Impact of Therapy in Patients with Hematologic Malignancies on Seroconversion Rates After SARS-CoV-2 Vaccination.

INTRODUCTION: The leading professional organizations in the field of hematology have recommended severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) vaccination for all patients with hematologic malignancies notwithstanding efficacy concerns. Here we report a systematic literature review regarding the antibody response to SARS-CoV-2 vaccination in patients with hematologic malignancies and its key determinants. METHODS: We conducted a systematic search of original articles evaluating the seroconversion rates with SARS-CoV-2 vaccines in hematological malignancies from the PubMed database published between April 1, 2021 and December 4, 2021. Calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between patients with hematologic malignancies versus healthy control subjects used the Review Manager software, version 5.3. RESULTS: In our meta-analysis, we included 26 studies with control arms. After the first dose of vaccination, patients with hematologic malignancies had significantly lower seroconversion rates than controls (33.3% vs 74.9%; RD: -0.48%, 95% CI: -0.60%, -0.36%, P < .001). The seroconversion rates increased after the second dose, although a significant difference remained between these 2 groups (65.3% vs 97.8%; RD: -0.35%, 95% CI: -0.42%, -0.28%, P < .001). This difference in seroconversion rates was particularly pronounced for Chronic Lymphocytic Leukemia (CLL) patients (RD: -0.46%, 95% CI: -0.56, -0.37, P < .001), and for patients with B-lineage leukemia/lymphoma treated with anti-CD20 antibodies (RD: -0.70%, 95% CI: -0.88%, -0.51%, P < .001) or Bruton Tyrosine Kinase Inhibitors (BTKi; RD: -0.63%, 95% CI: -0.85%, -0.41%, P < .001). The RD was lower for patients under remission (RD: -0.10%, 95% CI: -0.18%, -0.02%, P = .01). CONCLUSION: The seroconversion rates following SARS-CoV-2 vaccination in patients with hematologic malignancies, especially in CLL patients and patients treated with anti-CD20 antibodies or BTKi, were significantly lower than the seroconversion rates in healthy control subjects. Effective strategies capable of improving vaccine efficacy in these vulnerable patient populations are urgently needed.

The burden of polypharmacy and drug-drug interactions in older cancer patients treated with immunotherapy.

INTRODUCTION: Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. METHODS: A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. RESULTS: The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). CONCLUSION: In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

Antibody Responses to COVID-19 Vaccination in Cancer: A Systematic Review.

INTRODUCTION: After the results of phase III vaccine studies became available, the leading oncology societies recommended two doses of COVID-19 vaccination to all patients with cancer with no specific recommendation for tumor type and active treatments. However, the data on the COVID-19 vaccine efficacy in cancer patients is limited due to exclusion of cancer patients from most vaccine clinical trials. Therefore, we systemically reviewed the available evidence evaluating the antibody responses in cancer patients. METHODS: We conducted a systematic search from the Pubmed database and calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between cancer patients and controls using the Review Manager software, version 5.3. RESULTS: Our systematic search retrieved a total 27 studies and we included 17 studies with control arms in the analyses. Cancer patients had significantly lower seroconversion rates (37.3%) than controls (74.1%) (RD: -0.44, 95% CI: -0.52, -0.35, p<0.001) with first vaccine dose. After two doses, the seroconversion rates were 99.6% in control arm and 78.3% in cancer patients (RD: -0.19, 95% CI: -0.28, -0.10, p<0.001). The difference in seroconversion rates was more pronounced patients with hematologic malignancies (72.6%) (RD: -0.25, 95% CI: -0.27, -0.22, p<0.001) than patients with solid tumors (91.6%) (RD: -0.09, 95% CI: -0.13, -0.04, p<0.003) and patients in remission (RD: -0.10, 95% CI: -0.14, -0.06, p<0.001). CONCLUSION: In conclusion, COVID-19 vaccine seroconversion rates were significantly lower in patients with hematological malignancies and patients under active treatment. Further research focusing on the approaches to improve vaccine efficacy and exploration of novel treatment options is urgently needed for these patients.

Lower prognostic nutritional index is associated with poorer survival in patients receiving immune checkpoint inhibitors.

Aim: Blood-based biomarkers like prognostic nutritional index (PNI) are readily available biomarkers for immunotherapy efficacy, although the data are limited. So, we aimed to evaluate the association between PNI and overall survival (OS) in immunotherapy-treated patients. Materials & methods: For this retrospective cohort study, data of 150 immunotherapy-treated advanced cancer patients were evaluated. The association between clinical factors and OS was evaluated with multivariate Cox-regression analyses. Results: After a median follow-up of 8.5 months, 94 patients died. The median OS was 11.07 months. The low PNI (hazard ratio [HR]: 2.065; p = 0.001), high lactate dehydrogenase (HR: 2.515; p = 0.001) and poor Eastern Cooperative Oncology Group (ECOG) status (HR: 2.164; p = 0.009) was associated with poorer OS in multivariate analyses. Conclusion: In our experience, survival with immunotherapy was impaired in patients with lower PNI and higher lactate dehydrogenase levels and poorer ECOG status.

Predictive biomarkers for immunotherapy efficacy in non-small-cell lung cancer: current status and future perspectives.

In recent years, immune checkpoint inhibitors have rapidly changed treatment paradigms and have been pivotal for the treatment of advanced NSCLC patients. However, many patients don't respond to immunotherapy, and toxicities are a concern. Mounting evidence suggests that PD-L1 expression and tumor mutational burden are useful biomarkers in NSCLC and widely used in clinical practice. Given various limitations of PD-L1 and tumor mutational burden, many candidate biomarkers have emerged. From these biomarkers, peripheral blood-based biomarkers are promising options for the prediction of immunotherapy efficacy with ease of access, repeatability and low cost. This review provides an overview of recent developments on the biomarkers in immunotherapy efficacy together with comments on future perspectives.

Prevention of DMBA-induced mammary gland tumors in mice by a dual-function inhibitor of JAK3 and EGF receptor tyrosine kinases.

Objectives: We tested the chemopreventive effect of WHI-P131 in side by side evaluation with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer model.Methods: One hundred BALB/cmice were divided into five groups. (i) Control (ii) DMBA (iii)  DMBA+ Paclitaxel (10 mg/kg) (iv)  DMBA+WHI-P131 (Janex1, 50 mg/kg of BW, i.p, three times per week) ("J") (v) DMBA+P+J. The duration of study was 25 weeks.Results: Our findings demonstrate that WHI-P131 impedes DMBA-induced carcinogenesis, reduces size, weight, and load of tumors (P < 0.001) in DMBA-challenged mice and improves their survival outcome (P < 0.01). The tumors developing despite WHI-P131 chemoprevention displayedattenuated levels of JAK3, STAT3, and NF-κB as well as increased I-κB expression (P < 0.001). Notably, these tumors exhibited significantly decreased levels of phosphorylated AKT-PI3-Kinase pathway signaling proteins p-mTOR, p-p70S6K1, and p-4E-BP1 (P < 0.001). Our findings are consistent with a model in which DMBA-induced malignant clones with low-level expression of the six signature proteins JAK3/STAT3/NF-κB/p-mTOR, p-p70S6K1/p-4E-BP1, albeit not as aggressive as their JAK3/STAT3/NF-κB overexpressing counterparts are capable of escaping chemo-preventive effects of WHI-P131.Conclusion: These insights may provide the foundation for new chemo-preventive strategies in which WHI-P131 is applied to prevent the development of aggressive forms of breast cancer.