Daratumumab in Indian patients with relapsed and refractory multiple myeloma: a prospective, multicenter, phase IV study.

Aim: To assess the safety and effectiveness of daratumumab monotherapy in Indian patients with relapsed/refractory multiple myeloma. Methods: In this prospective, multicenter, phase IV study, patients (aged ≥18 years) received intravenous daratumumab (16 mg/kg) in six cycles. Safety was the primary end point. Results: Of the 139 patients included, 121 (87.1%) experienced ≥1 treatment-emergent adverse events (TEAEs; 53 [38.1%] drug-related), 32 (23%) had ≥1 serious TEAEs (five [3.6%] drug-related) and 16 (11.5%) deaths were reported (one death [0.7%] was drug-related). Overall response rate was 26.3%; 62.7% of patients had stable disease. Median time to first response and median progression-free survival were 5.2 and 5.9 months, respectively. Functional status and well-being were improved. Conclusion: Daratumumab showed an acceptable and expected safety profile with consistent efficacy, providing a novel therapeutic option for relapsed/refractory multiple myeloma management in India.

Daratumumab is a monoclonal antibody approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). This study evaluated the outcome of daratumumab single therapy in Indian patients who were not cured with other drugs used for the same disease. 139 adult patients were included in this study from 15 institutes across India. Daratumumab (16 mg/kg) was diluted with 500 or 1000 ml of saline solution and given slowly through the intravenous route 16-times within 6 months. The study examined whether the safety profile and benefits of daratumumab reported in Indian patients were similar to those reported in the RRMM populations of other countries. The study found that most of the adverse events were not severe and could be easily treated by the study physician. 16 patients died (one might have been due to daratumumab treatment). Daratumumab treatment provided life support and recovery benefits to many patients. Daratumumab single therapy provides an appropriate and acceptable safety profile with no new adverse events and consistent benefits in RRMM patients. Clinical Trial Registration: NCT03768960 (ClinicalTrials.gov), CTRI/2019/06/019546.

Role of daratumumab in the frontline management of multiple myeloma: a narrative review.

INTRODUCTION: The prevalence of multiple myeloma (MM) has gradually increased over the last few decades in India due to growing population, better disease awareness, and improved diagnostic procedures. Despite such advances, MM remains an incurable and relapsing disease due to its heterogeneity and genomic instability. With the inclusion of monoclonal antibodies, especially daratumumab in the frontline regimen, the management landscape of MM has improved significantly resulting in better disease control and patient outcomes. AREAS COVERED: This review aims to provide an in-depth summary of efficacy and safety of frontline daratumumab therapy in treatment of MM including patients with high-risk cytogenetic profile. EXPERT OPINION: Based on the review of literature, daratumumab in frontline therapy has demonstrated improved efficacy in terms of reduction in disease progression or death, and superior minimal residual disease (MRD)-negativity rates with an acceptable safety profile in patients with newly diagnosed MM (NDMM) including patients with high-risk cytogenetic profile. Daratumumab alone or in combination with other drugs has shown similar clinical outcomes in patients with relapsed/refractory MM. Hence, daratumumab can be used upfront in patients with MM.

Safety profile of G-CSF in chemotherapy-induced neutropenia: A prospective observational study in Eastern India.

Background: Granulocyte-colony stimulating factor (G-CSF) is used in cancer patients to treat chemotherapy-induced neutropenia (CIN). However, G-CSF poses few risks. Despite the regular use of G-CSF in CIN management, there is a paucity of published data on its safety profile in the management of CIN in India. Hence, the present study was designed to demonstrate the safety profile of G-CSF in patients with CIN. Methods: A prospective observational study was conducted over a period of 5 months enrolling 100 cancer patients aged from 18 years to 70 years. Patients with a diagnosis of CIN who received G-CSF were included. Patients were followed up for 15 days. Adverse events (AEs) were graded according to US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The system organ class and preferred term of Medical Dictionary for Regulatory Activities (MedDRA) were used for reporting the AEs. Causality assessment was done by using the WHO-Uppsala Monitoring Centre scale. Results: The most frequently reported AEs were musculoskeletal and connective tissue disorders which included bone pain, myalgia, arthralgia, and pain in the extremity. Other AEs reported were general disorders and administration site conditions, and gastrointestinal disorders. The highest grade of toxicity reported was of grade 3 among all AEs. The majority of AEs had a "probable" type of causality relationship with G-CSF. Conclusion: ">G-CSF has a safety profile consistent with previous G-CSF studies.

Pretomanid: The latest USFDA-approved anti-tuberculosis drug.

Pretomanid is a nitroimidazooxazine drug which inhibits synthesis of mycolic acid. This leads to defective cell wall formation, ultimately causing bacterial cell death. It is active against both replicating and non-replicating M. tuberculosis. Following promising result in a phase III trial, pretomanid was approved by United States Food and Drug Administration in August 2019. This orally active drug has been approved as part of a combination regimen of bedaquiline, pretomanid and linezolid (BPaL regimen) to treat adults with pulmonary extensive drug resistant tuberculosis (TB) or treatment-intolerant or non-responsive multidrug resistant TB. Peripheral neuropathy and increased liver enzymes are some of the reported adverse events associated with pretomanid. However, more studies are required to confirm the role of pretomanid in paediatric, geriatric and HIV co-infection cases.

Efficacy and safety of modafinil versus dexamethasone in cancer-related fatigue: a prospective randomized controlled study.

The aim of this study was to compare the efficacy and safety of modafinil and dexamethasone in the management of cancer-related fatigue and their effects on quality of life (QoL). A prospective randomized controlled study was conducted, enrolling 80 cancer patients experiencing moderate or severe fatigue following at least three cycles of chemotherapy or a course of palliative/curative radiotherapy. Patients received either oral modafinil 100 mg or dexamethasone 4 mg daily for 14 days. Levels of fatigue, QoL and symptom severity were compared after 14-21 days. Both drugs were efficacious and safe in the management of fatigue and QoL. However, modafinil performed marginally better. Although modafinil demonstrated marginal superiority, both modafinil and dexamethasone can improve fatigue and QoL in cancer patients. Clinical trials registry of India: CTRI/2018/05/014046 (www.ctri.nic.in).

Lay abstract Cancer-related fatigue is a common and nagging problem that needs best evidence-based management. Modafinil, a brain stimulant, and dexamethasone, a corticosteroid, have been shown in separate studies to provide benefit, but there are little data regarding which one is superior. The present study compared modafinil with dexamethasone in a randomized controlled trial. Modafinil was found to be marginally superior in treating cancer-related fatigue and several domains of quality of life, though dexamethasone also demonstrated significant improvement of fatigue. This study provides a valuable guide for future larger studies for implementation of the findings in the form of better patient care.