Role of Serum Free Light Chain Assay in Relapsed/Refractory Multiple Myeloma. A Real-Life Unicentric Retrospective Study

Background: In the era of novel drugs a growing number of multiple myeloma (MM) patients are treated until disease progression. Serum free light chain (sFLC) assay is recommended for disease monitoring in oligo-secretory and micromolecular MM. Methods: In this real-life survey, a total of 130 relapsed/refractory MM patients treated at our center with at least three lines were investigated as a retrospective cohort. Results: The median age at diagnosis was 64 years and more than half of patients were male. A total of 24 patients (18%) had oligo-secretory/micromolecular disease at diagnosis. More than 20% of 106 normo-secretory patients had oligo-secretory/micromolecular escape. In order to evaluate potential role of sFLC assay before (“pre”) and after (“post”) every treatment line, involved serum free light chain values (iFLC) less than 138 mg/mL and serum free light chain ratios (FLCr) <25 were identified by using ROC curve analysis. The analysis of the entire cohort throughout four treatment lines demonstrated a statistically significant negative impact on progression-free survival (PFS) for both involved pre-sFLC and its ratio (respectively p = 0.0086 and p = 0.0065). Furthermore, both post-iFLC and post-FLCr greater than the pre-established values had a negative impact on PFS of the study cohort; respectively, p = 0.014 and p = 0.0079. Odds ratio analysis evidenced that patients with both involved post-sFLC greater than 138 mg/mL and post-FLCr above 25 at disease relapse had a higher probability of having clinical relapse (respectively p = 0.026 and p = 0.006). Conclusions: Alterations of sFLC values, namely iFLC and FLCr, both prior to treatment initiation and in the course of therapy at every treatment line, could be of aid in relapse evaluation and treatment outcome. We therefore suggest close periodical monitoring of sFLC assay, independently from secretory status.

Nationwide evaluation of mutation-tailored anti-EGFR therapy selection in patients with colorectal cancer in daily clinical practice

For a nationwide real-word data study on the application of predictive mutation testing of patients with colorectal cancer (CRC) for anti-epidermal growth factor receptor (EGFR) therapy stratification, pathology data were collected from the Dutch Pathology Registry from October 2017 until June 2019 (N=4060) and linked with the Netherlands Cancer Registry. Mutation testing rates increased from 24% at diagnosis of stage IV disease to 60% after 20–23 months of follow-up (p<0.001). Application of anti-EGFR therapy in KRAS/NRAS wild-type patients was mainly observed from the third treatment line onwards (65% vs 17% in first/second treatment line (p<0.001)). The national average KRAS/NRAS/BRAF mutation rate was 63.9%, being similar for next-generation sequencing (NGS)-based approaches and single gene tests (64.4% vs 61.2%, p=ns). NGS-based approaches detected more additional potential biomarkers, for example, ERBB2 amplifications (p<0.05). Therefore, single gene tests are suitable to stratify patients with mCRC for anti-EGFR therapy, but NGS is superior enabling upfront identification of therapy resistance or facilitate enrolment into clinical trials.

Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma

Background Atezolizumab plus bevacizumab therapy is the new standard treatment option for advanced hepatocellular carcinoma (HCC). The clinical details and sequential course after atezolizumab plus bevacizumab therapy remain to be determined. Methods From October 2020 to June 2021, 34 consecutive patients who received atezolizumab plus bevacizumab therapy were evaluated. Their clinical outcomes were assessed according to liver function classified by modified albumin-bilirubin (ALBI) grade 1 and 2a (1/2a) versus 2b and treatment line (first-line versus second- or later-line). Furthermore, the treatment sequence after atezolizumab plus bevacizumab therapy was also assessed. Results The objective response and disease control rates were 15.6% and 93.8%, respectively. The median proportions of ALBI scores at 1, 2, and 3 months relative to the baseline scores were 0.94, 0.97, and 0.93, respectively. The median proportions of α-fetoprotein (AFP) scores at 1, 2, and 3 months relative to the baseline scores were 0.98, 1.12, and 1.83, respectively. There were no significant differences in the changes in the proportions of AFP and ALBI scores according to both liver function and treatment line. Twelve patients were administered lenvatinib treatment after the failure of atezolizumab plus bevacizumab therapy. The proportions of AFP and ALBI scores at 1 month relative to the baseline scores were 0.55 and 0.81, respectively. Conclusions Atezolizumab plus bevacizumab therapy can be administered effectively for advanced HCC irrespective of patients’ liver function and treatment line. Lenvatinib administration after atezolizumab plus bevacizumab therapy can be effective, although special attention should be paid to the deterioration of liver function.

Management of Vipadika with Mahisha Gritha Padanimajjana – a case report

Objectives Vipadika (Palmo plantar Psoriasis) is a Kshudra Kushta (minor skin disorder) of Vatakapha origin (body humors like vata and kapha) characterized by Sphutana (cracks) and Teevra Vedana (severe pain) in Pani (palm) and Pada (sole). Based on the symptoms it can be correlated to Palmo Plantar Psoriasis which is a variant of psoriasis which affects the skin of the palms and soles with the features of hyperkeratotic, pustular, or mixed morphologies. The treatment methods for Palmo plantor psoriasis causes severe side effects due to which an evident shift from modern treatments to ayurvedic treatment line. Case presentation A 15 year old, female, with complaint of cracks and dryness over sole of both feet with pain for the last 12 and half years. The case was managed with Padanimajjana (immersion of foot). Padanimajjana is a modified form of Avagaha Sweda (switz bath) where the affected part of the foot is dipped in medicated liquid. Here Mahisha Gritha (Buffaloe ghee) is used for Padanimajjana. Conclusions Mahisha Gritha Padanimajjana shows significant improvement in number of cracks, dryness and pain within short period of time. This is a very simple, economical, and effective treatment for Vipadika.

