Multiple Myeloma: Risk Adapted Use of Plerixafor for Stem Cell Mobilization Prior to Autologous Stem Cell Transplantation is Effective and Cost Efficient.

BACKGROUND: We used plerixafor in 'a risk adapted approach' for stem cell mobilization for multiple myeloma (MM) patients prior to autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: Between January, 2017 and December, 2019 105 consecutive patients of MM were recruited (Study Cohort). Patients received inj G-CSF 10 µg/kg in 2 divided doses for 5 days. Day 4 peripheral blood (PB) CD34+ count was used as a guide; if count was < 20 cells/µl, patients received plerixafor. For those with ≥ 20 cells/µl apheresis was commenced on day 5. We compared their outcome with 156 MM patients transplanted between 2012 and 2016 with G-CSF mobilized PB stem cells (Control Cohort). Primary end point was to collect ≥2.0  ×  106 CD34+ cells/kg (minimal harvest). Secondary end points were: no of apheresis sessions, percentage of patients with optimal stem cell harvest (≥4.0  ×  106 CD34+ cells/kg) and cost analysis. An intent to treat analysis was done. RESULT: 96.2% of patients achieved ≥ 2.0  ×  106 CD34+ cells/kg in the study cohort vs. 87.2% in the control cohort, P < .01. Mean apheresis sessions were 1.5 vs. 1.7 respectively, P < .014 . Optimal stem cell harvest was 29.5% vs. 16%,P = .23. Days for neutrophil engraftment (P < 0.025) and for IV antibiotics (P < .0017) were favorable for the study cohort. Incremental cost effectiveness ratio was $ 15.80/- and $ 10.56/- per 1% increase to achieve a minimal and optimal harvest. CONCLUSION: Plerixafor in this risk adapted strategy resulted in successful mobilization, decreased time to engraftment and was cost effective.

Safety and Efficacy of Modified FOLFIRINOX in Unresectable or Metastatic Gallbladder Cancer: A Phase II Pilot Study.

PURPOSE: For unresectable gallbladder cancer (GBC), gemcitabine and platinum is standard combination; however, outcome is poor. We conducted this study to find feasibility of modified flourouracil, oxaliplatin, and irinotecan in this group. MATERIALS AND METHODS: We conducted a prospective, phase II single-arm pilot study. Inclusion criteria were histologically proven GBC and Eastern Cooperative Oncology Group 0-1. Primary end points were overall response rates and overall survival. The following treatment was given: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and irinotecan 150 mg/m2, all once on day 1, fluorouracil 2,400 mg/m2 continuous intra-venous infusion over 46 hours repeated every 2 weeks, and maximum 12 doses, with primary granulocyte colony-stimulating factor prophylaxis. RESULTS: Between February 2019 and July 2020, 29 patients with unresectable GBC were enrolled. The median age was 52 years, and 18 were females. The Eastern Cooperative Oncology Group was 0 in 4. Five had bilirubin > normal, and 15 each had high serum alkaline phosphatase and carbohydrate antigen 19-9. Twenty-five patients had stage IV disease, and remaining unresectable locally advanced disease. A median of 8.5 cycles was given, and 11 completed treatment. Nine stopped chemotherapy because of progression, and one because of toxicity, and treatment is ongoing in three. Twenty-two required dose reduction. A treatment delay of 1-2 weeks was seen in 25 patients. Best response was complete response 1, partial response 13 (overall response rate 48.2%), and stable disease 9. Four patients with metastatic disease underwent R0 resection. As on cutoff date, nine are surviving (three without disease). Eighteen died of PD, and in two, cause was unknown. There was no toxic death. The median overall survival and progression-free survival were 309 and 252 days, respectively. Twenty-three patients experienced grade III or IV toxicity, and common were diarrhea (13), vomiting (12), and anemia (7). CONCLUSION: First-line modified flourouracil, oxaliplatin, and irinotecan is feasible in unresectable GBC with encouraging responses. Toxicities are higher but manageable. Higher response rates make this an option to explore in borderline resectable cases.

Allogeneic hematopoietic stem cell transplant in pediatric acute myeloid leukemia: Lessons learnt from a tertiary care center in India.

There is paucity of data on outcomes of MSD-HSCT in children with relapsed or high-risk AML from developing countries, which have unique challenges including adverse host factors and resource constraints. We retrospectively reviewed records of children (age ≤ 18 years) who underwent MSD-HSCT for AML at our center from 2009 to 2019 to evaluate clinical outcome and its predictors using Cox proportional hazards model. There were 46 children (36 boys and 10 girls) with mean age 10.7 ± 4.8 years. Indication for HSCT was relapsed AML in CR2 (n = 37), primary refractory (n = 3), or relapsed refractory disease (n = 3); high-risk (n = 1) or secondary (n = 2) AML in CR1. Five-year EFS and OS were 33.3 ± 7.2% and 36.3 ± 7.6%, respectively. On multivariate analysis, CR1 duration less than 12 months, presence of active disease at transplant, and use of bone marrow stem cell graft were associated with poorer EFS and OS. There was one (2.2%) TRM, while disease relapse occurred in 20/40 patients who underwent HSCT in remission. Though the 5-year EFS and OS were inferior to results reported from high-income countries, relapse (and not TRM) was the major cause of treatment failure. A well-sustained CR1, achievement of disease remission, and use of peripheral blood allograft seem imperative to a successful transplant. Targeted therapy along with HSCT may be the option for those with early relapse.

