival. CDK4/6 inhibitors are approved for patients with advanced HR+/HER2– breast cancer but are ineffective against primary or metastatic brain tumors. PRT3645 is an investigational, highly selective, and potent CDK4/6 inhibitor, designed to achieve high tissue and brain penetration. This phase 1 dose-escalation study (NCT05538572) aims to evaluate safety, preliminary efficacy, and pharmacokinetic/pharmacodynamic profile of PRT3645. Methods: Patient eligibility criteria include: age ≥18 years; Eastern Cooperative Oncology Group/Karnofsky performance status ≤1/≥80; adequate organ function; histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy: breast cancer (HR+/HER2– or HR+/HER2+), glioblastoma (isocitrate dehydrogenase [IDH] wild type), CDKN2A/B homozygous deleted IDH–mutant astrocytoma, non-small cell lung cancer (KRAS mutant), or select solid tumors with CDK pathway alterations; and progression on, ineligibility for, or refusal of standard therapy. Patients with treated and untreated brain metastases (lesion &amp;lt;1.5 cm) could enroll if they had no neurological symptoms and did not require immediate local treatment. PRT3645 was taken orally once daily for 28 days (1 cycle) with dose escalation employing a Bayesian optimal interval design to evaluate the safety, tolerability, incidence of dose-limiting toxicities, and pharmacokinetic/pharmacodynamic profile. Results: At data cutoff (May 18, 2023), 8 patients received 20 and 40 mg once daily (first 2 dose levels of dose escalation). No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. Median age was 62 (range, 53-76) years; 50% of patients were male; in these early dose cohorts 75% of patients discontinued therapy (all due to progressive disease; median duration of therapy: 8 [range, 4-16] weeks); 5 patients had glioblastoma, 2 had breast cancer, and 1 had sarcoma. All-cause, any-grade adverse events (AEs) reported in ≥1 patients were anemia and dizziness. One grade 1 AE (fatigue) was considered related to PRT3645. No patients had grade ≥3 AEs, serious AEs, diarrhea, QTcF prolongation, or hepatotoxicity. No patients had dose reductions, interruptions, withdrawals, or deaths due to AEs. Between pre-dose and 2 weeks post first dose, a reduction in phosphorylated Rb (&amp;gt;70% in 3/4 patients) and Ki67 (&amp;gt;60% in 2/4 patients) expression was seen at 40 mg; both markers showed a correlation between histochemical score and drug exposure. Conclusions: Treatment with the next-generation CDK4/6 inhibitor PRT3645 was associated with a substantial decrease in phosphorylated Rb and Ki67 expression, indicating a high level of target engagement at a low dose. PRT3645 exhibited tolerable dose escalation in the initial 2 cohorts of patients with no significant gastrointestinal or hematologic events reported to date, leveraging its enhanced selectivity profile. Dose escalation is ongoing. Citation Format: Amita Patnaik, Mohamad A. Salkeni, Manish R. Patel, Atrayee Basu-Mallick, Dale Shepard, Christine Lihou, William Sun, Jennifer Xavier, Sri Sahasranaman, Neelesh Sharma, Erika Hamilton. A phase 1 open-label, dose-escalation study of central nervous system–penetrant cyclin-dependent kinase (CDK)4/6 inhibitor PRT3645 in patients with select advanced or metastatic solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B160.

Efficacy of Venetoclax Combined with Decitabine Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in High-Risk and Elderly Patients with Myeloid Neoplasms

