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.

The limited use of autologous hematopoietic stem cell transplant for fit older patients with multiple myeloma in India: a retrospective analysis.

BACKGROUND: Multiple myeloma (MM) predominantly affects older patients; many of whom do not undergo autologous hematopoietic stem cell transplant (AHSCT) despite the associated survival benefits. This study was conceived to investigate the patterns of AHSCT among MM patients with due regard to their age and standardized fitness assessments. METHODS: Fitness scores as per the hematopoietic stem cell transplant-comorbidity index (HSCT-CI) and risk scores as per the revised-myeloma comorbidity index (R-MCI) of MM patients treated between January 2017 and December 2019 were analyzed to assess fitness for AHSCT. Proportions of patients who underwent AHSCT were calculated with regard to age and fitness for AHSCT. RESULTS: Of the 81 eligible patient records with a median age of 62 years, the HSCT-CI classified 79.6% and 77.8% of patients aged ≤65 years and >65 years as AHSCT eligible (p 1). Using the R-MCI, 96.3% and 81.5% of patients aged ≤65 years and >65 years, respectively, were classified as eligible for AHSCT (p 0.0381). Overall, patients aged ≤65 years underwent AHSCT with a greater frequency compared to those aged >65years (38.9 vs. 14.8%, p 0.0402). Irrespective of the age group, there was a statistically significant difference (p 0.0167) in terms of survival which favored those who underwent AHSCT. CONCLUSIONS: Both the HSCT-CI and the R-MCI revealed that nearly 80% of patients aged >65 years were fit enough to receive AHSCT. However, far fewer patients of this age group underwent AHSCT. We propose that the routine inclusion of objective fitness assessment could ensure that fit older patients undergo AHSCT and thus do not miss out on the benefits of the same.

Impact of Molecular Predictors on the Response Rates in Head and Neck Cancer Patients - an Observational Study.

Squamous cell carcinoma of head and neck region account for more than 25 % of male and more than 10 % of female cancers in India (1). Head and neck cancer treatment includes a multidisciplinary approach involving all specialties. Concurrent chemo-radiation is the standard of care in most of the subsites (2). Inspite of the multi-disciplinary approach, a plateau has been reached in terms of results with 5 year survival of locally advanced disease of around 30 % (3). In order to improve outcomes, there has been considerable interest in molecular profiling of head and neck cancers 4-10. However there is still significant paucity in terms of Indian data, hence the need for the study. The objectives are to assess the HPV-p16, EGFR and p53 status, to correlate HPV-p16, EGFR and p53 status with the response rates, to correlate HPV-p16,EGFR and p53 status with other factors like age, sex, tobacco use. Twenty five consecutive cases of histopathologically proven head and neck cancers were accrued. All patients were treated with external radiation to a dose of 66Gy in 33 fractions along with concurrent weekly cisplatin chemotherapy at a dose of 40mg/sqm. HPV-p16, EGFR and p53 mutation analysis was done on paraffin embedded histopathological blocks. PCR technique used for HPV-p16, EGFR and p53 status detection. Response assessment was done based on RECIST criteria. Correlation of HPV, EGFR and p53 status on response was done. The EGFR positivity rate was 84 %, the p53 positivity rate was 76 % and the HPV p-16 positivity rate was 28 %. Out of 25 patients, 13(52%) had complete response, 7(28 %) had partial response, 3(12 %) had stable disease and 2(8 %) had progressive disease. On correlation of molecular profile with response, there was no statistical significance between EGFR status and response (p 0.5) or HPV-p16 and response (p 0.8). However, p53 positivity was approaching significance with respect to good response (p 0.07).

Variant Philadelphia translocations in chronic myeloid leukemia: A report of five cases.

The t (9;22)(q34;q11) translocation is found in about 90% of the chronic myeloid leukemia patients. About 5-10% of these patients have complex variant translocations involving a third chromosome in addition to chromosomes 9 and 22. We describe five male patients in the chronic myeloid leukemia-chronic phase, with rare variant Philadelphia translocations. All of them had the BCR-ABL fusion gene and responded well to treatment with imatinib mesylate. All the patients are on regular follow-up.

Voriconazole-induced psychosis in a case of acute myeloid leukemia with febrile neutropenia.

Voriconazole-induced psychosis is a rare side effect. It is important that clinicians are made aware of voriconazole-induced potential psychosis. We report a case of voriconazole-induced psychosis that responded to haloperidol.

Management of Hodgkin's lymphoma with midbrain involvement: A case report and review of literature.

Introduction Primary central nervous system (CNS) involvement of Hodgkin's lymphoma is very uncommon. There are only a few previous reports of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS concurrently with systemic disease. Case presentation A 12-year-old boy with a history of painless left inguinal swelling and acute diplopia. There was an intensely enhancing lesion in the right midbrain on magnetic resonance imaging. The patient was diagnosed with stage IV Hodgkin's lymphoma of nodular lymphocyte predominance type by routine microscopy and immunohistochemistry of left inguinal lymph node biopsy with computed tomography-assisted staging. It was planned to treat him with six cycles of chemotherapy with intrathecal methotrexate, followed by radiotherapy to the CNS lesions. After two cycles of chemotherapy, the patient entered complete remission of all lesions including the CNS lesion documented by the positron emission tomography scan. Conclusion We are describing the course of this rare presentation of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS and clinical challenge in its diagnosis and management of this case.