Clinical predictors of response to EGFR-tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: A real-world multicentric cohort analysis from India.

BACKGROUND: The development of various targeted therapies against Epidermal Growth Factor Receptor (EGFR) has been a major step in therapeutic advancements in lung cancer. However, the response to tyrosine kinase inhibitors (TKI) therapy in a real-world setting has not been well elucidated. METHODS: As part of a retrospective analysis, patients with EGFR mutated non-small cell lung cancer at 4 tertiary care Institutions in North India between December 2007 and August 2018 were evaluated. The overall response rate, disease control rate, progression-free survival (PFS) and factors affecting PFS were analyzed. RESULTS: A total of 483 patients were included, including 52.4% males, with mean (±SD) age of 56.7 (±12.4) years. Majority (63.8%) had good performance status (Eastern Cooperative Oncology Group 0 or 1) and 77.4% were nonsmokers. Among the EGFR mutations, exon 19 deletion was the most common mutation detected (68.1%), followed by L858R mutation in exon 21 (26.9%). Extra-thoracic metastasis was present in 69.5% patients and majority of them had ≤ 2 metastatic sites (85.1%). TKIs were used as the first-line therapy in 64.8% patients, and gefitinib was the most frequently used TKI (67.3%), followed by erlotinib (26.7%). The overall response rate and disease control rate were 65.9% and 90.7% respectively. The median PFS was 9.3 months and brain was the exclusive site of progression in 18.0% patients. On univariate analysis, the factors that significantly affected PFS were, the number of metastatic sites and the type of EGFR mutation. On multivariate analysis, the number of metastatic sites was the only factor that affected the PFS [HR (95% CI): 2.5 (1.7-3.6); Pvalue <0.001]. Skin toxicity was the most common adverse event (32.3%), followed by involvement of the gastro-intestinal tract (22.5%). CONCLUSION: In this one of the largest multicentric Indian study of treatment outcomes in EGFR-mutated non-small cell lung cancer in a real-world setting, we found that increased tumor burden (number of metastatic sites > 2) was the only significant factor associated with a worse PFS.

Real world experience of treatment and outcome in ALK-rearranged metastatic nonsmall cell lung cancer: A multicenter study from India.

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearranged metastatic non-small cell lung cancer (NSCLC) comprises 5%-7% of all lung cancer and carries a good prognosis with available ALK-inhibitors. Majority of registration trials in ALK-inhibitors did not include Indian patients. Hence, this study was planned to analyze the outcome of Indian patients treated with ALK-inhibitors and associated challenges. METHODS: This is a multi-center study in 5 major tertiary care cancer centers across India treating ALK-rearranged NSCLC patients from April 2013 to April 2019. ALK rearrangement was determined by Ventana immunohistochemistry with D5F3 clone and/or by break-apart FISH. Patients treated with ALK-inhibitors in any lines of treatment were included in this study. Patients were evaluated for clinicopathologic features, patterns of ALK-inhibitors use and outcome. Progression free-survival (PFS) and overall survival (OS) were calculated and data were censored on April 30, 2019. RESULTS: A total of 274 patients were studied, out of which 250 patients received ALK inhibitor and were analyzed further for outcome. The median age was 50 years (range: 24-82) and male to female ratio of 1.17:1. ALK was evaluated by immunohistochemistry in majority of patients (97%), 3 patients by FISH and 3 more patients were evaluated by both methods. Sixty-five percent (n = 162) of the patients received ALK-inhibitor as first line therapy, 51 patients received ALK-inhibitor as switch maintenance therapy after initial chemotherapy. Crizotinib and Ceritinib were used in 88% and 12%, respectively. One patient received Alectinib. Forty-one percent of patients had CNS progression. After median follow up of 27 months (1-72 months), the median OS was 24.7 months with OS rate of 72%, 51%, and 18% at 1, 2, and 4-years respectively. Median OS was 21.2, 26, and 38 months in the first line ALK-inhibitors use (n = 162), switch maintenance group (n = 51) and second line ALK-inhibitors use (postchemotherapy progression) (n = 33), respectively. No baseline variable predicted PFS. Presence of brain metastasis (P = 0.039) and first line ALK-inhibitors use (P = 0.032) emerged as poor prognostic factor for OS on multivariate analysis. PFS rate was 70%, 47%, and 31% at 6, 12, and 18 months respectively. CONCLUSION: This is one of the largest real-world data on outcome of ALK inhibitors in ALK-rearranged NSCLC from Asia. In absence of second line ALK inhibitor, initial chemotherapy followed by ALK-inhibitors (switch maintenance) had better outcome. This fact may be studied in individual patient data meta-analysis. Poor performance status and brain metastases at presentation are poor prognostic factors for overall survival. Second-line ALK inhibitor use crucial for better outcome and access to clinical trials are much needed in Indian patients.