Background High-risk and elderly patients with myeloid neoplasms are a special group because it's challenging to find the right balance between safety and efficacy during the peri-transplant period. Traditional transplant protocols have unsatisfactory treatment outcomes for patients with a high risk of recurrence, while the elderly couldn't tolerate the toxicity of high-dose chemotherapy drugs. Thus, new regimens are needed to improve treatment outcomes for high-risk and elderly patients. Through BCL-2 binding, venetoclax could induce leukemia cell apoptosis, increase chemosensitivity, and perform a synergistic role with HMAs. And its combination with HMAs or other cytotoxic drugs showed a promising effect on R/R AML. This prospective clinical study reported the efficacy and safety of adding venetoclax and decitabine to myeloablative conditioning regimens in high-risk and elderly patients receiving allogeneic hematopoietic stem cell transplantation. Methods We performed an investigator-initiated, prospective, one-arm, single-center, open-label trial. In total, 19 patients were enrolled in the trial between December 2021 and February 2023. Eligible patients met the following inclusion criteria: (1) undergoing allo-HSCT over the age of 50 years (i.e., ≥50 years), (2) having an Eastern Cooperative Oncology Group performance status of 0-2, and (3) having AML, MDS, and CMML with a high risk of recurrence: (a) For patients with MDS, (i) a diagnosis of MDS with excess blasts 2 (EB-2), (ii) a poor karyotype, (iii) a very high-risk disease according to the International Prognostic Scoring System-Revised, and (iv) a TP53 mutation; (b) For patients with AML, (i) relapsed/refractory AML, (ii) detected MRD test before transplantation, (iii) with adverse risk according to the European Leukemia Net (ELN) Guidelines 2017, and (iv) AML transformed from MDS or CMML. Venetoclax was administered at 400 mg per day orally from day -14 to day -1 in the initial regimen and from day -14 to day -5 in the modified regimen. Decitabine was administered at 20mg/m 2/d orally from day -7 to day -3. Detailed dosage of the Bu/Flu/Cy comprised of fludarabine 30 mg/m 2/d IV Qd, day -4 to -2, busulfan 3.2 mg/kg/d IV Q6h, day -7 to -5, and cyclophosphamide 40mg/kg/d IV Qd, day -3 to day -2. Either rabbit ATG or porcine ATG was administered at 2.5mg/kg/d IV Qd, day -4 to -1, or 20mg/kg/d IV Qd, day -3 to -1 for GVHD prophylaxis. Results 19 patients were enrolled in the trial with a median follow-up time of 258 (range, 35-544) days. Grade 3/4 adverse events included hematological events, hypertension, infections, allergy, and increased amylase. The 30-day cumulative incidence of neutrophil and platelet engraftment was 100% and 68% (Figure 1A). Acute GVHD occurred in 9 of 19 patients (grade I, n=2; grade II, n=1; grade III, n =4; grade IV, n =2). The cumulative incidence of grade II to IV acute GVHD events at 100 days was 31% (95% confidence interval (CI], 12-53) among all patients, and 45% (95% CI, 15-72), and 13% (95% CI, 0-45) for the initial regimen group and the modified regimen group, respectively (p=0.28, Figure 1B, C). While 1 patient in the modified regimen group occurred diarrhea and was clinically diagnosed with grade III acute GVHD (late-onset) at 132 days post-HSCT. The cumulative incidence of chronic GVHD at 1 year was 37% (95% CI, 16-58). For the entire cohort, OS and RFS at 6 months was 63% (95% CI, 45-89) and 63% (95% CI, 45-89), and the NRM and CIR at 6 months was 37% (95% CI, 16-58) and 0, respectively (Figure 1D, E). All 8 deaths were attributed to transplant-related complications, including 4 patients from aGVHD, 2 patients from infection, 1 from transplant-associated thrombotic microangiopathy (TA-TMA) and 1 from bloody pleural effusion. Here it should be pointed out that the patient with bloody pleural effusion couldn't exclude the probability of tumor invasion because he had previous esophageal carcinoma. Conclusion In conclusion, although the hematological and molecular recurrence rate of the venetoclax combined with the decitabine conditioning regimen is significantly decreased, the high incidence of severe aGVHD and NRM limits its clinical application. It still needs further exploration to optimize the conditioning regimen for high-risk and elderly patients with myeloid neoplasms.