Relapsed Hodgkin's Lymphoma Presenting with Isolated Ulcerative Lesion on Base of Tongue.

INTRODUCTION: Primary extra nodal involvement of Hodgkin's lymphoma is very uncommon and previous reports of Hodgkin's lymphoma involving the base of tongue as isolated lesion in relapsed disease are few. CASE PRESENTATION: A 79-years male patient who has diagnosed and treated for stage IV Nodular sclerosis Hodgkin lymphoma 2 years back, now presented with isolated ulcerative lesion in base of tongue which was metabolically active on positron emission tomography scan, suspicious of recurrent disease and was confirmed by routine microscopy and immunohistochemistry of tissue biopsy. CONCLUSION: Extra nodal relapse at base of tongue was an uncommon clinical scenario in natural history of Hodgkin's lymphoma, which can present as an unexpected challenge for diagnosis and management. So we should be aware of this uncommon but unique presentation of Hodgkin's lymphoma.

Acute interstitial lung disease in a patient with anaplastic lymphoma kinase-positive non-small-cell lung cancer after crizotinib therapy.

Crizotinib, an orally active multi-targeted small-molecule anaplastic lymphoma kinase (ALK) inhibitor, is an effective treatment modality for advanced ALK-positive non-small-cell lung cancer (NSCLC). Most drug-related adverse events are mild to moderate; however, some patients may develop acute interstitial lung disease (ILD) which is sometimes fatal. We present a case of crizotinib-associated ILD in a 47-year-old woman treated with crizotinib for metastatic adenocarcinoma of the lung. The patient presented with acute breathlessness and hypoxaemia in the second month of crizotinib therapy; radiological and histopathological work-up was suggestive of acute interstitial pneumonia. The patient improved clinically with corticosteroid therapy and was successfully re-challenged with crizotinib. In conclusion, while treating NSCLC patients with crizotinib, it is important to promptly investigate and treat any new-onset respiratory symptoms, as the latter could represent an adverse effect related to therapy. Prompt discontinuation of the offending drug and initiation of corticosteroid therapy may prevent adverse outcomes.

Epidermal growth factor receptor inhibitors related trichomegaly of Eyelashes.

Advances in understanding of the mechanisms involved in oncogenesis have led to the development of targeted therapies such as epidermal growth factor receptor inhibitors (EGFRIs), targeting a variety of molecular structures and able to inhibit aberrantly activated oncogenic pathways. Their use made treatment more tolerable with significant reduction of systemic adverse effects. However, EGFRIs are associated with toxicities affecting the skin and adnexal structures that affect the majority of treated patients. Trichomegaly of eyelashes is a unique side-effect, seen in prolonged treatment with EGFRI. It is essential to be familiar with this adverse effect, its potential complications, long-term sequelae, and available effective treatment strategy in order to appropriately manage these patients.

Technique of intraperitoneal chemotherapy using veress needle in patients with ovarian cancer.

Adjuvant intraperitoneal chemotherapy in ovarian cancer has shown improved survival but limited by catheter-related complications. We present a technique of Veress needle use for intraperitoneal instillation of chemotherapy for 220 procedures in 43 patients with minimal adverse effects all managed conservatively. Our unique technique of paclitaxel instillation is described.

Rituximab-induced subacute interstitial pneumonitis: a case report and review of literature.

Rituximab is a chimeric anti-CD20 monoclonal antibody used to treat CD20+ non-Hodgkin's lymphoma (NHL). Some pulmonary adverse reactions such as cough, rhinitis, bronchospasm and dyspnea are relatively common. Severe respiratory conditions like cryptogenic organizing pneumonia, interstitial pneumonitis have rarely been reported. We present a case of interstitial pneumonitis in a patient who was treated with R-CHOP for extranodal NHL. He responded to the steroids.

Membranoproliferative glomerulonephritis secondary to chronic myeloid leukemia.

The nephrotic syndrome (NS) is a well documented complication of hematological malignancies. However, chronic myeloid leukemia (CML) is rarely complicated by the NS, and it occurs usually after allogenic stem cell transplantation or interferon alpha therapy for CML. The NS as a complication of untreated CML is also rare. We report a 31-year-old patient who presented with features of The NS. He was diagnosed to have CML one year ago and was on irregular treatment with imatinib mesylate. The renal biopsy and immunofluorescence revealed membrano-proliferative glomerulonephritis type I. The patient was retreated with imatinib mesylate and the NS resolved gradually over three months. This maybe the third case in literature of membrano-proliferative glomerulonephritis associated with CML.

Embryonal rhabdomyosarcoma of the chest wall: a case report and review of the literature.

Embryonal rhabdomyosarcoma is a soft-tissue sarcoma which has a predilection for the head and neck area, genitourinary tract and the extremities. We report a rare case of embryonal rhabdomyosarcoma of the chest wall in an 8-year-old girl, presenting as a destructive tumor in the rib and clinically and radiologically mimicking Ewing's sarcoma. Histopathological examination showed a small round cell tumor. Immunohistochemically, the positivity for muscle markers desmin and myogenin in the tumor cells proved to be useful for making a definitive diagnosis of embryonal rhabdomyosarcoma. Cytogenetic analysis revealed a high level of aneuploidy in the tumor cells, with double-minutes and additional chromosomal structural aberrations. The patient is responding well to chemotherapy.