The impact of antibiotic (Ab) exposure on clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI) or VEGF targeted therapy (VEGF-TT).

4552 Background: Retrospective studies have shown an association between Ab exposure and inferior clinical outcomes in patients receiving ICI across various tumor types, including mRCC. However, it is unclear whether Ab exposure has a unique interaction with ICI or is an independent prognostic marker, regardless of treatment. We sought to examine Ab exposure and its association with clinical outcomes in patients with mRCC treated with ICI compared to VEGF-TT. Methods: We identified patients treated with ICI (anti-PD-L1 alone or in combination with VEGF or CTLA4 inhibitor) or VEGF-TT alone in first to fourth line settings from 2009-2020 across 3 academic centers in North America. Ab exposure was defined as administration of Ab within 60 days prior to initiation of systemic therapy. Outcomes of interest were response rate (RR), time to treatment failure (TTF) and overall survival (OS). Multivariable Cox regression was performed to control for imbalances in International mRCC Database Consortium (IMDC) risk factors, histology, and treatment line. Results: We identified 748 patients. Among the ICI (n=427) and VEGF-TT (n=321) cohorts, 13% vs 15% (p=0.47) had Ab exposure and 57% vs 48% (p=0.046) were treated in the first line setting. The proportion of favorable, intermediate, and poor risk disease by IMDC criteria differed between Ab exposed and unexposed patients in the ICI (14% vs 18%, 47% vs 62%, 39% vs 21% p=0.03) and VEGF-TT (7% vs 13%, 43% vs 60%, 50% vs 27%, p=0.01) cohorts. RR, TTF and OS results are displayed in Table 1. Multivariable analysis did not show a significant independent association between Ab exposure and OS in both the ICI (HR 1.13, p=0.62) and VEGF-TT (HR 1.32, p=0.16) cohorts. Treatment modality (ICI vs VEGF-TT) did not modify the effect of Ab exposure on OS (p=0.84). Conclusions: Ab exposure was associated with higher IMDC risk scores in both the ICI and VEGF-TT cohorts as well as inferior OS on univariable analysis. After adjusting for IMDC risk factors, histology and treatment line, we were unable to find an independent association between Ab exposure and OS in multivariable analysis for either cohort.[Table: see text]

Response and outcomes to immune checkpoint inhibitors (ICI) in advanced urothelial cancer (aUC) based on prior intravesical BCG.

4537 Background: Little is known regarding response and outcomes to ICI for patients (pts) with aUC who were previously treated with BCG for non-muscle invasive bladder cancer. We hypothesized that prior intravesical BCG would not be associated with changes in objective response or survival in pts with aUC treated with ICI. Methods: We performed a retrospective cohort study across 25 institutions. Demographic, intravesical BCG history, treatment and outcomes data were collected for pts with aUC who received ICI. Pts with aUC treated with ICIs were included, pts with pure non-UC, those treated with combination or on clinical trials, pts with multiple ICI treatment lines and those with upper tract UC were excluded. Pts were stratified to prior exposure versus no exposure to BCG. We compared overall response rate (ORR) using logistic regression; and progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox proportional hazards. All analyses were performed in the overall population and further stratified by treatment line (first-line [1L] vs salvage [2+L]) and multivariable models. The stratified analysis was also adjusted for an internally developed risk score for 1L and Bellmunt risk score for 2+L; p<0.05 was significant. Results: 1026 aUC pts treated with ICI were identified; 614 pts, 617 pts, and 641 pts were included in ORR, OS and PFS analyses, respectively. Overall, mean age at CPI initiation was 70, 76% were men, 70% were current or former smokers, 75% White, 29% with mixed histology, and 24% had prior exposure to BCG. ORR to ICI in pts with or without prior exposure to BCG was similar, 27% and 28% respectively (OR=0.93 [95% CI 0.61-1.42], p=0.73). Median OS (mOS) for pts with vs without prior BCG exposure was 9 vs 10 mo (HR=1.13 [95% CI 0.88-1.44], p=0.35). Median PFS (mPFS) was 4 months (mo) in both groups (HR=1.02 [95% CI 0.82-1.27], p=0.83). ORR, PFS and OS analyses stratified by ICI treatment line (1L vs 2+L) are listed in the table. Conclusions: In this multi-institutional retrospective analysis, prior intravesical BCG was not associated with objective response or survival in pts with aUC treated with ICI. Limitations of this study include retrospective nature, lack of randomization and possible confounding, but it does provide important preliminary data that selection for ICI treatment should not be impacted by prior exposure to BCG. Further clinical and molecular biomarker exploration is needed to refine patient selection for ICI in aUC.[Table: see text]

The use of apple cider vinegar as a secondary treatment line with conventional diabetic treatment as a new medical hypothesis linking type 1 diabetes and type 2 diabetes

The diabetes as a disease has been reported for 3500 years. Although diagnostic and therapeutic approaches have continuously developed, no definitive therapeutic approaches have so far been reached. Diabetes is not a single disease; it interferes with various systems in the body including nervous system and cardiovascular system. The therapeutic lines for type 1 diabetes start with insulin and will need another treatment such as metformin. On the other hand, type 2 diabetes treatment strategies start with metformin and there will be a need for another treatment, insulin according to the disease progression. At certain point, both types of diabetes are treated applying the same strategies. In this study, we followed another strategy by applying the use of apple cider vinegar in patient with type 1 diabetes, and patient with type 2 diabetes following getting each meal. The results showed that glucose levels were within reference range after five days. Taken together, the use of apple cider vinegar as a secondary treatment line with conventional diabetic treatment is promising and needs to be further investigated