Real-world outcomes of diffuse large B-cell lymphoma in the biosimilar era.

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma (NHL). The clinical use of rituximab has improved the treatment response and survival of patients with DLBCL. The introduction of rituximab biosimilar into healthcare system has helped in providing a cost-effective treatment to B-cell lymphoid malignancies as standard of care and has improved access to patients worldwide. The aim of this study was to observe the real-world effectiveness and safety of Reditux™ and Ristova® in DLBCL patients. Methods: Observational study in adults with DLBCL receiving Reditux™ or Ristova® across 29 centers in India (2015-2022). Effectiveness and safety were assessed up to 2 years after first dose. Results: Out of 1,365 patients considered for analysis, 1,250 (91.6%) were treated with Reditux™ and 115 (8.42%) with Ristova®. At 2 years, progression-free survival (PFS) 69% [hazard ratio (HR), 1.16; 95% CI, 0.80-1.67], overall survival (OS) 78.7% (HR, 1.20; 95% CI, 0.78-1.86), response rates, quality of life (QoL), and overall safety in both the cohorts were comparable. The best overall response rate (BORR) at 6 months was comparable with no statistically significant differences between the Reditux™ and the Ristova® cohorts (89.2% vs. 94.3%). In multivariate analysis, BCL-2 and VAS were significant prognostic factors for PFS. Conclusion: Reditux™ and Ristova® were comparable in real-world setting. Clinical Trial Registration: ISRCTN registry, identifier (ISRCTN13301166).

Hematopoietic stem-cell transplantation in a zoo of multidrug-resistant organisms: Data from a cancer center in eastern India.

BACKGROUND: Infections by multidrug-resistant organisms (MDRO) are a major hurdle in hematopoietic stem-cell transplants (HSCTs). Conditioning regimens lead to mucosal barrier injury, which in-turn leads to transmigration of gut bacteria and sepsis. Pre-transplant stool and throat surveillance cultures can guide empirical antibiotic policy during the neutropenic period. In this paper, we document colonization with MDRO in pre-transplant surveillance cultures and the correlation with bloodstream infections in HSCT patients and analyze transplant outcomes with respect to these infections. METHODS: A single-center, retrospective study on HSCT was performed between January 2021 and December 2021. The incidence of bacterial infections, percentage of MDROs, correlation with pre-transplant stool/throat surveillance cultures, and their impact on overall 100-day and post-100-day to 6-month post-transplant survival were analyzed. RESULTS: Sixty-four patients were included in the study. Pre-transplant stool surveillance cultures were positive for MDRO in 85.9% of patients. Almost half (48.5%) of the isolates were positive for carbapenemase-producing genes (mainly New Delhi metallo-beta-lactamase-1 [NDM-1] and oxacillinase-48 [OXA-48]). Eighteen patients (18/64, 28%) had a positive blood culture for MDRO in the peri-engraftment neutropenic period. Correlation between surveillance and blood cultures was seen in 61% (11/18) of patients. All-cause mortality was 14.1% (9/64) and 25% (16/64) in patients at 100 days and 6 months post-HSCT, respectively. The 100-day and post-100-day all-cause mortality rates were higher in patients with Gram-negative MDRO bloodstream infections (p < .012 and <.008, respectively). CONCLUSION: MDRO infections can adversely affect HSCT outcomes. Pre-transplant stool and throat surveillance cultures may guide empirical antibiotic policy and lead to favorable transplant outcomes.

Bortezomib-based induction therapy followed by autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients: A single-center experience and review of Indian literature.

INTRODUCTION: High-dose chemotherapy with melphalan, followed by autologous hematopoietic stem cell transplantation (AHCT) remains the standard of care for consolidation therapy of fit patients with newly diagnosed multiple myeloma (NDMM), for more than 20 years now. MATERIAL AND METHODS: This is a retrospective study of NDMM patients who underwent AHCT at our center from 2011 to 2018. Data was undertaken using the hospital electronic medical records (EMR). RESULTS: Among transplant eligible patients (which were 764), 78 patients (10.2%) underwent AHCT. The predominant stage in the study cohort was International Scoring System (ISS)-III (55%), and IgG-kappa (44%) was the commonest subtype of multiple myeloma (MM). Light chain myeloma was found in 23.5% of patients. Pretransplant, 42%, 48%, and 10% patients were in more than very good partial response (>VGPR), very good partial response (VGPR), and partial response (PR), respectively. The median duration of follow-up was 57.2 months (range: 12.1-120.2 months). The entire cohort's 5-year overall survival (OS) and progression-free survival (PFS) were 89.1% and 41.8%, respectively. CONCLUSION: Bortezomib based triplet induction regimens were effective and well tolerated in this retrospective analysis of Indian patients. We observed that AHCT effectively achieves deep and durable remission in MM.

