Comprehensive Evaluation of Drug-Related Problems and Pharmacotherapy Patterns in Non-Hodgkin’s Lymphoma Patients in Yemen

Chemotherapy-induced nausea and vomiting (CINV) is a prevalent and distressing adverse effect that can negatively affect a patient's quality of life and treatment adherence. This study aimed to evaluate the consistency of antiemetic use with standard guidelines and to examine the factors influencing it. This cross-sectional study was conducted at the National Oncology Center (NOC) of Al-Jomhouri Teaching Hospital, Sana'a, Yemen, from November 2022 to September 2023. Demographic data, chemotherapy and antiemetic regimens, dosages, and patient-related risk factors were collected via direct interviews, medical records, and treatment charts. This study evaluated the consistency of antiemetic practices among non-Hodgkin's Lymphoma (NHL) patients using the National Comprehensive Cancer Network (NCCN) guidelines. The chi-squared test and regression were used to determine the factors associated with guideline consistency. A total of 251 patients with NHL were recruited for the study; 57.4% were male and 60.6% were aged between 18-49. Most of the patients received moderately emetogenic chemotherapy (81.3%). The overall consistency with the NCCN guidelines was only 23.9%, with antiemetic drug selection and dosage reported inconsistently in 62.9% and 16.7% of patients, respectively. Furthermore, 62.5% of the patients received an under-prescribed antiemetic prophylactic regimen. Treatment duration, number of chemotherapy cycles, emetogenic risk potential, and overall patient risk, as well as age, sex, and marital status, were significantly associated with guideline inconsistency (p < 0.05). This study revealed a notable gap in the consistency of antiemetic prescriptions among patients with NHL. Inappropriate drug selection, dosing, and under-prescription are common problems. Patient regimen risk factors significantly influenced the consistency of the National Comprehensive Cancer Network guidelines. Personalized approaches are essential to enhance adherence to guidelines and improve antiemetic strategies.

National Comprehensive Cancer Network Guidelines: Who Makes Them? What Are They? Why Are They Important?

Several studies have shown the existence of an association between celiac disease (CD) and non-Hodgkin's lymphoma (NHL). Our aim was to evaluate the usefulness of the serum anti-tissue transglutaminase (anti-tTG) antibody assay in screening for CD in consecutive NHL patients. In all, 80 consecutive patients (median age 61 years) with a new diagnosis of NHL were included. To compare the frequency of CD and of positive results for the anti-tTG assay, we enrolled 500 blood donors. In all patients serum anti-tTG was determined with two different ELISA: one based on tTG from guinea pig (gp-tTG) and the other based on human recombinant t-TG (h-tTG) as the antigens. Serum anti-endomysial antibodies (EmA) were also assayed. Subjects with positive serum EmA and/or anti-tTG underwent intestinal biopsy for histology study, HLA-DQ phenotype determination, and serum anti-gliadin (AGA) assay. Eight of 80 (10%) NHL patients were positive for anti-tTG ELISA--two of these exclusively for anti-gp-tTG and six for anti-h-tTG (7.5%). None of the 80 NHL patients were positive for serum EmA. The frequency of anti-tTG positivity in the blood donor controls was 2/500 (0.4%), significantly lower than that observed in the NHL patients (P < 0.0001). Both these blood donors were found to have CD. Only in one anti-h-tTG-positive NHL patient was there intestinal mucosa atrophy, and follow-up confirmed a CD diagnosis (CD frequency in NHL patients is 1.2%; versus blood donors: P = 0.4). In all the other seven anti-tTG-positive NHL patients a normal intestinal architecture was found, although, inflammatory infiltration of the lamina propria was observed in four patients. No anti-tTG-positive NHL patients, including the subject diagnosed as having CD, had a family history of CD, and all had normal weight and no signs of malabsorption. Anti-tTG false positive results were associated with a higher frequency of serum autoantibody positivity and T-cell type NHL. In conclusion, NHL patients the anti-tTG assay often gives discordant data with the EmA assay, with a high frequency of anti-tTG false positive results for CD diagnosis.

Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.

