COVID-19 Vaccine Uptake in Patients with Multiple Myeloma and AL Amyloidosis: A Cross-Sectional Observational Study from India.

COVID-19 vaccine uptake has been comparable, if not higher, in LMICs (Low- and Middle-Income Countries) than in developed nations. Patients with plasma cell disorders are at a higher risk for developing COVID-19 related morbidity and mortality due to impaired immune responses. We report the outcome of active counselling for COVID-19 vaccines in patients with multiple myeloma (MM) and AL amyloidosis and the reasons for hesitancy in those unvaccinated. This was a cross-sectional, single-centre, observational study enrolling patients who visited the hospital between January 1, 2021 and June 30, 2021. Patients with MM and AL amyloidosis at diagnosis or follow-up were actively counselled by treating oncologists regarding the available COVID-19 vaccines (Covishield and Covaxin) during clinic visits or hospital admission. In the subsequent hospital visits, vaccination details were collected and verified. A structured interview schedule was administered to unvaccinated patients to identify the reasons behind vaccine hesitancy. Association of vaccine acceptance with socio-economic parameters and other disease parameters was studied using Chi-square test. Out of 195 patients, 178 (91%) were included in the study; 17 were lost to follow-up. At least a single dose of vaccine was administered in 86%. 79% received Covishield, whereas 21% received Covaxin. 67% received both vaccine doses. Vaccine-related side effects were mild and no vaccine-related thrombotic events were seen. Three patients died due to COVID-19-related causes, of which two were unvaccinated. The reasons for hesitancy in the 24 unvaccinated patients included: 9-poor general health conditions, 8-lack of advice from doctors, 2-fear of side effects, and 2-unavailability of vaccine delivery centres nearby. In comparison to the other studies, we report a higher vaccine uptake which can be attributed to targeted counselling by the treating oncologist and the universal free vaccination programme that is familiar to all Indians.

Relevance of flow cytometric categorization and end-of-induction measurable residual disease assessment in pediatric and adult T-lymphoblastic leukemia patients.

Background: T-lymphoblastic leukemia (T-ALL) patients expressing myeloid/stem cell antigens are classified as early T-cell precursor lymphoblastic leukemia (ETP-ALL) or near-ETP-ALL. Methods: Clinico-laboratory profiles, flow cytometric end-of-induction measurable residual disease (EOI-MRD), and survival of treatment naïve T-ALL patients were analyzed according to their immunophenotypic subtypes. Results: Among 81 consecutive T-ALL patients diagnosed, 21% (N=17) were ETP-ALL and 19% (N=15) were near-ETP-ALL. EOI-MRD was detectable in 39% of the 59 samples tested (31.6% of pediatric samples and 52.4% of adult samples). The frequency of EOI-MRD positivity was significantly higher among ETP-ALL (75%, P=0.001) and near-ETP-ALL (71%, P=0.009) patients compared to that in conventional-T-ALL (con-T-ALL) patients (22.5%). CD8 (P=0.046) and CD38 (P=0.046) expressions were significantly upregulated in the EOI blasts of con-T-ALL and ETP-ALL samples, respectively. The 2-year rates of overall (OS), relapse-free (RFS), and event-free survival (EFS) among the T-ALL patients (pediatric vs. adult) was 79.5% vs. 39.8% (P<0.001), 84.3% vs. 60.4% (P=0.026), and 80.3% vs. 38% (P<0.001), respectively. Univariate analysis revealed that 2-year EFS and RFS of pediatric T-ALL patients was independent of T-ALL subtype and was influenced only by EOI-MRD status. However, 2-year OS, RFS, and EFS among adult T-ALL patients were EOI-MRD independent and influenced only by the near-ETP-ALL phenotype. Conclusion: Two-year survival among pediatric and adult T-ALL patients is attributed to EOI-MRD status and near-ETP-ALL phenotype, respectively.

Therapeutic Outcomes in High-Grade B-Cell Lymphoma, NOS: Retrospective Analysis.