Should we adopt an automated de-centralized model of chimeric antigen receptor- T cells manufacturing for low-and middle-income countries? A real world perspective.

Autologous chimeric antigen receptor-T (CAR-T) cell therapy has proven itself as an effective therapeutic modality for cancers, especially hematological malignancies and is emerging as a potential candidate for solid organ cancers as well. However, the accessibility to treatment has been limited due to complexities and costs associated with manufacturing a genetically modified autologous product. The centralized model of CAR-T manufacturing which has emerged as the dominant model in developed nations does not seem well-suited to the needs and realities of the developing economies. In this context, we explore the relative advantages and disadvantages of the two models from a developing nation's perspective.

Indian Expert Opinion on Cancer Care during COVID-19 Pandemic.

Coronavirus pandemic has increased human disease burden, as well as economic distress globally. Being in an immunocompromised state, patients with cancer comprise an important at-risk population for novel coronavirus disease 2019 (COVID-19) infection. It is necessary to modify individualized clinical management for every cancer patient in the context of the ongoing COVID-19 pandemic. Simultaneously, additional safety precautions for the cancer care providers are mandatory. This review will provide general recommendations in the Indian context optimizing the same.

Outcomes of diffuse large B-cell lymphoma in elderly patients-real-world experience from a middle-income country setting.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the commonest subtype of lymphoma in the elderly and poses unique challenges in this group of patients. There is a need for more information on real-world outcomes across economic disparities. METHODS: Electronic Medical Record of 3,087 lymphomas (>18 years) were evaluated retrospectively, of which 842 (27%) patients were ≥65 years. Two hundred and twelve patients who were ≥65 years received first line treatment for DLBCL between May 2011 and Dec 2016. Demography, clinical features, associated co-morbidities, first line treatment outcomes and hospital costs were analysed. Patients were followed up till March 2020. RESULTS: The median age at presentation was 71 years. Gender ratio was 2.5:1. 38% patients presented with early-stage disease, 37% with low and low-intermediate International prognostic index, 49% with nodal disease. One or more co-morbidities were present in 58%. The commonest extra nodal site was gastro-intestinal (29%). Two-thirds of the patients presented with non-Germinal centre B subtype. The overall response (OR) to treatment was 72.5%. Patients who received anthracycline-based therapy (n = 124) and rituximab-based therapy (n = 159) had a median progression free survival (PFS), not reached and 47.0 months, respectively, versus 10 months and 7.9 months, respectively, for patients receiving non-anthracycline and non-rituximab therapies. At a median follow-up of 24 months, the 5-year overall survival and PFS are 44% and 41%, respectively, for the entire cohort. CONCLUSIONS: DLBCL is a curable lymphoma in elderly patients with standard anthracycline and rituximab-based therapies. Improvement in outcomes largely depends on social and financial support to complete the scheduled treatments.

Sequential Treatment of Arsenic Trioxide Followed by All Trans Retinoic Acid with Anthracyclines has Excellent Long-Term Cure in Acute Promyelocytic Leukemia.