Background: IRAK4, a serine/threonine kinase, was identified as a therapeutic target in hematological malignancies. IRAK4-mediated activation of NF-kappaB could play an important role in NF-kappaB-regulated survival and chemoresistance of cancer cells. CA-4948, a first-in-class small molecule inhibitor of IRAK4, has been tested in Phase 1 clinical trial with evidence of clinical activity in Non-Hodgkin's Lymphoma (NHL) patients. To support the development of companion diagnostic for CA-4948, we developed an immunohistochemical (IHC) assay and explored expression of potential biomarkers of response to CA-4948 in tumor biopsy samples obtained from NHL patients. Materials and Methods: IHC assay was developed and used for analysis of NF-kappaB p-p50 and p-IRAK1 expression in tumor biopsy samples obtained from 14 patients with NHL. Patients were defined according to their clinical response to CA-4948 treatment: stable disease (SD), 6 cases and progressive disease (PD), 8 cases. Results: We found nuclear and/or cytoplasmic expression of NF-kappaB p-p50 in all 6 SD cases treated with 50 mg QD (2 cases, tumor regression), 50 mg BID (1 case), 200 mg BID (1 case, tumor regression) and 400 mg BID (2 cases). Expression of NF-kappaB p-p50 was not detected in 7 of 8 cases with PD including patients treated with 50 mg QD (1 case), 100 mg QD (1 case), 100 mg BID (3 cases), 200 mg BID (1 case) and 400 mg BID (1 case). We found statistically significant correlation between expression of NF-kappaB p-p50 in tumor biopsy and SD in NHL patients treated with CA-4948 (p&amp;lt;0.05). Analysis of NF-kappaB p-p50 expression in paired tumor biopsy samples (3 cases) collected before and after the treatment with CA-4948 revealed a significant downregulation of NF-kappaB p-p50 expression in tumors obtained from CA-4948-treated NHL patients. In support of our in vivo findings, our in vitro experiments demonstrated that expression of NF-kappaB p-p50 was depleted in 3D lymphoma organoids treated with a clinically relevant concentration of CA-4948. Our results support further development of NF-kappaB p-p50 as a potential predictive and pharmacodynamic biomarker of IRAK4 inhibitor CA-4948. We found that expression of p-IRAK1 in tumor biopsies was not correlated with clinical response. Conclusions: Although the cohort size is small, our findings suggest that expression of NF-kappaB p-p50 can serve as biomarker to predict SD in response to the treatment with IRAK4 inhibitor CA-4948 in NHL patients. NF-kappaB p-p50 selection strategy might be used in future clinical trials to identify NHL patients which are most likely to respond to CA-4948 in combination with chemotherapy or targeted therapeutics. Citation Format: Andrey Ugolkov, Maria Samson, Rosanna Hok, Reinhard von Roemeling, Robert Martell. Identification of NF-kappaB phospho-p50 as a predictive biomarker for IRAK4 inhibitor CA-4948 in patients with non-Hodgkin's lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 385.

Cancer risk assessment models versus National Comprehensive Cancer Network guidelines: What is the most comprehensive method to assess cancer risk and triage for genetic testing? (373)

Clinical relevance of soluble HLA-I and β2-microglobulin levels in non-Hodgkin's lymphoma and Hodgkin's disease

A Population of Suppressive Monocytes Inhibiting T Cell Proliferation and Dendritic Cell Differentiation in Relapsed Non-Hodgkin's Lymphoma

Precision Adjuvant Therapy Based on Detailed Pathologic Risk Factors for Resected Oral Cavity Squamous Cell Carcinoma: Long-Term Outcome Comparison of CGMH and NCCN Guidelines

Therapy-related myelodysplastic syndromes and acute myeloid leukemia (t-MDS/AML), defined as MDS or AML occurring after myelosuppressive chemotherapy and/or radiation therapy, are devastating long-term complications of cancer therapy. White blood cell growth factors (CSFs) are supportive care agents intended to minimize risk of febrile neutropenia in patients receiving chemotherapy. However, evidence suggests that CSFs may increase risk of t-MDS/AML, possibly due to the observation that CSFs not only stimulate the proliferation and differentiation of hematopoietic stem cells, but also interfere with apoptosis. The purpose of this study was to evaluate the association between CSF use and t-MDS/AML among a large population-based cohort of elderly non-Hodgkin's lymphoma (NHL) patients treated with chemotherapy. We identified 13,203 NHL patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed from 1992 to 2002 who received chemotherapy within 12 months of diagnosis. Patients were followed from their initial chemotherapy date until t-MDS/AML development, death, or end of study period (October 31, 2006). Overall, 40% (n=5,266) of patients received CSF. A total of 272 (5.2%) of patients receiving CSF developed t-MDS/AML vs. 230 (2.9%) who did not receive CSF: there was a statistically significant higher incidence of t-MDS/AML among patients receiving CSF compared to patients not receiving CSF (log-rank p&amp;lt;0.0001). In a multivariable Cox regression analysis adjusting for gender, histology, stage, comorbidities, chemotherapy dates, and chemotherapy agent, CSF use was independently associated with a 53% increased risk of t-MDS/AML (HR 1.53; 95% CI 1.26 – 1.84). A dose-response relationship was observed, with t-MDS/AML risk increasing by quartile of CSF claims. In an evaluation of plausible biologic interactions, we found that patients who received both CSF and antimetabolite chemotherapy had a 2.5 fold increased risk of t-MDS/AML (HR 2.49; 95% CI 1.91 – 3.26) vs. patients who received neither agent (p-interaction=0.04). This observation has added clinical significance considering that approximately 10% of the overall population received this therapeutic combination. To our knowledge, this is the first large population-based study to evaluate the association between CSF use and t-MDS/AML risk among NHL patients. Findings support our hypothesis that the administration of CSF among elderly NHL patients receiving chemotherapy may increase the risk of t-MDS/AML, even though the absolute risk is low in these populations. Future studies are necessary to verify these results and to determine the potential clinical implications of the observed interaction between CSF use and antimetabolite chemotherapy. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B129.