The nomenclature high-grade non-Hodgkin's lymphoma was repurposed in the World Health Organization (WHO) 2016 update as high-grade B cell lymphoma (HGBL). However, among the HGBL entities HGBL, not otherwise specified (NOS) remains a poorly described entity with a lack of literature regarding its treatment and prognosis. The baseline characteristics, treatment, and outcome of HGBL, NOS cases were analyzed. Thirty HGBL, NOS patients were diagnosed between January 2017 and December 2019. Their median age was 49.3 years, and 30% had advanced IPI. The majority received R-CHOP chemotherapy, while five patients received dose-adjusted R-EPOCH. At a median follow-up of 15 months, nine patients had disease progression or relapse. EFS and OS were 22 months (12.1-31.9 months) and 37 months (29.4-44.0 months) respectively. Only NCCN-IPI ≤ 2 showed significant influence on the outcome. The results were similar to the outcomes previously reported. This study highlights the importance of NCCN-IPI in ascertaining the prognosis of HGBL, NOS. The literature review suggests that more intensive chemotherapy is ideal for HGBL, NOS. However, prospective trials are needed to prove whether the treatment of HGBL, NOS can be tailored based on NCCN-IPI.

Cost Effectiveness of Ribociclib and Palbociclib in the Second-Line Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer in Post-Menopausal Indian Women.

BACKGROUND: In this study, we evaluate the cost and outcomes of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus fulvestrant, fulvestrant alone, and conventional chemotherapy as the second-line therapy for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in India. METHODS: Using a Markov model, the clinical effectiveness of managing HR+, HER2- MBC in postmenopausal women with either a CDK4/6i (either ribociclib or palbociclib) and fulvestrant, fulvestrant alone, and chemotherapy (single-agent paclitaxel or capecitabine) was measured in terms of quality-adjusted life-years (QALYs). The costs were estimated from two different points of view: scenario I, as per the prevailing market prices of the drugs; and scenario II, as per the reimbursement rates set up by the publicly financed national health insurance scheme. Incremental cost per QALY gained with a given treatment option was compared against the next best alternative and was assessed for cost effectiveness using a threshold of 1-time the per capita gross domestic product (GDP) in India from a societal perspective. RESULTS: In scenario I, an MBC patient was found to incur a lifetime cost of Indian Rupees (₹) 2.54 million ($34,644), ₹2.53 million ($34,496), ₹512,598 ($6,984), ₹326,026 ($4,442) and ₹237,115 ($3,230) for the ribociclib and palbociclib combination arms, fulvestrant monotherapy, single-agent paclitaxel and the single-agent capecitabine treatment arms, respectively. The lifetime cost for CDK4/6i (ribociclib and palbociclib) combination therapy, fulvestrant monotherapy, paclitaxel, and capecitabine arms was estimated to be ₹1.94 million ($26,459), ₹1.92 million ($26,220), ₹315,387 ($4,296), ₹187,392 ($2,553) and ₹153,263 ($2,088), respectively, in scenario II. The mean QALYs lived per MBC patient with CDK4/6i (either ribociclib or palbociclib) combination therapy, fulvestrant, paclitaxel and capecitabine were estimated to be 1.4, 1.0, 0.9 and 0.7, respectively. None of the treatment arms are cost effective at current prices and reimbursement rates at a threshold of 1-time the per capita GDP of India. However, a 78% reduction in the current market price or a 72% reduction in the reimbursement rate of fulvestrant in the government-funded insurance program will make it a cost-effective treatment option for HR+, HER2- MBC patients in India. CONCLUSION: CDK4/6i (ribociclib and palbociclib) therapy is not a cost-effective treatment option for MBC patients. A 72% reduction in the reimbursement rate for fulvestrant monotherapy will make it a cost-effective treatment option in the Indian context.

The continuing conundrum in oligometastatic breast carcinoma: A real-world data.

The optimal management in Oligometastatic (OM) breast carcinoma is not defined. OBJECTIVES: To identify the prognostic factors influencing OM and the effect of Locoregional treatment (LRT) on survival in OM. METHODOLOGY: Patients with ≤5 metastases and each with ≤ 5 cm size were defined as OM. Data of OM were extracted from the Institute Registry between 2012 and 2018. The impact of prognostic factors on survival was analysed by univariate and multivariate Cox regression. The Kaplan Meier survival curves were used to plot PFS and OS. RESULTS: There were 170 patients with OM. The median follow-up was 61 months. Median OS was 43.3 months. The median OS was 74 months in OMD vs 22.7 months in Oligorecurrent disease (ORD) with 5year OS rate of 55.3% vs 16.5% respectively. In the multivariate analyses of OMD both Ki67 ≤ 50% and hormone therapy (HT) showed significant favourable survival outcome. While premenopausal status and HT showed significant survival benefits in ORD. The worse survival outcome in ORD could be because of their aggressive biology and deficit in LRT compared to literature review. The prognostic factors were swayed by the uneven distribution of HR status, grade and Ki67. CONCLUSION: The survival of OM was influenced by OMD, Ki67 ≤ 50%, premenopausal status and HT. The lesser survival rates of OM in the long term suggest the need for curative LRT to metastatic sites and primary tumor. The potential role of HT and targeted therapy with or without LRT need to be assessed in future randomised trials.

Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell - lineage antigen expression: experience from a tertiary cancer care center

Abstract Introduction Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. Materials and methods This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. Results In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p = 0.010) disease with frequent ETV6-RUNX1 fusion (p = 0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p = 0.001), especially for the frequent presence of BCR-ABL1 fusion (p = 0.004) and KMT2A rearrangement (p = 0.045). CD7-expressing B-ALL patients had inferior event-free survival (p = 0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p = 0.317). Conclusion In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.

Cost Effectiveness of Bevacizumab Plus Chemotherapy for the Treatment of Advanced and Metastatic Cervical Cancer in India-A Model-Based Economic Analysis.

PURPOSE: Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India. METHODS: Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty. RESULTS: Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy. CONCLUSION: Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.

Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell - lineage antigen expression: experience from a tertiary cancer care center.

INTRODUCTION: Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. MATERIALS AND METHODS: This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. RESULTS: In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p=0.010) disease with frequent ETV6-RUNX1 fusion (p=0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p=0.001), especially for the frequent presence of BCR-ABL1 fusion (p=0.004) and KMT2A rearrangement (p=0.045). CD7-expressing B-ALL patients had inferior event-free survival (p=0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p=0.317). CONCLUSION: In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.

Development of National Cancer Database for Cost and Quality of Life (CaDCQoL) in India: a protocol.

INTRODUCTION: The rising economic burden of cancer on healthcare system and patients in India has led to the increased demand for evidence in order to inform policy decisions such as drug price regulation, setting reimbursement package rates under publicly financed health insurance schemes and prioritising available resources to maximise value of investments in health. Economic evaluations are an integral component of this important evidence. Lack of existing evidence on healthcare costs and health-related quality of life (HRQOL) makes conducting economic evaluations a very challenging task. Therefore, it is imperative to develop a national database for health expenditure and HRQOL for cancer. METHODS AND ANALYSIS: The present study proposes to develop a National Cancer Database for Cost and Quality of Life (CaDCQoL) in India. The healthcare costs will be estimated using a patient perspective. A cross-sectional study will be conducted to assess the direct out-of-pocket expenditure (OOPE), indirect cost and HRQOL among cancer patients who will be recruited at seven leading cancer centres from six states in India. Mean OOPE and HRQOL scores will be estimated by cancer site, stage of disease and type of treatment. Economic impact of cancer care on household financial risk protection will be assessed by estimating prevalence of catastrophic health expenditures and impoverishment. The national database would serve as a unique open access data repository to derive estimates of cancer-related OOPE and HRQOL. These estimates would be useful in conducting future cost-effectiveness analyses of management strategies for value-based cancer care. ETHICS AND DISSEMINATION: Approval was granted by Institutional Ethics Committee vide letter no. PGI/IEC-03/2020-1565 of Post Graduate Institute of Medical Education and Research, Chandigarh, India. The study results will be published in peer-reviewed journals and presented to the policymakers at national level.

Cytogenetics and FISH negative cryptic acute promyelocytic leukemia with CD56 expression.

Acute promyelocytic leukemia (APL) is characterized by reciprocal translocation t(15;17)(q22;q21) and has a favorable prognosis upon immediate recognition and treatment. However, rare cases of APL show a cryptic insertion of retinoic acid receptor alpha (RARA) gene into promyelocytic leukemia (PML) gene which is negative both by fluorescence in situ hybridization (FISH) and conventional cytogenetics (CC). Morphology, cytochemistry and flow cytometry play a key role in early identification of such cases. Polymerase chain reaction (PCR) remains the most efficient diagnostic modality for detection of cryptic APL and other variants. It is important to identify these cases as they show beneficial response to retinoids and favourable prognosis. We herein present a rare case of cryptic APL negative by FISH and conventional cytogenetics but positive for PML-RARA by PCR.

COVID19 in children with cancer in low- and middle-income countries: Experience from a cancer center in Chennai, India.

Crowded outpatient clinics and common wards in many hospitals in low and middle-income countries predispose children, caregivers, and health care workers to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on the clinical features and outcomes of 15 children with cancer at our center who tested positive for SARS-CoV-2. Five out of 15 patients were symptomatic, and one patient required intensive care and respiratory support. All the patients in the study have recovered from the SARS-CoV-2 infection without any sequelae and have resumed their cancer treatment.