Daratumumab, Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) Alone in Transplant-Ineligible Asian Patients with Newly Diagnosed Multiple Myeloma: Final Analysis of the Phase 3 Octans Study

Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action and has shown clinical efficacy for the treatment of multiple myeloma (MM). In an updated analysis of the global phase 3 ALCYONE study, D-VMP demonstrated a significant progression-free survival (PFS) benefit compared to VMP in transplant-ineligible patients with newly diagnosed MM (NDMM). A prior analysis of the phase 3 OCTANS study (median follow-up, 12.3 months) also showed a favorable clinical benefit/risk profile for D-VMP versus VMP in transplant-ineligible Asian patients with NDMM. Here, we report results from the final analysis of OCTANS, with a median follow-up of &amp;gt;3 years. Methods: The randomized, phase 3 OCTANS study (NCT03217812) enrolled Asian patients with NDMM who were ineligible for autologous stem-cell transplant due to age or presence of comorbidities. Patients were randomized 1:2 (VMP:D-VMP) to receive up to nine 42-day cycles of VMP (bortezomib 1.3 mg/m 2 SC twice weekly in Cycle 1 and weekly in Cycles 2-9, and melphalan 9 mg/m 2 and prednisone 60 mg/m 2 orally on Days 1-4 of each cycle) or D-VMP (VMP + daratumumab 16 mg/kg IV weekly in Cycle 1, every 3 weeks in Cycles 2-9, and every 4 weeks thereafter until disease progression). Per a protocol amendment, patients receiving daratumumab IV were permitted to switch to daratumumab SC 1,800 mg (same schedule as IV) on Day 1 of any cycle. The primary endpoint was achievement of a very good partial response (VGPR) or better. Results: A total of 220 patients were randomized to D-VMP (n = 146) or VMP (n = 74). At the time of the final analysis, with a median follow-up of 41.2 months, the rate of VGPR or better was significantly higher with D-VMP versus VMP (80.1% vs 47.3%; P &amp;lt;0.0001; Table). The rate of measurable residual disease negativity (10 -5) was also higher with D-VMP versus VMP (40.4% vs 10.8%; P &amp;lt;0.0001). D-VMP continued to show a significant improvement in PFS versus VMP (median, 38.7 vs 19.2 months; HR, 0.35; 95% CI, 0.23-0.52; P &amp;lt;0.0001; Table, Figure), as well as a longer time to subsequent antimyeloma therapy (median, 46.8 vs 20.6 months; HR, 0.31; 95% CI, 0.20-0.47; P &amp;lt;0.0001). However, median overall survival was not yet reached for either group. The overall safety profile of D-VMP was consistent with that observed for the primary analysis. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported for 133 (92.4%) patients who received D-VMP and 60 (84.5%) patients who received VMP and were primarily hematologic events; nonhematologic grade 3/4 TEAEs in ≥10% of patients included pneumonia (D-VMP, 31.3% vs VMP, 18.3%), hypokalemia (15.3% vs 4.2%), and hypertension (13.2% vs 8.5%). Grade 3/4 infection TEAEs were reported for 67 (46.5%) and 22 (31.0%) patients who received D-VMP or VMP, respectively. Serious TEAEs were reported for 75 (52.1%) and 28 (39.4%) patients in the D-VMP and VMP groups, respectively, and TEAEs led to treatment discontinuation in 6 (4.2%) and 4 (5.6%) patients, respectively. The incidence of infusion-related reaction TEAEs in the D-VMP group was 33.3%, which is consistent with that previously reported for daratumumab; most events were of grade 1 or 2 severity. The risk of immunogenicity to daratumumab was low, with 1 of 130 evaluable patients testing positive for daratumumab antibodies. Within the D-VMP group, 76 patients switched from daratumumab IV to SC administration. Among these patients, 64 (84.2%) patients preferred SC administration, 7 (9.2%) preferred IV administration, and 15 (19.7%) had no preference on ≥1 of 2 surveys. Of the 64 patients who preferred SC administration, primary reasons included treatment administration time (84.4%), more comfortable administration process (57.8%), less caregiver burden (31.2%), and fewer administration-related reactions (26.6%). Conclusions: With a median follow-up of &amp;gt;3 years, this final analysis of OCTANS demonstrated a continued clinical benefit with D-VMP versus VMP in Asian patients, with PFS improvement comparable to that observed in the global ALCYONE study (HR, 0.35 vs 0.42, respectively). No new safety concerns were identified for D-VMP with extended follow-up. In addition, daratumumab SC administration was preferred by the majority of patients who switched from daratumumab IV. These results further support the use of daratumumab IV or SC in combination with VMP in transplant-ineligible Asian patients with NDMM.

Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) Alone in Chinese Patients with Relapsed/Refractory Multiple Myeloma: Final Analysis of the Phase 3 Lepus Study

Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. D-Vd prolonged progression-free survival (PFS) and induced deeper and more durable responses versus Vd alone in patients with relapsed/refractory multiple myeloma (RRMM) in the global phase 3 CASTOR study. A prior updated analysis of the phase 3 LEPUS study (median follow-up, 25.1 months) showed significant clinical benefit for D-Vd versus Vd in Chinese patients who have RRMM, and a safety profile generally consistent with that observed in CASTOR. Here, we report results from the final analysis of LEPUS with an extended median follow-up of &amp;gt;3 years. Methods: In the randomized, multicenter, phase 3 LEPUS study (ClinicalTrials.gov Identifier: NCT03234972), Chinese patients with RRMM who had received ≥1 prior line of therapy were randomized 2:1 to 8 cycles (21 days/cycle) of Vd (bortezomib 1.3 mg/m 2 SC on Days 1, 4, 8, and 11; dexamethasone 20 mg PO/IV on Days 1, 2, 4, 5, 8, 9, 11, and 12) ± daratumumab (16 mg/kg IV weekly in Cycles 1-3, every 3 weeks in Cycles 4-8, and every 4 weeks thereafter until disease progression). Per a protocol amendment, on Day 1 of any cycle patients receiving daratumumab IV were permitted to switch to daratumumab SC 1800 mg (same schedule as IV). The primary endpoint was PFS. Results: A total of 211 patients were randomized to D-Vd (n = 141) or Vd (n = 70). At a median follow-up of 37.1 months, D-Vd continued to prolong PFS versus Vd alone (median, 14.9 vs 6.3 months; hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.25-0.52; P &amp;lt;0.00001; Figure 1). Time to progression (median, 15.7 vs 6.8 months; HR, 0.34; 95% CI, 0.23-0.51; P &amp;lt;0.00001) and overall survival (median, not reached vs 40.7 months; HR, 0.76; 95% CI, 0.50-1.17; P = 0.21; Figure 2) were longer with D-Vd versus Vd. The duration of response among patients who achieved a partial response or better was also longer with D-Vd versus Vd (median, 16.8 vs 9.0 months). The measurable residual disease-negativity rate (10 -5) was higher with D-Vd versus Vd (32.6% vs 4.3%; odds ratio, 10.81; 95% CI, 3.23-36.23; P &amp;lt;0.0001). The safety profile of D-Vd observed at the final analysis was generally consistent with that observed for the prior updated analysis. Grade 3/4 treatment-emergent adverse events (TEAEs) were primarily hematologic events. Grade 3/4 infections were reported for 77 (55.0%) patients who received D-Vd and 28 (41.2%) patients who received Vd; lung infection (30.7% vs 22.1%, respectively) was the only nonhematologic grade 3/4 TEAE reported in ≥20% of patients. For patients who received D-Vd and Vd, respectively, TEAEs were classified as serious for 76 (54.3%) and 27 (39.7%) patients, led to treatment discontinuation in 7 (5.0%) and 2 (2.9%) patients, and led to death in 6 (4.3%) and 7 (10.3%) patients. None of the 123 patients in the D-Vd group who had appropriate immunogenicity samples were positive for antibodies to daratumumab. A total of 31 patients in the D-Vd group switched from daratumumab IV to daratumumab SC during the study (after completion of bortezomib and dexamethasone); among these patients, 24 (77.4%) preferred SC administration, 2 (6.5%) preferred IV administration, and 5 (16.1%) had no preference. For the 24 patients who indicated they preferred daratumumab SC administration, key reasons for their preference included treatment administration time (83.3%), more comfortable administration process (70.8%), fewer administration-related reactions (45.8%), and less caregiver burden (25.0%). Among the 31 patients who switched to daratumumab SC, 6 (19.4%) patients experienced grade 3 TEAEs (most commonly hyperglycemia and hypokalemia, n = 2 each) and 2 (6.5%) patients experienced serious AEs (pyrexia and hyperglycemia, n = 1 each). Conclusions: In this final analysis of LEPUS with a median follow-up of &amp;gt;3 years, D-Vd continued to demonstrate substantial efficacy benefits versus Vd and the safety profile of D-Vd remained stable, with no new safety concerns identified. In addition, several patients switched their daratumumab administration from IV to SC, which was preferred by most patients who switched. These results further support the feasibility of daratumumab SC administration and the use of D-Vd as a standard of care in Chinese patients with RRMM who have received ≥1 prior line of therapy.