Retrieval-Augmented GPT-4 Improves NCCN-Concordant Lymphoma Treatment Recommendations

Safety and Effectiveness of Rituximab Biosimilar CT-P10 during Routine Clinical Practice: Final Analysis of a Post-Marketing Surveillance Study in the Republic of Korea

Successful Stem Cell Remobilization Using Plerixafor (Mozobil) Plus Granulocyte Colony-Stimulating Factor in Patients with Non-Hodgkin Lymphoma: Results from the Plerixafor NHL Phase 3 Study Rescue Protocol

Based on their tumor-associated expression pattern, cancer/testis antigens (CTAs) are considered potential targets for cancer immunotherapy. We aim to evaluate the expression of CTAs in non-Hodgkin's lymphoma (NHL) samples and the ability of these patients to elicit spontaneous humoral immune response against CTAs. Expression of MAGE-A family, CT7/MAGE-C1, CT10/MAGE-C2, GAGE and NY-ESO-1 was analyzed by immunohistochemistry in a tissue microarray generated from 106 NHL archival cases. The humoral response against 19 CTAs was tested in 97 untreated NHL serum samples using ELISA technique. 11.3% of NHL tumor samples expressed at least 1 CTA. MAGE-A family (6.6%), GAGE (5.7%) and NY-ESO-1(4.7%) were the most frequently expressed antigens. We found no statistically significant correlation between CTA positivity and clinical parameters such as NHL histological subtype, Ann Arbor stage, international prognostic index score, response to treatment and overall survival. Humoral response against at least 1 CTA was observed in 16.5% of NHL serum samples. However, overall seroreactivity was low, and strong titers (>1:1000) were observed in only two diffuse large B-cell lymphomas patients against CT45. Our findings are in agreement with most of published studies in this field to date and suggest an overall low expression of CTAs in NHL patients. However, as many new CTAs have been described recently and some of them are found to be highly expressed in NHL cell lines and tumor samples, further studies exploring the expression of different panels of CTAs are needed to evaluate their role as candidates for immunotherapy in NHL patients.

Alterations of the p53 gene at 17p13.1 as well as the gene for a transmembrane p-glycoprotein, ABCB1 (MDR-1) at 7q21.12, have been shown to be mostly associated with the phenomenon of multi-drug resistance (MDR) in human cancers. In order to better understand the mechanisms by which chemoresistance is mediated, non-hodgkin's lymphoma (NHL) patients overexpressing p53 mutant protein and resistant to CHOP chemotherapy, NHL patients without p53 overexpression and a Burkitt's lymphoma Raji cell line with p53 overexpression have been evaluated using fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH). Three chromosomes (1, 7, and 17) known to be associated with MDR and the presence of p53 mutant protein, were analysed by FISH. No obvious chromosomal aberrations such as translocations were found in any of the patients when compared to healthy individuals, which suggests that the three selected chromosomes might not be specifically related to NHL, with or without p53 overexpression. For CGH, gains and losses of chromosomal material have been identified and the changes were not only limited to the three selected chromosomes associated with MDR. A detailed analysis of the recurrent aberrations shows that most of the NHL patients have alterations on the chromosome arms 1p, 6q, 7q, 20q, 22q, and Xp, whereas patients with p53 overexpression predominantly show aberrations on 4p and 17q. Further characterisation of the genetic regions identified might more closely contribute to our understanding of acquired MDR in NHL. Alterations in the three evaluated chromosomes may be prevalent in other tumours. In the present study, using FISH and CGH, there was insufficient difference between NHL patients with and without p53 overexpression.