Acute promyelocytic leukemia (APL) remains the most curable myeloid leukemia made feasible through effective use of two differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (ATO) with or without chemotherapy (CT). However, early morbidity and mortality remains a problem. With the objective of reducing early death a strategy of sequential induction ATO followed by consolidation ATRA in combination with CT was adopted by our group. The long-term outcomes of patient of APL treated on this sequential approach at our center was analyzed. In this retrospective analysis of prospectively maintained database consecutive adult patients with APL irrespective of their Sanz risk group were treated using a protocol of ATO (10 mg IV infusion over 3 h daily for 45 days) in the first phase followed by ATRA (45 mg/m2 for 60 days) in combination with Daunorubicin (60 mg/m2 for 3 days × 3 cycles) in second phase. All patients received maintenance ATRA (45 m/m2 for 15 days every 3 months) for a period of 18 months in phase 3. Patients were monitored for cytogenetic and molecular responses after phase 1 and 2. All patients were followed up for toxicity, event free and overall survival. 131 consecutive patients were treated in this study. At a median follow up of 60 months, 84.81% patients are alive with an overall event free survival (EFS) of 77.82%. Sanz low risk patients fared better (85%) versus intermediate and high-risk patients who had a 76% EFS. Proportion of patients alive at last follow up were 100% in Sanz low risk group and 82% in intermediate and high-risk group. The sequential schedule showed excellent tolerance and toxicity profile when treating newly diagnosed APL. The long-term follow-up data shows comparable if not better survival compared with the published real-world data and this has been consistent across all risk group.

Relapsed plasmablastic lymphoma in a HIV-negative patient: Pushing the envelope.

This case emphasizes that, with the availability of novel immunotherapy agents (Daratumumab), and repurposed use of bortezomib, a patient with HIV-negative relapsed PBL can be treated successfully and consolidated with an allogeneic haploidentical hematopoietic cell transplantation.

Relapsed Refractory Hodgkin Lymphoma and Brentuximab Vedotin-Bendamustine Combination Therapy as a Bridge to Transplantation: Real-World Evidence From a Middle-Income Setting and Literature Review.

INTRODUCTION: Despite high cure rates with standard treatment, 30% patients with Hodgkin lymphoma develop relapsed or refractory (R/R) disease. Salvage therapy followed by autologous hematopoietic cell transplantation (HCT) is considered standard of care. Brentuximab Vedotin (Bv) in combination with Bendamustine (B) has been tested in the salvage setting with promising results. MATERIALS AND METHODOLOGY: We conducted a single centre retrospective chart review of patients who received BBv salvage therapy to determine its activity and safety in patients with R/R classical Hodgkin lymphoma (HL). Between May 2011- December 2019, 179 patients were diagnosed with R/R HL. RESULTS: Thirty patients received BBv [median age: 30 (15-59) years, females (n=15)]. Primary refractory disease in 19 patients (63%), and 26 patients (87%) had advanced stage at treatment. Most patients received BBv after 2 prior lines of therapy [n=16 (53%)]. The median number of cycles of BBv were 3 (1-6). The number of BBv cycles delivered as outpatient was 63%. The most common Grade III/IV hematological adverse event was neutropenia [n=21, (70%)], while grade III/IV non-hematological toxicities included infections in 4 (13%), neuropathy in 4(13%), skin rash in 2 (7%), GI toxicities in 3 (10%) and liver dysfunction in 2 (7%) patients. The ORR and CR rates were 79% and 62%, respectively. Seventeen patients (57%) underwent an autologous HCT and 8 (26%) underwent an Allogeneic HCT (all haploidentical). The median follow up time from BBv administration was 12 months. Six patients died: 2 = disease progression, and 4 = non-relapse causes (Infection and sepsis = 2, GVHD=2). In addition to this, one patient progressed soon after HCT and another patient relapsed 22 months post HCT. Three year Overall survival (OS) and Event free survival (EFS) probability post-BBv treatment was 75% and 58%, respectively. OS and EFS analysis based on response (viz., CMR) to BBv demonstrated that patients in CMR had better survival probability [93% (p=0.0022) 3yr-OS and 72% (p=0.038) 3yr-EFS probability]. CONCLUSIONS: BBv is an active and well-tolerated salvage treatment for patients with R/R HL, even in refractory and advanced settings. In middle-income settings, cost constraints and access determine patient uptake of this regimen.