"Hairy Cell Leukemia (HCL): 'Real World' Outcome".

HCL is an uncommon B cell lympho-proliferative disorder with high remission rates. There is paucity of data on the long-term outcome of HCL from India. We retrospectively collected data from individual case records of patients with HCL who were treated in Cancer Institute, Chennai from January 2001 until January 2018. Sixteen patients were diagnosed with HCL and were treated with cladribine (81%), interferon (13%) and one patient received only best supportive care (6%). All the treated patients achieved complete response. More than half of the patients developed febrile neutropenia but there were no treatment related mortality. The 5-year DFS was 77% and 5-year OS was 80%. Relapse of disease was seen in 27%. HCL is a curable malignancy with high remission rates and survival comparable to patient treated in west.

Outcomes of Intensive Treatment of Adult Acute Myeloid Leukemia Patients: A Retrospective Study From a Single Centre.

BACKGROUND: Acute Myeloid Leukemia (AML) is a very aggressive cancer with difficult treatment and poor outcomes. The treatment of these patients is quite challenging due to various reasons including the need for extensive supportive care, and high cost of therapy. Reports on outcomes from India are few. METHODS: We analyzed 93 adult patients (≥ 18 years) with AML who were treated with curative intent between 2007 and 2014. Patients received daunorubicin at dose of 60-90 mg/m2 and cytarabine 100 mg/m2 during induction and consolidation with 3 courses of high dose cytarabine (1.5-3 g/m2per dose for 6 doses per cycle). Only 4 patients underwent consolidation allogenic stem cell transplantation in first remission (CR1). RESULTS: The median age was 37 (18-66) years; males: 52%. Conventional cytogenetics (N = 63) showed 23% (N = 15), 56% (N = 35), 27% (N = 13) in good, intermediate risk and poor risk category respectively. FLT3-ITD was positive in 12/33 (36%) and NPM mutation in 7/23 (30%). Daunorubicin dose was 60 mg/m2 in 75% (N = 70) and 90 mg/m2 in 25% (N = 23) patients. Induction mortality was 17% (16/93) [60 mg/m2:19% (13/70), and 90 mg/m2:13% (3/23); p = 0.39)]. Complete remission was achieved by 60% (56/93) [60 mg/m2:53% (37/70), and 90 mg/m2:83% (19/23); p = 0.09)]. The median overall survival was 9.2 months and the actuarial survival at 2 years was 30%. By univariate analysis, FLT3-ITD positivity, white cell counts higher than 100,000/mm3 at presentation, and use of lower dose of daunorubicin in induction were associated with poorer outcomes. CONCLUSIONS: Outcomes in adult AML are generally poor. Many patients with high risk disease don't receive allogenic transplantation in CR1. Increased availability of allogenic stem cell transplantation may help to improve outcomes.

Outcomes of Oral Metronomic Therapy in Patients with Lymphomas.

Oral Metronomic chemotherapy (OMC) is used in patients with lymphoma who may not tolerate intravenous chemotherapy or have refractory disease. It is cheaper, less toxic and easy to administer. Adult patients with lymphoma who received OMC (combination of cyclophosphamide, etoposide and prednisolone) were included in this retrospective analysis. Response assessment was clinical with limited use of radiology. Progression free and overall survival (PFS and OS) were calculated from the time of start of OMC until documentation of disease progression or death. Between 2007 and 2017, 149 patients were given OMC [median age: 62 years (19-87); 94 patients (63.1%) male]. Majority [112 patients (75.2%)] had stage III/IV disease. The most common subtype of lymphoma was diffuse large B cell lymphoma (40.9%). OMC was used at diagnosis in 41 patients (27.5%) and after relapse in 108 patients (72.5%). Overall response rates were 43.9 and 41.7% with clinical CR in 14 (34.1%) and 21 (19.4%) in patients given first line and later lines of OMC respectively. After a median follow up of 12 months (range 1-123 months), median PFS and OS were 10.5 (95% CI 8.6-12.5) and 18.8 (95% CI 12.1-25.5) months respectively. PFS and OS at 12 months were 47.6 and 64.2% respectively. Though OMC is used in many centers in India, there is scanty published information on its efficacy in lymphoma. In this analysis, we demonstrate its activity in a subset of patients with predominantly high-grade and advanced stage NHL. OMC is a useful option in frail patients and a small proportion can achieve deep and long lasting responses.