Efficacy of venetoclax combined with decitabine conditioning regimen for allogeneic hematopoietic stem cell transplantation in high-risk and elderly patients with myeloid neoplasms.

This prospective clinical investigation focused on the addition of venetoclax and decitabine to myeloablative conditioning regimens, targeting high-risk and elderly individuals undergoing allogeneic hematopoietic stem cell transplantation. In total, 19 patients were enrolled in the trial between December 2021 and February 2023, and their progress was monitored for a median follow-up period of 258 days, ranging from 35 to 544 days. In the initial regimen (n=11), venetoclax was administered at a dosage of 400 mg per day from day -14 to day -1, while in the modified regimen (n=8), it was administered from day -14 to day -5. Decitabine was orally administered at a dosage of 20mg/m2/day from day -7 to day -3. Grade 3/4 adverse events observed included hematological events, hypertension, infections, allergy, and increased amylase. In the entire cohort, the overall survival (OS) and relapse-free survival (RFS) rates at 6 months were 63% (95% CI, 45-89) and 63% (95% CI, 45-89), respectively. The non-relapse mortality (NRM) rate at 6 months was 37% (95% CI, 16-58), while the cumulative incidence of relapse (CIR) was 0. However, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD within 100 days was found to be 31% (95% CI, 12-53) and 26% (95% CI, 9-47), respectively. These rates indicate a relatively high occurrence, making it less suitable to administer the regimen to elderly patients. Therefore, further high-quality studies are required to enhance the conditioning regimen specifically for high-risk and elderly patients diagnosed with myeloid neoplasms. Clinical trial registration: ChiCTR2100050272.

Renal impairment as a risk factor for trifluridine/tipiracil-induced adverse events in metastatic colorectal cancer patients from the REGOTAS study

Renal impairment may be associated with an increased risk of hematologic events (AEs) in patients undergoing treatment with trifluridine/tipiracil (FTD/TPI). This study aimed to investigate the specific types of AEs linked to renal impairment in patients with metastatic colorectal cancer (mCRC) receiving FTD/TPI, using real-world data. Among the patients included in the REGOTAS study (a retrospective study of FTD/TPI versus regorafenib), those treated with FTD/TPI were evaluated. Creatinine clearance values of < 30, 30–60, 60–90, and > 90 mL/min were defined as severe, moderate, mild renal impairment, and normal renal function, respectively. Renal impairment was analyzed as a risk factor for grade 3 or higher AEs using a logistic regression model. Overall survival (OS) and progression-free survival (PFS) based on renal impairment were evaluated. A total of 309 patients were included in the analysis, with 124, 130, and 55 patients divided into the normal, mild, and moderate-to-severe groups, respectively. The risk of grade 3 or higher neutropenia was significantly higher in the moderate-to-severe group (odds ratio 3.47; 95% confidence interval 1.45–8.30; P = 0.005), but there was no significant increase in the risk of non-hematologic AEs in any of the groups. The OS and PFS of patients in the mild and moderate-to-severe groups were comparable to those in the normal group. Patients with mCRC and moderate/severe renal impairment receiving FTD/TPI therapy may develop severe neutropenia; however, FTD/TPI remains a viable treatment option due to its clinical benefit.