March 2022: The Food and Drug Administration has approved rituximab (Rituxan, Genentech, Inc.) in conjunction with chemotherapy for CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukaemia in children aged 6 months to 18 years (B-AL).
Inter-B-NHL Ritux 2010 (NCT01516580) was a global multicenter, open-label, randomised (1:1) trial of patients aged 6 months and older with previously untreated, advanced stage, CD20-positive DLBCL/BL/BLL/B-AL, with advanced stage defined as Stage III with elevated lactose dehydrogenase (LDH) level (LDH greater than twice the institutional upper limit of normal values) or stage IV B-cell NHL or Lymphome Malin B (LMB) chemotherapy (corticosteroids, vincristine, cyclophosphamide, high-dose methotrexate, cytarabine, doxorubicin, etoposide, and triple drug [methotrexate/cytarabine/corticosteroid] intrathecal therapy) was given to patients either alone or in combination with rituximab or non-U.S. According to the LMB scheme, licenced rituximab was administered as six infusions of rituximab IV at a dose of 375 mg/m2 (2 doses during each of the two induction sessions and one dose during each of the two consolidation courses).
EFS was defined as worsening disease, relapse, second malignancy, death from any reason, or non-response as shown by detection of live cells in residual after the second CYVE (Cytarabine [Aracytine, Ara-C], Veposide [VP16]) treatment, whichever came first. In 328 randomised patients with a median follow-up of 3.1 years, an interim effectiveness study at 53 percent information fraction was done. The LMB group had 28 EFS episodes, while the rituximab-LMB group had 10 (HR 0.32; 90 percent CI: 0.17, 0.58; p=0.0012). There were 20 deaths in the LMB chemotherapy arm at the time of the interim analysis, compared to 8 deaths in the rituximab plus LMB chemotherapy arm, for an overall survival HR of 0.36. (95 percent CI: 0.16, 0.81). Overall survival (OS) was not subjected to a rigorous statistical test, and the result is regarded descriptive. After the interim analysis, the randomization was stopped, and an additional 122 patients were given rituximab plus LMB treatment and contributed to the safety analysis.
febrile neutropenia, stomatitis, enteritis, sepsis, elevated alanine aminotransferase, and hypokalemia were the most common adverse events (grade 3 or higher, >15 percent) in paediatric patients treated with rituximab plus chemotherapy. Sepsis, stomatitis, and enteritis were among the grade 3 or higher adverse responses that occurred more frequently in the rituximab plus LMB treatment arm compared to LMB chemotherapy. In both the rituximab plus LMB chemotherapy and LMB chemotherapy arms, fatal adverse events occurred in 2% of patients.
Rituximab is given as an intravenous infusion in combination with systemic LMB treatment at a dose of 375 mg/m2. Six infusions of rituximab are given in total, two doses during each of the induction courses, COPDAM1 [cyclophosphamide, Oncovin (vincristine), prednisolone, Adriamycin (doxorubicin), methotrexate] and COPDAM2, and one dose each of the two consolidation courses, CYM (Cytarabine [Aracytine, Ara-C], methotrexate
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