Diffuse Large B-Cell Lymphoma: Clinical Presentation and Treatment Outcomes From the OncoCollect Lymphoma Registry.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the commonest subtype of lymphoma, standard CHOP was the treatment of choice, 42% of patients received rituximab, and 29% of patients were lost to follow-up during therapy, were reported in a study that collected retrospective data at 13 public and private hospitals for patients diagnosed with lymphoma between January 2005 and December 2009. The OncoCollect Registry was set up in 2017 to address the challenges in the collection of retrospective data through chart review, recording access to anthracycline and rituximab-based treatment, and to study outcomes and any improvement in the patient follow-up. METHODOLOGY: The OncoCollect Lymphoma group registry was set up at a national level with 9 participating centers. Lymphoma patients registered at these centers between 2011 and 2017 were included. The clinical features, prognostic stratification, associated comorbidities, response to first-line treatment, and 3-year outcomes of adult patients with DLBCL were analyzed. RESULTS: Of the 5,886 lymphoma patients registered in the OncoCollect registry, 2,581 (44%) had DLBCL. A total of 1,961 were evaluable for frontline therapy. The median age at presentation was 57 years. Gender ratio was 1.6:1. At presentation, 43% were early stage, 70% had low and low intermediate IPI, 53% had extranodal disease, and 30.9% had one or more comorbidities (data available for 1,136 patients). The commonest extra nodal site was gastro-intestinal (23.98%) followed by head and neck (19.24%). The overall response rate was 79.29%. Complete remission was seen in 61.75%, partial response in 17.5%, stable disease in 4.3%, and progression in 7.9%. Patients who received anthracycline-based therapy (86.7%) and rituximab-based therapy (83.7%) had a 3-year event-free survival (EFS) of 69.67% and 68.48%, respectively. With a median follow-up of 33 months, the 3-year overall Survival (OS) and EFS were 75.37% and 66.58%, respectively. CONCLUSIONS: DLBCL remains the commonest (44%) lymphoma subtype and is curable with standard anthracycline- and rituximab-based therapies. The availability of rituximab has increased the proportion of patients receiving standard chemoimmunotherapy.

Real-World Outcomes of Hodgkin Lymphoma: A Multi-Centric Registry From India.

BACKGROUND: Hodgkin's lymphoma (HL) is one of the most curable malignancies with a 5-year survival of over 80%. Most published literature from low-middle income countries comes from single institute experience. METHODOLOGY: The OncoCollect Lymphoma group registry was set up in 2017 and has 9 major participating sites across India. Data of newly diagnosed classical HL (CHL) patients, treated between 2011 and 2017, were collected using OncoCollect software. The clinical features, subtypes, prognostic stratification, treatment patterns, response to first-line treatment, and 5-year outcomes were analyzed. All statistical analysis was done using Microsoft R Open statistical software linked to OncoCollect software. RESULTS: There were 939 newly diagnosed CHL patients with a median age of 38 (range, 18-99) years at presentation. The male-to-female ratio was 2.07:1. Histological subtypes included mixed cellularity, CHL (MC, CHL), nodular sclerosis, CHL (NS, CHL), lymphocyte-rich, CHL (LR, CHL), and lymphocyte-depleted, CHL (LD, CHL), in 60.60%, 26.94%, 9.80%, and 2.66%, respectively. At presentation, 50.43% had B symptoms and 53.35% had advanced disease. 29.71% of advanced-stage patients had high Hodgkin IPI score. 79% and 21% of patients received 1st-line treatment with chemotherapy alone or combined modality treatment with chemotherapy and radiotherapy. The most common first-line chemotherapy was ABVD-based regimen (94.68%). The overall response rate was 93.48%. Complete response rates among early-stage favorable and unfavorable risk groups were 92.73% and 86.79%, and those among advanced-stage low- and high-risk groups were 76.64% and 69.78%, respectively. The median relapse-free follow-up duration was 51 months (IQR 22-69). A significant difference was found in 5-year EFS between the early- and advanced-stage disease 83.53% and 73.55% (p = 0.00087), respectively. Similarly, significant difference was found in EFS among early-stage patients treated with a combination of 4-cycle chemotherapy and radiotherapy vs. chemotherapy alone 88.57% and 66.33% (p = 0.0042), respectively. CONCLUSIONS: In this large cohort from India, survival of patients with HL was comparable to the developed world. With a median follow-up of 51 months, the 5-year EFS and OS of all patients were 78.24% and 83.63%, respectively.

Impact of COVID-19 on peripheral stem cell collection and preservation at a hematopoietic cell transplant center in India: Experience 2020.

The prevailing corona virus disease 19 (COVID-19) pandemic has adversely affected the healthcare services globally. Hematopoietic cell transplantation (HCT) is considered as the preferred treatment option for several hematological malignancies, and HPC collection facilities have to function continuously along with implementing safety measures. Based on the national and international guidelines, we implemented additional measures and modifications to our standard operating procedure (SOP) to ensure secure HPC collection from patients as well as donors. Here, we report our experience with HPC collection and processing from 1st January, 2020 until 31st December, 2020. We collected 59 HPC products through apheresis and 41 cryopreservation procedures. Compared to 2019, there was a 33% decrease in the number of HPC transplants and 31% reduction in HPC collection procedures. However, we report an 86% (13 procedures) increase in the cryopreservation of HPC products from related donors, as several organizations recommend cryopreservation of HPC products. We report our institutional experience to better understand the impact of COVID-19 on HCT services in a tertiary care center in the developing world. It may also help in being prepared for any future waves of COVID-19 cases.

COVID-19 and haematology services in a cancer centre from a middle-income country: adapting service delivery, balancing the known and unknown during the pandemic.

The COVID-19 pandemic has caused major disruptions in multiple spheres of healthcare delivery in the world. Developing nations have had to tackle this unanticipated crisis in the midst of various other healthcare delivery issues and resource constraints. As a tertiary level cancer care provider located in an eastern Indian city, a COVID-19 hotspot, we share our experience from the perspective of haematology and haematopoietic stem cell transplantation (HSCT) services. The primary challenges related to infection control included infection screening and decreasing exposure among patients and healthcare workers. Logistic challenges include maintaining essential patient care services, personnel redeployment, blood bank inventory constraints and maintaining the supply chain for a continuum of care. Clinical management challenges were dealt with by rationalising treatment delivery by modification of treatment regimens, risk-based deferral of HSCT, management of COVID-19 in patients, and staggering the follow-up schedules in survivors and those on maintenance therapies, among other strategies. These challenges were compounded by the restrictions imposed by a countrywide lockdown in the initial period of the pandemic, which also affected the socio-economic aspects of treatment delivery. As a training institution, this period also impacted academics and research activities. This overview details our response to these challenges during the COVID-19 pandemic, which has many unknowns.

Gender climate in Indian oncology: national survey report.

INTRODUCTION: There is evidence of under-representation of women in leadership roles and publications in oncology. However, there is little knowledge about their perceptions of professional environment, unique challenges and opportunities compared with male counterparts. The problem is more prominent in lower-income and middle-income countries like India and merits exploration. MATERIALS AND METHODS: A survey, 'Exploratory Study on the Challenges of Female Oncologists in India', was conducted among oncology professionals. We included questions on demography, working team details, role at work, perceived challenges for advancement of career, gender-related values brought into the team and the measures for improvement of gender disparity. Lead authorship data were collected from two Indian oncology journals. RESULTS: Of the 324 respondents, 198 (61.1%) were women. Majority of the respondents were medical oncologists (46.3%), ≤45 years old (69.4%) and working in universities and corporate hospitals (71.6%). One hundred eighty-nine (58.3%) respondents worked in teams with male majority, 50 (15.4%) in women-majority teams, while 85 (26.2%) worked in teams with gender equality. Of the 324 respondents, 218 (67.3%) had men managers, while 106 (32.7%) had women managers. Men led 160 (84.7%) male-majority teams; 45 (52.9%) gender-equal teams; and 13 (26%) female-majority teams (p<0.00001). Age >45 years was found to be associated with a leadership role (43% vs 25%, p=0.0012). The most significant barrier perceived for advancement of career for women was finding a work-life balance. Most respondents suggested provision of flexible training programmes to improve the disparity. Of the 558 journal publications inspected, 145 (26%) articles had a female first or corresponding author. CONCLUSIONS: The study brought out the current figures regarding gender climate in oncology practice and academia across India. We identified lead thrust areas and schemes to improve the gender bias. There needs to be action at international, national and personal levels to bring about an efficient gender-neutral workforce.